scholarly journals Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

2020 ◽  
Author(s):  
Qi Zhang ◽  
Zheng Shu-guang ◽  
Wang Bao-juan ◽  
Wang Lin ◽  
Li Tian-yang
Keyword(s):  
Treatment Group ◽  
Signaling Pathway ◽  
Toluidine Blue ◽  
Quantitative Polymerase Chain Reaction ◽  
Blue Staining ◽  
High Dose ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Model Group ◽  
Cxcr4 Signaling

Abstract Background To determine whether Guyanxiao formula protects chondrocytes in a model of knee arthritis induced by lipopolysaccharide, and whether it can repair chondrocyte damage and suppress osteoarthritis cartilage degeneration by regulating SDF-1 / CXCR4 signaling pathway.Methods Lipopolysaccharide(LPS) induces chondrocytes in vitro to prepare knee osteoarthritis model. Toluidine blue (TBS) staining was used to observe the changes of proteoglycan content of rabbit chondrocytes in order to identify the source of cells. The biochemical detection method was used to determine the content of inflammatory factor nitric oxide (NO) in chondrocytes to identify whether the osteoarthritis chondrocytes were successfully modeled in vitro.The cell proliferation rate was measured by the cell viability test (CCK-8), the concentration with no obvious cytotoxicity was screened, and the low, medium and high dose groups of Guyanxiao formula were established.Immunofluorescence(IF) staining was used to observe the effect of Guyanxiao formula on the content of type Ⅱ collagen in chondrocytes of knee osteoarthritis.Enzyme-linked immunosorbent assay was carried out to determine the expression of inflammatory factors MMP-3, MMP-9 and MMP-13. The mRNA and protein expressions of SDF-1, CXCR4, Vascular endothelial growth factor(VEGF) were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis.Results The identify of chondrocytes was confirmed with toluidine blue staining. LPS treatment remarkably increased the NO content, indicating successful noodling of the KOA chondrocyte model. According to the CCK-8 experiment results, 0.36, 3.6, and 36 µg / mL were set as the low, medium, and high dose administration concentrations of ostitis.Immunofluorescence(IF) staining showed that the degree of type Ⅱ collagen damage in each treatment group was improved compared with the model group, and the high concentration group was the most obvious improvement in the Guyanxiao formula treatment group.The levels of MMP-3,MMP-9, MMP-13, and IL-1b were much lower in the Cell supernatant of the each treatment group than in that of model group.The levels of SDF-1, CXCR4, VEGF mRNA and protein were much lower in the Chondrocytes of the each treatment group than in that of model group. In addition, the therapeutic effect of Guyanxiao formula treatment group decreased in a concentration-dependent manner.Conclusion Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway.

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

Ulinastatin Activated The ERK5/Mer Signaling Pathway To Promote Macrophage Efferocytosis And Ameliorate Lung Inflammation

2021 ◽  
Author(s):  
Jinju Li ◽  
Rongge Shao ◽  
Qiuwen Xie ◽  
XueKe Du
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Anti Inflammatory

Abstract Purpose:Ulinastatin (UTI) is an endogenous protease inhibitor with potent anti-inflammatory, antioxidant and organ protective effects. The inhibitor has been reported to ameliorate inflammatory lung injury but precise mechanisms remain unclear. Methods: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). The number of neutrophils and the phagocytosis of apoptotic neutrophils were observed by Diff- Quick method. Lung injury was observed by HE staining .BALF cells were counted by hemocytometer and concentrations of protein plus inflammatory factors were measured with a BCA test kit. During in vitro experiments, RAW264.7 cells were pretreated with UTI (1000 and 5000U/ mL), stained with CellTrackerTM Green B0DIPYTM and HL60 cells added with UV-induced apoptosis and PKH26 Red staining. The expression of ERK5\Mer related proteins was detected by western blot and immunofluorescence.Results: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). UTI treatment enhanced the phagocytotic effect of mouse alveolar macrophages on neutrophils, alleviated lung lesions, decreased the pro-inflammatory factor and total protein content of BALF and increased levels of anti-inflammatory factors. in vitro experiments ，UTI enhanced the phagocytosis of apoptotic bodies by RAW264.7 cells in a dose-dependent manner. Increased expression levels of ERK5 and Mer by UTI were shown by Western blotting and immunofluorescence.Conclusions: UTI mediated the activation of the ERK5/Mer signaling pathway, enhanced phagocytosis of neutrophils by macrophages and improved lung inflammation. The current study indicates potential new clinical approaches for accelerating the recovery from lung inflammation.

