Effect of Propylene Glycol Alginate Sodium Sulfate Nanoparticles on Myocardial Injury in Diabetic Rats via Silent Information Regulator 1/Hypoxia-Inducible Factor-1 Alpha Pathway

2021 ◽  
Vol 21 (2) ◽  
pp. 1351-1356
Author(s):  
Sheng Qiu ◽  
Lei Cai ◽  
Wenjing Zhao ◽  
Xiaohong Pang

The main purpose of this paper is to study the effect of propylene glycol alginate sodium sulfite nanoparticles on myocardial injury in diabetic rats through Sirt1/HIF-1 α signal pathway. The effects of different doses of propylene glycol alginate sodium sulfite nanoparticles on the content of malondialdehyde, creatine kinase, nitric oxide, the activity of superoxide dismutase, lactate dehydrogenase and nitric oxide synthetase in the myocardial tissue of diabetic rats observed. The function indexes of HIF-1 α mitochondria and measured the expression of Sirt1/HIF-1 α pathway. The results show that compare with the diabetic model group, the blood glucose level of the rats in the propylene glycol alginate sodium sulfite nanoparticles treatment group was slightly low. The serum LDH, CK and MDA contents were significantly low, and the activity of SOD in the myocardium in the propylene glycol alginate sodium sulfite nanoparticles treatment group was significantly higher than that in the diabetic model group in the treatment group. The activity of NOS and the content of MDA and no were lower than that in the diabetic rats, the expression of Sirt1 and HIF-1α in myocardial tissue was increased. It suggested that propylene glycol alginate sodium sulfite nanoparticles alleviate myocardial damage in diabetic rats by regulating Sirt1/HIF-1α signal pathway, improving mitochondrial function and inhibiting oxidative stress.

2021 ◽  
Vol 11 (9) ◽  
pp. 1799-1804
Author(s):  
Hongbing Xiao ◽  
Wei Hu ◽  
Jun Gu ◽  
Dandan Li

Ursolic acid can clear free radicals and prevent the formation of non-enzymatic glycosylation products. Our study assessed the inhibitory effect of UA on the myocardial tissue of mice. 36 healthy mice were equally and randomly divided into 3 groups by double blind method, sham operation group, model group and ursolic acid group. Myocardial injury model was established and treated with ursolic acid followed by analysis of cell morphological structure and apoptosis; levels of serum CK, AST, LDH activity and IL-6, IL-1β and TNF-α levels, as well as expression of p-AKT, AKT and PI3K in myocardial tissue. The morphological structure and apoptosis of ursolic acid group were improved compared to model group (P < 0.05). CK, AST, LDH, p-AKT and PI3K level in serum of ursolic acid group was significantly decreased (P <0.05) along with significantly downregulate IL-6, IL-1β, TNF-α (P <0.05). Ursolic acid ameliorates myocardial injury in mice possibly through inhibition of AKT/P13K signaling pathway to reduce inflammatory cascade in the body.


2020 ◽  
Vol 19 (3) ◽  
pp. 565-569
Author(s):  
Zhihong Zhao ◽  
Xuejing Wang ◽  
Xiumin Li ◽  
Hongshuang Li ◽  
Bin Xu

Purpose: To investigate the protective effect of astragalus injection against myocardial injury in septic young rats, and the underlying mechanism of action. Methods: Seventy-two healthy Sprague Dawley (SD) rats were randomly selected and used to establish a young rat model of sepsis. The young rats were randomly divided into 3 groups: sham, model and astragalus injection groups. Each group had 24 young rats. Serum cardiac troponin I (cTnI), IL-10, IL-6, JAK2 and STAT3 were measured after op. Results: Compared with sham group, serum cTnI level in the model group was significantly higher, while serum cTnI level of the drug group was significantly lower than that of the model group (p < 0.05). Compared with model group, the level of IL-10 in the myocardial tissue of the drug group was significantly elevated, while IL-6 level was lower (p < 0.05). Relative to sham rats, myocardial JAK2 and STAT3 protein levels in model rats were high. However, myocardial JAK2 and STAT3 proteins in the drug-treated rats were significantly downregulated, relative to model rats (p < 0.05). Conclusion: Astragalus injection upregulates IL-10 and IL-6 in rats by inhibiting the activation of JAK/STAT signal pathway, and via maintenance of pro-inflammation/anti-inflammation balance. Thus, astragalus exerts protective effect against myocardial injury in sepsis, and can potentially be developed for use as such in clinical practice. Keywords: Astragalus injection, JAK/STAT signal pathway, Pro-inflammatory/anti-inflammatory imbalance, Sepsis, Myocardial injury


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Fan Yang ◽  
Yachun Li ◽  
Shuai Guo ◽  
Yongmei Pan ◽  
Cuihuan Yan ◽  
...  

As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Yao Duan ◽  
Yan Liang ◽  
Wen-Ping Gong ◽  
Yong Xue ◽  
Jie Mi ◽  
...  

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.


2021 ◽  
Author(s):  
Rajiv Kumar ◽  
Poorva Bhargava ◽  
Kapiil Suchal ◽  
Jagriti Bhatia ◽  
Dharamvir Singh Arya

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianjun Wu ◽  
Shoupin Xie ◽  
Hailong Li ◽  
Yanxia Zhang ◽  
Jia Yue ◽  
...  

Abstract Background Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice Methods The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured Results There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) Conclusions This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.


2020 ◽  
Author(s):  
Qi Zhang ◽  
Zheng Shu-guang ◽  
Wang Bao-juan ◽  
Wang Lin ◽  
Li Tian-yang

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.


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