Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells Capillarization in Carbon Tetrachloride-Induced Rats Fibrosis.

Abstract Background: Qizhu granule, a traditional Chinese medicine, has been widely used in clinic as a complementary and alternative medicine to treat liver fibrosis.However, the mechanism underlying its anti-hepatic fibrosis is still not clear. Liver fibrosis accompanied by liver sinusoidal pathological angiogenesis has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. In this study, we investigated the mechanism of anti-capillarization of this herbal drug against liver fibrosis.Materials and methods: The liver fibrosis rats model induced by 4-week of intervention with 40% CCl4 was employed in this study. Meanwhile, low, medium and high dose serum containing Qizhu granules were prepared. Liver tissues were acquired, and liver samples were subjected to histological studies.LSECs were isolated from liver fibrosis rats and were routinely cultured for 48h in low, medium and high dose of Qizhu granules-containing serum. The fenestration of LSECs in liver fibrosis rats were observed under scanning electron microscopy. The expression of the endothelial cell surface markers CD31, SE-1 and LSECs integrin ɑVβ3, FAK, p-FAK, Ras, MAPK, p-MAPK were measured by western blot.Results: Compared with the control group, the loss of fenestration of LSECs in the model group increased. After intervention of Qizhu granule-containing serum, the fenestration of the structure of LSECs in liver fibrosis induced by CCl4 increased, especially in the high-dose Qizhu granules group. ompared with the control group, the expression levels of SE-1 and CD31 in LSECs in the model group were significantly increased (P < 0.05). Compared with the model group, the expression levels of SE-1 and CD31 in LSECs of rats with hepatic fibrosis induced by CCl4 decreased after the treatment of low, medium and high dose serum containing Qizhu granules (P < 0.05). Among them, the expression levels of SE-1 and CD31 in LSECs of Qizhu granules group decreased with the increase of dosage, showing a dose-dependent relationship to a certain extent. Compared with the normal control group, the expression of integrin ɑVβ3, Ras, p-FAK and p-MAPK protein increased in the LSECs of model group(P <0.05). After treatment with Qizhu granule-containing serum, the expression of integrin ɑVβ3, p-FAK and p-MAPK protein in LSECs of liver fibrosis rats induced by CCl4 were reduced (P <0.05), and the expression of FAK, Ras and MAPK protein decreased ( P> 0.05).Conclusions: Qizhu granule could reduce the loss of fenestration of LSECs, transforming the cell phenotype of LSECs, and ameliorating the pathological remodeling of hepatic sinus capillarization in hepatic fibrosis induced by CCl4 in rats. It was found that Qizhu granules played an anti-fibrosis role by suppressing the expression of integrin ɑVβ3-FAK-Ras/MAPK signaling pathway of LSECs in CCl4-induced fibrosis rats.

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Experimental Study Oviductus ranae for the Change of α-SMA and TGF-β in Hepatic Fibrosis Rat Liver

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.912-914.1940 ◽

2014 ◽

Vol 912-914 ◽

pp. 1940-1943

Author(s):

Yan Li ◽

Xiao Ou Li ◽

Feng Hao ◽

Lei Zhang ◽

Lei Liu ◽

...

Keyword(s):

Liver Fibrosis ◽

Hepatic Fibrosis ◽

Rat Liver ◽

Liver Tissue ◽

Female Rats ◽

Control Group ◽

Group Model ◽

Model Group ◽

Model Control ◽

Oviductus Ranae

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.

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In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.613784 ◽

2021 ◽

Vol 8 ◽

Author(s):

Huilong Fang ◽

Ling Yu ◽

Da You ◽

Nan Peng ◽

Wanbei Guo ◽

...

Keyword(s):

Liver Fibrosis ◽

Mrna Expression ◽

Hepatic Fibrosis ◽

Inflammatory Factors ◽

Control Group ◽

Therapeutic Effects ◽

Type I ◽

Expression Levels ◽

Tnf Α ◽

Mrna Expression Levels

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

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Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease

Open Chemistry ◽

10.1515/chem-2019-0145 ◽

2019 ◽

Vol 17 (1) ◽

pp. 1328-1338

Author(s):

Yufeng Xing ◽

Chuantao Zhang ◽

Fenfen Zhai ◽

Tianran Zhou ◽

Xiang Cui ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver Disease ◽

Dose Group ◽

Control Group ◽

High Dose ◽

Model Group ◽

Alcoholic Fatty Liver ◽

Oil Red O Staining ◽

Alcoholic Fatty Liver Disease ◽

Oil Red O

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.