scholarly journals Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

2018 ◽  
Vol 48 (3) ◽  
pp. 971-982 ◽  
Author(s):  
Yang  Cheng ◽  
Tianyang Chen ◽  
Jian Ping ◽  
Jianjie Chen
Keyword(s):  
Treatment Group ◽  
Palmitic Acid ◽  
Inflammatory Cytokines ◽  
Kupffer Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Lipid Accumulation ◽  
Hepatic Injury ◽  
High Dose ◽  
Therapeutic Effects ◽  
Dependent Manner

Background/Aims: Nonalcoholic steatohepatitis (NASH) is defined as lipid accumulation with hepatic injury, inflammation and early to moderate fibrosis. Kupffer cells play a crucial role in promoting hepatic inflammation, which further facilitates the development of NASH. Here we investigated the effects of Cangju Qinggan Jiangzhi decoction (CQJD) on high fat diet (HFD) and methionine-choline deficient (MCD) induced mouse NASH pathogenesis. Methods: Mouse NASH models were developed by HFD and MCD diet. The treated mice were divided into three groups: the control group (n = 10), the low-dose CQJD treatment group (n = 10) and the high-dose CQJD treatment group (n = 10). The hepatic injury, inflammation, and apoptotic molecules were evaluated by H&E staining, immunohistochemistry and real-time PCR. Kupffer cells were isolated from control mice and CQJD-treated mice after stimulation by lipopolysaccharide (LPS) and/or palmitic acid. The level of the inflammatory cytokines TNFα, IL1β, and CCL2 was measured by ELISA. Results: The HFD-fed mice displayed significant metabolic, inflammatory, and oxidative stress-related alterations due to hepatic lipid accumulation. CQJD treatment largely normalized the hepatic injury, lowered the ALT/AST level, and reduced the severity of liver inflammation, as revealed by the decreased inflammatory cytokines levels. In vitro, CQJD blocked the activation of LPS- or palmitic acid-primed Kupffer cells in a dose-dependent manner. In the MCD diet-induced NASH mice, similar therapeutic effects of CQJD were also observed. Conclusion: CQJD ameliorates mouse nonalcoholic steatohepatitis. The reduction in liver injury and inflammation induced by CQJD is associated with reduced activation of Kupffer cells. Our results suggest that CQJD is a promising therapeutic strategy in clinical steatohepatitis.

scholarly journals Tangzhiqing Granules Alleviate Podocyte Epithelial-Mesenchymal Transition in Kidney of Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Haiyan Xu ◽  
Xu Wang ◽  
Mingming Liu ◽  
Xueyuan He
Keyword(s):  
Molecular Markers ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Rats ◽  
High Dose ◽  
Mesenchymal Transition ◽  
Dose Treatment ◽  
Smad Signaling ◽  
Smad Signaling Pathway

This study discussed the effect of Tangzhiqing granules on podocyte epithelial-mesenchymal transition in kidney of diabetic rats. The diabetic rats were divided randomly into five groups: DM group treated with vehicle, Tangzhiqing granules low-dose treatment group, Tangzhiqing granules middle-dose treatment group, and Tangzhiqing granules high-dose treatment group. Eight Wistar rats used as control group were given saline solution. The intervention was all intragastric administration for 8 weeks. At the end of the 8 weeks, biochemical parameters and kidney weight/body weight ratio were measured. The kidney tissues were observed under light microscope and transmission electron microscopy. To search for the underlying mechanism, we examined the epithelial-to-mesenchymal transition (EMT) related molecular markers and TGF-β/smad signaling pathway key proteins expression. The results showed that Tangzhiqing granules relieved the structural damage and functional changes of diabetic kidneys. Kidney podocyte EMT related molecular markers nephrin and CD2AP expression were increased, when desmin and α-SMA levels were decreased by Tangzhiqing granules in diabetic rats. Further TGF-β/smad signaling pathway key proteins TGF-β1 and p-smad2/3 levels were decreased in diabetic rats after treatment with Tangzhiqing granules. These findings suggest that Tangzhiqing granules may protect the podocytes of diabetic nephropathy rats via alleviating podocyte EMT and likely activating TGFβ/smad signaling pathway.

