人参皂苷 Rg1 对脓毒症所致心肌损伤大鼠 NF-κB 磷酸化水平及炎症相关 通路的影响.

Objective: To explore effect of ginsenoside Rg1 on nuclear factor-κB(NF-κB) phosphorylation and inflammationrelated pathways in rats with myocardial injury caused by sepsis. Methods: Rat sepsis myocardial injury model was established by cecal ligation and puncture(CLP). Sixty rats were randomly divided into sham operation(sham) group, CLP group, ginsenoside Rg1 low-dose(CLP+Rg1L ) group, ginsenoside Rg1 medium-dose(CLP+Rg1M) group, ginsenoside Rg1 high-dose(CLP+Rg1H ) group and risatovir(CLP+TAK-242) group, with 10 rats in each group. Sepsis cardiomyocyte model in vitro was constracted by LPS. H9C2 cells were divided into control group, LPS group, LPS+Rg1L group, LPS+Rg1M group, LPS+Rg1H group, LPS+TAK-242 group. Right common carotid artery cannulation method was used to detect mean arterial blood pressure(MABP), heart rate×left ventricular development pressure(LVDP×HR), and maximal increase/decrease rate of left ventricular pressure(±dp/dtmax) in each group. Myocardial histopathological changes was observed by HE staining. Apoptosis of myocardial tissues and H9C2 cells were detected by Annexin VFITC/PI double staining. Creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), cardiac troponin Ⅰ(cTnⅠ), tumor necrosis factor-α(TNF-α), IL-6, IL-1β levels in rat serum and H9C2 cells were detected by ELISA. Proliferation ability of H9C2 cells was detected by CCK-8 and EdU staining. RT-qPCR detected myocardial tissues Toll-like receptor 4(TLR4), NF- κB p65, p38 mitogen activated protein kinase(p38MAPK) mRNA expressions. Western blot detected protein expressions of TLR4, NF-κB p65, p-NF-κB p65, p38MAPK, p-p38MAPK and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3) in myocardial tissues. Results: Ginsenoside Rg1 could increase levels of MABP, LVDP×HR and ±dp/dtmax, decrease activities of CK, LDH and AST, and decrease levels of cTnⅠ, TNF-α, IL-6, IL-1β, TLR4, NF-κB p65, p38MAPK mRNA and TLR4, NF-κB p65, p-p38MAPK/p38MAPK, NLRP3 proteins(P<0.05), promote cardiomyocyte proliferation, inhibit apoptosis and inflammation, and improve myocardial injury. Conclusion: Ginsenoside Rg1 can inhibit myocardial tissue cell apoptosis and inflammation, improve cardiac function, and reduce myocardial injury caused by sepsis, whose mechanism may be related to TLR4/NF- κB and p38MAPK signaling pathways. [ABSTRACT FROM AUTHOR]