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Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

European Journal of Inflammation ◽

10.1177/20587392211000896 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110008

Author(s):

Meng Chen ◽

Xinyan Song ◽

Jifang Jiang ◽

Lei Xing ◽

Pengfei Wang

Keyword(s):

Carbon Tetrachloride ◽

Liver Toxicity ◽

Corn Oil ◽

Histopathological Examination ◽

Hepatoprotective Effect ◽

Control Group ◽

Group Model ◽

Protective Effects ◽

Model Group ◽

Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

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Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway

International Journal of Endocrinology ◽

10.1155/2020/9725898 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Fangui Zhao ◽

Wenjun Wang

Keyword(s):

Ovarian Reserve ◽

Low Dose ◽

Control Group ◽

High Dose ◽

Model Group ◽

Menopausal Syndrome ◽

Primordial Follicles ◽

Akt Phosphorylation ◽

Vinylcyclohexene Diepoxide ◽

Sd Rats

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.

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Therapeutic Effect of Glycyrrhizin Arginine Salt on Rat Cholestatic Cirrhosis and its Mechanism

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500581 ◽

2018 ◽

Vol 46 (05) ◽

pp. 1111-1127 ◽

Cited By ~ 2

Author(s):

Huan Zhang ◽

Yajun Lin ◽

Yongzhan Zhen ◽

Gang Hu ◽

Xu Meng ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Therapeutic Effect ◽

Group Treatment ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Water Model ◽

Control Group ◽

High Dose ◽

Model Group ◽

Duct Ligation

To investigate the therapeutic effect of glycyrrhizin arginine salt on rat cholestatic cirrhosis, we subjected male Sprague Dawley rats to common bile duct ligation for 14 days and treated them with distilled water (model group), arginine, or a low or high dose of glycyrrhizin arginine salt by gavage. A sham-operated group was used as a control group. Treatment with glycyrrhizin arginine salt substantially improved animal growth rates, reduced the ratio of liver weight to body weight and decreased total bilirubin, aspartate aminotransferase, 8-isoprostane and malondialdehyde compared with the values measured in the model group. The progress of liver fibrosis, as detected by hematoxylin and eosin and Masson’s trichrome staining, was slower in the glycyrrhizin arginine salt groups than in the model group or the arginine group. Reductions of bile salt pool size, hepatic hydroxyproline content and fibrosis score were also seen in the glycyrrhizin arginine salt groups compared with the model group. Furthermore, glycyrrhizin arginine salt significantly reduced the expression of transforming growth factor [Formula: see text]1 (TGF-[Formula: see text]1), [Formula: see text]-smooth muscle actin, tumor necrosis factor-[Formula: see text] and matrix metalloproteinases 2 and 9. Glycyrrhizin arginine salt also inhibited the expression of [Formula: see text]-SMA and matrix metalloproteinases 2 and 9 in response to TGF-[Formula: see text]1 in LX-2 cells and primary rat hepatic stellate cells and mitigated the cytotoxicity induced by rat bile in HepG2 cells and primary rat hepatocytes.

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Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

10.21203/rs.3.rs-101537/v1 ◽

2020 ◽

Author(s):

Wenjun Shi ◽

Fei Yang ◽

Liting Wang ◽

Nankun Qin ◽

Chengxiang Wang ◽

...

Keyword(s):

Male Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

High Dose ◽

Intragastric Administration ◽

Group Model ◽

Model Group ◽

Tnf Α ◽

Plantaginis Semen ◽

Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

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Dynamic Changes in MMP1 and TIMP1 in the Antifibrotic Process of Dahuang Zhechong Pill in Rats with Liver Fibrosis

Open Chemistry ◽

10.1515/chem-2019-0041 ◽

2019 ◽

Vol 17 (1) ◽

pp. 346-356

Author(s):

Jiayu Lin ◽

Chaowen Deng ◽

Yanzhong Peng ◽

Jie Zheng ◽

Liya Wei ◽

...

Keyword(s):