scholarly journals Effect of Erdosteine on Middle Ear Effusion in Rats by Mediating TLR4 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Te Li ◽  
Wanting Zeng ◽  
Rongrong Liu
Keyword(s):  
Treatment Group ◽  
Signaling Pathway ◽  
Otitis Media ◽  
Middle Ear ◽  
Middle Ear Effusion ◽  
Model Group ◽  
Tlr4 Signaling ◽  
Expression Levels ◽  
Tlr4 Signaling Pathway ◽  
Ear Effusion

The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, n = 15 ) and erdosteine treatment group (18 mg/kg, gavage, treatment group, n = 15 ). Besides, a normal group ( n = 15 ) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-β) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased ( p < 0.05 ). Besides, the content of MPO, MMP, and TNF-β was overtly raised in the model group ( p < 0.05 ), while it was notably lowered in the treatment group ( p < 0.05 ). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.

scholarly journals DPP4 inhibitors promote biological functions of human endothelial progenitor cells by targeting the SDF-1/CXCR4 signaling pathway

2016 ◽  
Vol 68 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Feng Liu ◽  
Guo-Dong Huang ◽  
Jia-Zhen Tang ◽  
Yu-Huan Peng
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Hypoglycemic Agents ◽  
Dependent Manner ◽  
Biological Functions ◽  
Endothelial Progenitor ◽  
Cxcr4 Signaling ◽  
Dpp4 Inhibitors

Dipeptidyl peptidase 4 (DPP4) inhibitors(oral hypoglycemic agents)have beneficial effects during the early stages of diabetes. In this study, we evaluated the role of DPP4inhibitorsonthe biological functions of cultured human endothelial progenitor cells (EPCs). After treating EPCs with the DPP4 inhibitors sitagliptin and vildagliptin, we examined the mRNA expression of DPP4, vascular endothelial growth factor (VEGF),VEGF receptor 2 (VEGFR-2),endothelial nitric oxide synthase (eNOS), caspase-3,stromal cell-derived factor-1 (SDF-1), chemokine (C-X-C motif) receptor 4 (CXCR4) were measured by RT-PCR. The protein expression of SDF-1 and CXCR4 was determined by Western blot; cell proliferation was tested by the MTT method, and DPP4 activity was determined by a DPP4 assay. Our results revealed that DPP4 expression and activity were inhibited following the treatment with various doses of DPP4 inhibitors. Cell proliferation and the expression of VEGF, VEGFR-2andeNOS were up regulated, while cell apoptosis was inhibited by DPP4 inhibitors in a dose-dependent manner. DPP4 inhibitors activated the SDF-1/CXCR4 signaling pathway, shown by the elevated expression of SDF-1/CXCR4. This further proved that after the SDF-1/CXCR4 signaling pathway was blocked by its inhibitor ADM3100, the effects of DPP4 inhibitors on the proliferation and apoptosis, and the expression of VEGF, VEGFR-2and eNOS of EPCs were significantly reduced. These findings suggest that DPP4 inhibitors promote the biological functions of human EPCs by up regulating the SDF-1/CXCR4 signaling pathway.

scholarly journals L-Asparaginase-Induced Allergy in Mice: Effects of Concomitant Drugs and Anti-IgE Antibody

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1632-1632 ◽  
Author(s):  
Ai Nogami-Hara ◽  
Kazuki Hara ◽  
Yasuhiro Kawakami ◽  
Akira Shimada ◽  
Mitsunobu Mio
Keyword(s):  
Animal Model ◽  
Toluidine Blue ◽  
Lymphoblastic Leukemia ◽  
Intradermal Injection ◽  
Eosinophil Infiltration ◽  
Blue Staining ◽  
Type I ◽  
Dependent Manner ◽  
Ige Antibody ◽  
Type I Hypersensitivity

