肾炎防衰液通过FGF21/SIRT1信号通路防治糖尿病肾病的机制研究  

Mechanism of nephritis aiti-failure decoction in the prevention and treatment of diabetic nephropathy via FGF21/SIRT1 signal pathway

作　　者：孙娜 陈振杰 吕杰[1] 和莹 梁瑛楠 王健[1] 周静威[1] SUN Na;CHEN Zhenjie;LYU Jie;HE Ying;LIANG Yingnan;WANG Jian;ZHOU Jingwei(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《现代中西医结合杂志》2023年第14期1911-1918,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金项目(81874401)。

摘　　要：目的观察肾炎防衰液对糖尿病肾病(DN)小鼠的干预作用,并基于成纤维细胞生长因子21(FGF21)/沉默信息调节蛋白1(SIRT1)信号通路探讨其防治DN的潜在分子机制。方法将40只雄性C57BL/6小鼠随机分为正常组、模型组、肾炎防衰液组及厄贝沙坦组,每组10只。除正常组外,其余组小鼠采用高脂饲料喂养联合小剂量多次腹腔注射链脲佐菌素(STZ)方法构建DN模型。造模成功后,肾炎防衰液组给予肾炎防衰液20.93 g/(kg·d)灌胃,厄贝沙坦组给予厄贝沙坦22.75 mg/(kg·d)灌胃,正常组和模型组给予等量的生理盐水灌胃,均每日1次,连续12周。灌胃期间观察各组小鼠的体重和血糖水平;灌胃结束后,检测各组小鼠肾功能指标[尿白蛋白肌酐比(UACR)、血尿素氮(BUN)、血肌酐(SCr)]、肾重/体重比、脂代谢指标[血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平]、血清FGF21水平,HE、PAS、Masson染色观察肾脏病理形态,免疫组化染色观察肾脏组织中SIRT1蛋白表达情况,免疫荧光染色观察肾脏组织中LC3、p62蛋白表达情况。结果灌胃前,各造模组小鼠体重、血糖明显高于正常组(P均<0.05)。灌胃结束后,模型组小鼠UACR、肾重/体重比及血清TG、TC、LDL-C、FGF21水平均明显高于正常组(P均<0.05);HE、PAS、Masson染色见肾小球体积增大,肾小管上皮细胞广泛空泡变性坏死,肾小球硬化、纤维化改变明显;肾脏组织中SIRT1、LC3蛋白表达少于模型组(P均<0.05),p62蛋白表达多于模型组(P<0.05)。与模型组比较,肾炎防衰液组及厄贝沙坦组小鼠UACR和肾炎防衰液组血清TG、TC、LDL、FGF21水平均明显降低(P均<0.05),HE、PAS、Masson染色见小鼠肾脏病理损伤改善,肾脏组织中SIRT1、LC3蛋白表达增多而p62蛋白表达减少(P均<0.05)。结论肾炎防衰液可明显减轻DN小鼠肾组织损伤,保护肾脏,机制可能与调控FGF21/SIRT1通路、增强自噬有关。Objective It is to observe the intervention effect of nephritis aiti-failure decoction on diabetic nephropathy(DN)mice,and to explore the potential molecular mechanism of this decoction in the prevention and treatment of DN based on fibroblast growth factor 21(FGF21)/silent information regulatory protein 1(SIRT1)signaling pathway.Methods Forty male C57BL/6 mice were randomly divided into normal group,model group,nephritis aiti-failure decoction group and irbesartan group,with 10 mice in each group.The mice in every group except for the normal group were fed with high-fat diet combined with streptozotocin(STZ)by small-dose multiple intraperitoneal injections to establish DN models.After successful modeling,the nephritis aiti-failure decoction group was given nephritis aiti-failure decoction 20.93 g/(kg·d)by gavage,the irbesartan group was given irbesartan 22.75 mg/(kg·d)by gavage,and the normal group and model group were given an equal amount of normal saline by gavage,all once daily,continuously treated for 12 weeks.The body weight and blood glucose levels of mice in each group during the treatment were observed;after treatment,the renal function indexes[urinary albumin-creatinine ratio(UACR),blood urea nitrogen(BUN),and serum creatinine(SCr)],renal weight/body weight ratios,lipid metabolism indexes[serum total cholesterol(TC),triacylglycerol(TG),and low-density lipoprotein cholesterol(LDL-C)],serum FGF21 of mice in each group were determined,the renal pathological morphology was observed by HE,PAS,and Masson staining,the expression of SIRT1 protein in renal tissue was observed by immunohistochemical staining,the expression of LC3 and p62 protein in renal tissue was observed by immunofluorescence staining.Results Before gavage,the body weight and blood glucose of mice in each modeling group were significantly higher than those of the normal group(all P<0.05).At the end of gavage,the UACR,kidney weight/body weight ratio and the levels of serum TG,TC,LDL-C,FGF21 of mice in the model group were significantly highe

关 键 词：糖尿病肾病 肾炎防衰液 自噬 成纤维细胞生长因子21 沉默信息调节蛋白1 

分 类 号：R-332[医药卫生]