Treatment Group ◽

Liver Fibrosis ◽

Differentially Expressed ◽

Tissue Inhibitor Of Metalloproteinase ◽

Control Group ◽

Model Group ◽

Sprague Dawley ◽

Dynamic Changes ◽

Matrix Metalloproteinase 1 ◽

Liver Tissues

AbstractOn the basis of carbon tetrachloride (CCl4)induced liver fibrosis in rats, this study aims to investigate the dynamic changes in matrix metalloproteinase 1 (MMP1) and the tissue inhibitor of metalloproteinase 1 (TIMP1) in the antifibrotic process of Dahuang Zhechong Pill (DHZCP). A total of 50 male Sprague Dawley rats, aged 8 weeks, were randomly divided into 3 groups: the control group, the model group (the group treated with CCl4), and the treatment group (the group treated with CCl4 and DHZCP). Rats were sacrificed at Weeks 4 and 8. Liver tissues were separated for RNA sequencing and bioinformatics analysis. Real-time PCR, Western blot analysis, and histological staining were conducted to confirm the gene expression and pathological change in liver tissues. Compared with control group, rats in model group showed poor mental state and slow weight gain. The liver tissues of the rats in the model group exhibited a damaged hepatic lobule structure, fibrous connective tissue hyperplasia, and inflammatory cell infiltration among the hyperplastic tissues. DHZCP could significantly improve the appearance of rats and alleviate CCl4-induced fibrosis. Compared to model group, 798 differentially expressed mRNAs were found in the treatment group, of which 120 were up-regulated and 678 were down-regulated. Differentially expressed mRNAs between the CCl4-induced group and the DHZCP-treated group were mainly focused on the following KEGG pathways: focal adhesion, phagosome, tight junction, and ECM–receptor interactions. Relative to those in the control group, MMP1 was downregulated, whereas, TIMP1 and Col1A1 were upregulated in the CCl4-induced group at Weeks 4 and 8. DHZCP could reverse MMP1, TIMP1, and Col1A1 expression.DHZCP protects against liver injury and exerts an antifibrotic effect on liver fibrosis induced by CCl4 in rats. Its mechanism may be related to the upregulation of MMP1, downregulation of TIMP1, and promotion of collagen degradation.

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Effects of Chaihu-Shugan-San and Shen-Ling-Bai-Zhu-San on p38 MAPK Pathway in Kupffer Cells of Nonalcoholic Steatohepatitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/671013 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Qin-He Yang ◽

Yong-Jian Xu ◽

Yi-Zhen Liu ◽

Yin-Ji Liang ◽

Gao-Fei Feng ◽

...

Keyword(s):

P38 Mapk ◽

Kupffer Cells ◽

Mapk Pathway ◽

Inflammatory Factors ◽

High Dose ◽

Model Group ◽

Expression Levels ◽

Treatment Groups ◽

P38 Mapk Pathway ◽

All Treatment

This study aimed to investigate the effects of Chaihu-Shugan-San (CSS), Shen-Ling-Bai-Zhu-San (SLBZS), and integrated recipe of the above two recipes on inflammatory markers and proteins involved in p38 MAPK pathway in Kupffer cells of NASH rats induced by high fat diet (HFD). Rats were administered at low or high dose of CSS, SLBZS, and integrated recipe except normal group and model group for 16 weeks. The levels of hepatic lipid, TNF-α, IL-1, and IL-6 in liver tissues were measured. Kupffer cells were isolated from livers to evaluate expressions of TLR4, p-p38 MAPK, and p38 MAPK by Western blotting. The results showed that the NASH model rats successfully reproduced typical pathogenetic and histopathological features. Levels of hepatic lipid and liver tissues inflammatory factors in high-dose SLBZS group and integrated recipe group were all lower than that of model group decreased observably. Expressions of TLR4, p-p38 MAPK, and p38 MAPK in Kupffer cells were decreased in all treatment groups, but there was no significant difference between treatment groups. The high-dose SLBZS group had the lowest expression levels of TLR4, and the most visible downtrend in the expression levels of p-p38 MAPK and p38 MAPK was found in the high-dose integrated recipe group. The ratio of p-p38 MAPK to total p38 MAPK protein was obviously increased in all treatment groups. Therefore, our study showed that the activation of p38 MAPK pathway in Kupffer cells might be related to the release of inflammatory factors such as TNF-α, IL-1, and IL-6 in NASH rats. High dose of SLBZS and integrated recipe might work as a significant anti-inflammatory effect in Kupffer cells of NASH rats induced by HFD through suppression of p38 MAPK pathway. It indicated that p38 MAPK pathway may be the possible effective target for the recipes.

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Melatonin pretreatment can improve the therapeutic effect of Adipose-derived Stem Cells on CCl4-induced liver fibrosis

10.21203/rs.3.rs-868703/v1 ◽

2021 ◽

Author(s):

Ziqiang Zhang ◽

Yingying Sun ◽

Haojie Wang ◽

Yuxiang Yang ◽

Ruiqi Dong ◽

...

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Therapeutic Effect ◽

Control Group ◽

Group Model ◽

Adipose Derived Stem Cells ◽

Model Group ◽

Nuclear Fragmentation ◽

Apoptotic Genes ◽

And Control

Abstract Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.

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