Abstract BACKGROUND: L-Asparaginase (L-Asp) derived from E. coliis one of the essential drugs for the treatment of acute lymphoblastic leukemia (ALL) and lymphoma. Native L-Asp often causes hypersensitivity reactions, including anaphylaxis, which account for termination and inferior outcome of L-Asp therapy of ALL. Since the characteristics of L-Asp-induced hypersensitivity are not well documented, there is neither suitable treatment for hypersensitivity to L-Asp nor animal model of L-Asp allergy. In addition, some anti-cancer drugs, used concomitantly with L-Asp, affect lymphocyte activities, the role of such drugs on L-Asp hypersensitivity is not known. Aims:In this study, we induced type I hypersensitivity to E. coliL-Asp in mice in order to investigate the mechanism and treatment of L-Asp allergy. Anti-IgE antibody, binding to Fc region of IgE to block the binding to FcεRI receptor, was used as a candidate for the treatment of L-Asp hypersensitivity. Furthermore, we examined the effects of methotrexate (MTX) and cyclophosphamide (CY). which reportedly impair the functions of Th17 and Treg cells, respectively. Methods: Male BALB/c mice (7 week old) were intraperitoneally injected L-Asp (10, 20, 100 IU/mouse) with Al (OH)3gel on days 0 and 14. The right ears of the mice were locally sensitized on days 17, 20, 23 by intradermal injection of L-Asp (1, 2, 10 IU/mouse). Antigen challenge was carried out on day 26 by intradermal injection of L-Asp. MTX (50, 100, 200 mg/kg) and CY (150 mg/kg) were intraperitoneally administrated on day -2 and day 12. On day 25, either anti-IgE antibody (50, 100 mg/mouse) or control IgG was intraperitoneally administered to the sensitized mice. The ear thickness was measured (n=6 or more). H&E and toluidine blue stainings of ear sections were performed. Results : L-Asp challenge immediately induced ear edema, in a dose-dependent manner. The reaction reached to a peak at 1 hr after stimulation (dosage: sensitization = 100 IU/mouse, challenge = 10 IU/mouse; edema thickness: 31.25±3.8 μm vs control 4.38±1.9 μm, p<0.01), which subsided within 24 hr. Microscopic observations showed eosonophil infiltration (H&E staining; 0.5±0.2 cells/HPF in control ears and 10.4±1.0 cells/HPF in challenged ears, P<0.001) and degranulation of mast cells (toluidine blue staining; 8.4±0.9 % in control ears and 47.6±5.8 % in challenged ear, P<0.001). Anti-IgE antibody significantly inhibited the ear swelling to 7.3±1.2 μm (P<0.01) as well as microscopic changes in eosinophil infiltration and mast cell degranulation. When the mice were treated with anticancer drugs prior to sensitization, the ear swellings were augmented by CY (43.54±4.0 μm, P<0.05) but not MTX (31.67±5.5 μm, not significant). Anti-IgE antibody also inhibited CY-augmented ear swelling. Conclusions: From these results, we firstly established animal model for type I hypersensitivity to L-Asp. Using this model, we conclude that non-anaphylactogenic neutralizing antibody of IgE, such as omalizumab, can be a candidate drug for the treatment of L-Asp hypersensitivity. Also, CY-induced suppression of Treg function may enhance Th2 responses so as to augment L-Asp hypersensitivity. Further investigations for the detection and avoidance of L-Asp hypersensitivity are under the way. Disclosures No relevant conflicts of interest to declare.

Effects of Cornu Bubali (CB) on the Adhesion of Leukocyte and Endothelial Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 554-561
Author(s):  
Haixia Li ◽  
Zhenghui Xiao ◽  
Xuefei Tian ◽  
Paoqiu Wang ◽  
Yan Long ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Notch Signaling Pathway ◽  
Dependent Manner ◽  
Qpcr Analysis ◽  
Tnf Α

Background: The interaction between leukocytes and vascular endothelial cells is ubiquitous in the occurrence and development of many diseases, especially in the body's defense response. The purpose of the present study was to investigate the effect of cornu bubali (CB) on the adhesion of leukocytes to endothelial cells. Materials and methods: Human leukemic cell line (HL-60) and human umbilical vein endothelial cells (HUVECs) were used to simulate the adhesion effect between cells. After HUVECs were treated with TNF- α(15 ng/mL) combined with different dose of CB (15, 30 and 60 μmol/L) and dexamethasone (DEX, 2 μg/ml) for 24 h, HL-60 cells were added into the coculture system for another 1 h. CCK8 assay was performed to investigate cell viability of HUVECs. HL-60 cells adhesion to HUVECs was quantified using Hoechst 33342 staining. Subsequently, the levels of adhesion molecules were detected by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. RT-qPCR and western blot were performed to assess the levels of inflammatory cytokines, chemokines and the expression of Notch signaling pathway. Results: Treatment with CB could reduce the adherence of HL-60 to HUVECs induced by TNF- in a dose-dependent manner. CB inhibited the expression of ICAM-1, VCAM-1, CD44, IL-1β, COX-2 and CCL4 in HUVECs. Western blot and RT-qPCR analysis confirmed that CB prevented TNF-α -induced over-expression of Notch receptors (Notch1 and Notch2), Notch ligands (DLL1 and Jagged1), signaling effectors (Hes1) and adhesion related proteins (NF-κB/p65, p-I B and IκBκ) in HUVECs. Conclusion: CB induces interactions between leukocytes and endothelial cells through the activation of Notch signaling pathway. These data contribute to further explain the protective effect of CB against development of inflammatory process of hemorrhage in acute leukemia.

