摘要
目的:探讨加味真武汤对慢性肾衰竭大鼠细胞凋亡信号调节激酶1(ASK1)/丝裂原活化蛋白激酶(MAPK)/核转录因子NF-κB(NF-κB)信号通路及肾纤维化的影响。方法:60只Wistar雄性大鼠分为对照组、模型组、阳性药组(卡托普利,5mg/kg)、加味真武汤低剂量组(0.245g/kg)、加味真武汤高剂量组(0.98g/kg),每组20只。除正常组外,其余各组大鼠建立慢性肾衰竭模型,分组给予相应药物处理后,全自动生化分析仪检测血清中尿素氮(BUN)、血肌酐(Scr)水平;采用ELISA法检测血清转化生长因子β1(TGF-β1)、单核细胞趋化蛋白1(MCP-1)水平;苏木精-伊红染色(HE)染色观察大鼠肾组织病理生理变化;Western blot法进行肾组织ASK1/MAPK/NF-κB信号通路蛋白检测。结果:与假手术组相比,模型组大鼠生活质量较差,肾组织出现肾小球硬化、其周围组织纤维化、肾间质大量炎性细胞浸润等病变,血清中BUN、SCr、TGF-β1、MCP-1表达水平及肾组织中ASK1、p-MAPK、p-NF-κB蛋白表达水平显著上升(P<0.05);给药治疗后,低剂量组、阳性药组、高剂量组较模型组大鼠生活质量及肾组织病理症状均有所改善,且高剂量组效果最明显,血清中BUN、SCr、TGF-β1、MCP-1表达水平及肾组织中ASK1、p-MAPK、p-NF-κB蛋白表达水平依次下降(P<0.05)。结论:加味真武汤可抑制ASK1活性,降低MAPK、NF-κB蛋白磷酸化水平,减轻肾组织炎症损伤,减缓肾组织纤维化进程,本研究可为加味真武汤的临床应用提供理论参考。
Objective:The objective of this study is to investigate the effects of Jiawei Zhenwu Tang on the apoptosis signaling-regulated kinase 1(ASK1)/mitogen-activated protein kinase(MAPK)/nuclear transcription factor NF-κB(NF-κB)signaling pathway and renal fibrosis in rats with chronic renal failure.Methods:Sixty male Wistar rats were randomly assigned to five groups,including the control group,model group,positive drug group(captopril,5mg/kg),plus-mei-zenwu-tang lowdose group(0.245g/kg),and plus-mei-zenwu-tang high-dose group(0.98g/kg),with 20 rats in each group.Except for the control group,chronic renal failure was induced in rats in all other groups.The rats were then treated with corresponding drugs.Pathophysiological changes of rat kidney tissues were observed,and Western blot assays were performed to detect ASK1/MAPK/NF-κB signaling pathway proteins in kidney tissues.Results:Compared with the control group,rats in the model group exhibited poor quality of life,renal tissues showed lesions such as glomerulosclerosis,fibrosis of surrounding tissues,and massive inflammatory cell infiltration in the renal interstitium.The expression levels of BUN,SCr,TGF-β1,and MCP-1 in serum,as well as ASK1,p-MAPK,and p-NF-κB protein expression levels in renal tissues were significantly increased(P<0.05).After treatment,the quality of life and renal histopathological symptoms of rats in the low-dose,positive drug,and high-dose groups improved compared with those in the model group.The effect was most significant in the high-dose group,with the expression levels of BUN,SCr,TGF-β1,and MCP-1 in serum and the expression levels of ASK1,p-MAPK,and p-NF-κB proteins in renal tissues decreasing sequentially(P<0.05).Conclusion:Jiawei Zhenwu Tang can inhibit ASK1 activity,reduce MAPK and NF-κB protein phosphorylation levels,reduce inflammatory damage in renal tissues,and slow down the process of renal tissue fibrosis.The findings of this study provide a theoretical reference for the clinical application of Jiawei Zhenwu Tang.
作者
王世卫
马民凯
韩佳
耿兴华
WANG Shiwei;MA minkai;HAN Jia(Department of Nephrology,Baoding fourth central hospital,Baoding Hebei 072350,China;Department of integrated traditional Chinese and Western medicine,Baoding fourth central hospital,Baoding Hebei 072350,China)
出处
《四川中医》
2023年第4期38-42,共5页
Journal of Sichuan of Traditional Chinese Medicine
基金
保定市科技计划项目(项目编号:1951ZF039)
