摘要
目的分析加味芪黄饮治疗糖尿病肾病(diabetic nephropathy,DN)的机制。方法利用高脂食物联合向腹腔注入链脲佐菌素的方法建立肾病大鼠模型,按照随机原则分为4组,分别为正常组,模型组,加味芪黄饮低、高剂量组,给药组大鼠每天予加味芪黄饮400、800 mg·kg-1进行灌胃。12周后检杀,提取大鼠血液、尿液样本检测24 h尿微量白蛋白(UALB)、空腹血胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR)等指标水平,观察肾脏组织病理变化,通过电子显微镜研究细胞中线粒体的变化情况,Western Blot检测肾组织中沉默信息调节因子1(SIRT1)、发动蛋白相关蛋白-1(Drp1)等蛋白表达。结果与正常组相比,模型组大鼠24 h UALB、FIns水平及胰岛素抵抗指数均显著提高(P<0.01),说明肾小球基质开始积累,体积显著扩大及肾小管上皮组织明显受损(P<0.01);加味芪黄饮低、高剂量组大鼠以上参数相比于模型组有所降低(P<0.05),肾组织病理受损情况相比于模型组有所改观(P<0.05),且呈剂量依赖。与正常组比较,模型组大鼠肾组织中SIRT1表达升高,Drp1表达下降(P<0.05);加味芪黄饮低、高剂量组大鼠以上蛋白表达相比模型组都有所改善(P<0.05),并伴随给药剂量的提高,其改善态势更显著。结论加味芪黄饮可延缓糖尿病肾病进展,可能通过减轻线粒体损伤,改善胰岛素抵抗状态发挥作用。
Objective To analyze the mechanism of Jiawei Qihuang Yin(加味芪黄饮,JWQHY)in treating diabetic nephropathy(DN).Methods DN rat models were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin,and were randomly classified into four groups,normal group,model group,JWQHY low-dose group and high-dose group.Mice in low-dose(400 mg·kg-1)and high-dose groups(800 mg·kg-1)were treated with Jiawei Qihuang Yin by oral gavage.After 12 weeks,blood and urine samples were collected,and 24-hour urinary albumin(UALB),fasting blood glucose(FBG),fasting insulin(FIns),and insulin resistance index(HOMA-IR)were detected.The renal pathological characteristic and the changes of mitochondria in cells were observed by electron microscope.The protein expressions of silent information regulator 1(SIRT1)and dynamin-related protein 1(Drp1)were measured via Western blot.Results Compared with the normal group,remarkable increases were detected in 24-hour UALB,FIns and HOMA-IR in model group(P<0.01),suggesting an onset of glomerular mesangial matrix accumulation,volume expansion and damage to tubular epithelial tissue in renal tubular epithelial cells(P<0.01).After the interventions with JWQHY,the above parameters were decreased and the pathological damages of renal tissue were alleviated in two treatment groups in a dose dependent manner(P<0.05).An up-regulation of SIRT1 expression along with a down-regulation of Drp1 expression were observed in model group compared with normal group(P<0.05),while the expression of two proteins were improved in two treatment groups in a dose-dependent manner(P<0.05).Conclusion Application of Jiawei Qihuang Yin can delay the progression of DN,which may be related to the alleviation of mitochondrial damage and amelioration of insulin resistance.
作者
李娟
赵威
蒙向欣
李辉远
LI Juan;ZHAO Wei;MENG Xiangxin;LI Huiyuan(The Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University,Guangzhou 510130,Guangdong,China)
出处
《辽宁中医药大学学报》
CAS
2023年第4期17-21,F0003,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
广东省中医药局科研项目(20171225)。