Matrine Regulates Th1/Th2 Balance to Treat Eczema by Upregulating Interferon-γ

2020 ◽  
Vol 20 (6) ◽  
pp. 3378-3386 ◽  
Author(s):  
Ling Zhang ◽  
Sucai Lin ◽  
Yongping Zheng ◽  
Haitang Wang
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Skin Lesions ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Inflammatory Factor ◽  
Chain Reaction ◽  
Treatment Groups ◽  
Polymerase Chain ◽  
Effective Medication

Although matrine (C15H22N2O) has been confirmed to be an effective medication in the treatment of eczema, the mechanisms by which it does so are still unclear. In this study, the mechanisms by which matrine treats eczema were investigated by using oxymatrine, a matrine derivative, to treat guinea pigs with eczema. The differences between the treatment groups in this study were statistically significant (P < 0.05). We prepare nanoparticles to extract RNA. The results showed that the treatment with a high dose of oxymatrine (high-dose OMT) reduced the damage done by eczema to guinea pig skin tissue (i.e., skin lesions). The high-dose OMT inhibited the expression of pro-inflammatory factor proteins, as quantified by enzyme-linked immunosorbent assay (ELISA). The high-dose OMT also increased Th1 and CD4+TGFβ+ levels, as measured by flow cytometry. Examination of skin lesions showed that the high-dose OMT alleviated the symptoms of eczema. We used magnetic nanobeads to extract nucleic acids for detection with quantitative polymerase chain reaction (qPCR), and found that the high-dose OMT improved the expression of pro-inflammatory factor genes. Using western blot analysis, we also found that the high-dose OMT was able to regulate the expression levels of IFN-γ and TGF-β proteins. Our experimental results indicated that matrine treats eczema by upregulating IFN-γ and downregulating TGF-β levels to regulate the Th1/Th2 balance.

Effects of carvedilol on expression of TLR4 and its downstream signaling pathway in liver tissue of rats with cholestatic liver fibrosis

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiaopeng Tian ◽  
Huimin Zhao ◽  
Zengcai Guo
Keyword(s):  
Treatment Group ◽  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Liver Tissue ◽  
High Dose ◽  
Sham Operation ◽  
Downstream Signaling ◽  
Duct Ligation ◽  
Downstream Signaling Pathway

Objectives: This study was designed to investigate the effects of carvedilol on the expression of TLR4 and its downstream signaling pathway in liver tissue of rats with cholestatic liver fibrosis and provide experimental evidence for clinical treatment of liver fibrosis with carvedilol. Methods: A total of fifty male Sprague Dawley rats were randomly divided into five groups (10 rats per group): sham operation (SHAM) control group, bile duct ligation (BDL) model group, low-dose carvedilol treatment group (0.1mg•kg-1•d-1), medium-dose carvedilol treatment group (1mg•kg-1•d-1), and high-dose carvedilol treatment group (10mg•kg-1•d-1). Rat hepatic fibrosis model was established by applying BDL. Forty-eight hours after the operation, carvedilol was administered twice a day. The blood and liver were simultaneously collected under the aseptic condition for further detection in two weeks after operation. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (Alb) in serum were measured. HE and Masson staining were used to determine hepatic fibrosis degree. Hydroxyproline assay was employed to detect liver collagen synthesis. Western Blot was used to measure the expression of TLR4, NF-κB p65 and β-arrestin2 protein. Quantitative analysis of TLR4, MyD88, TNF-α and IL-6 mRNA was performed by Realtime-PCR. Results: Compared with the SHAM group, the BDL group showed obvious liver injury, increased levels of inflammatory factors, and continued progression of liver fibrosis. The above changes in the BDL group were alleviated in the carvedilol treatment groups. The improvement effects augmented as dosages increased. In addition, compared with the BDL group, the reduction of the expressions of TLR4, MyD88 and NF-κB p65 in liver tissue and the increase of the expression of β-arrestin2 in the high-dose carvedilol group were more significant. Conclusions: Carvedilol can reduce the release of inflammatory mediators by down-regulating TLR4 expression and inhibiting its downstream signaling pathway, thus playing a potential therapeutic role in cholestatic liver fibrosis.

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