姜黄素对阿霉素肾病大鼠Notch信号通路相关蛋白的影响

目的:探讨姜黄素通过调控Notch信号通路相关蛋白表达延缓阿霉素肾病大鼠肾小球硬化进程的机制。方法:将60只SD雄性大鼠按随机数字表法分为六组,分别为空白组、模型组、对照组和姜黄素低、中、高剂量组。除空白组外,其余各组尾静脉注射阿霉素制备阿霉素肾病大鼠模型,造模成功后对照组以10 mg/kg盐酸贝那普利灌胃; 姜黄素低、中、高剂量组分别予50、100、200 mg/kg姜黄素灌胃; 空白组和模型组分别予等剂量0.9%氯化钠溶液灌胃,各组均灌胃6周。检测各组大鼠24 h尿蛋白定量、血生化指标,电镜观察大鼠肾脏病理结构改变,RT-PCR检测神经源性基因Notch同源蛋白1(Notch1)、转化生长因子β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)mRNA表达水平,免疫组化法检测Notch1、TGF-β1、MCP-1蛋白表达水平。结果:姜黄素可有效降低阿霉素肾病大鼠24 h尿蛋白定量、血肌酐和血尿素氮水平,改善肾脏病理结构,下调Notch1、TGF-β1、MCP-1 mRNA及蛋白在肾脏组织的表达,且呈剂量依赖性。结论:姜黄素可通过下调Notch信号通路相关蛋白的表达,抑制肾小球基底膜增厚和细胞外基质过度沉积,进而延缓肾小球硬化进程。

Effects of curcumin on Notch signaling pathway related protein expression in adriamycin nephropathy rats

Objective:To investigate the effect of curcumin on the progression of glomerulosclerosis in adriamycin nephropathy rats by regulating Notch signaling pathway.Methods:Sixty SD male rats were divided into six groups according to random number table method,including blank group,model group,control group and curcumin low-dose,medium-dose and high-dose groups.Except for the blank group,the other groups were given adriamycin via tail vein to make adriamycin rat nephropathy model.After successful modeling,the control group was given 10 mg/kg benazepril hydrochloride intragastric administration.Curcumin low-dose,medium-dose and high-dose groups were given 50,100 and 200 mg/kg curcumin respectively.Blank group and model group were given equal dose of 0.9% sodium chloride solution intragastric administration for 6 weeks.The 24 h urine protein quantification and blood biochemical indexes were detected.The pathological changes of kidney were observed by electron microscopy.The mRNA expression levels of Neurogenic locus notch homolog protein 1(Notch1),transforming growth factor β1(TGF-β1)and monocyte chemokine protein-1(MCP-1)were detected by RT-PCR.The protein expression levels of Notch1,TGF-β1 and MCP-1 were detected by immunohistochemistry.Results:Curcumin can effectively reduce 24 h urinary protein,serum creatinine and blood urea nitrogen levels in adriamycin nephropathy rats,improve the changes of renal pathological structure,and down-regulate the expression of Notch1,TGF-β1,MCP-1 mRNA and protein in renal tissue in a dose-dependent manner.Conclusion:Curcumin can inhibit the thickening of glomerular basement membrane and excessive deposition of extracellular matrix by down-regulating the expression of Notch signaling pathway related proteins in renal tissue,thus delaying the progression of glomerular sclerosis.