莲心碱对链脲佐菌素所致糖尿病肾病大鼠影响的研究  

A study on effects of liensinine on streptozotocin-induced diabetic nephropathy rats

作　　者：王红萍 宋蝶 何微 马松涛[1] WANG Hongping

机构地区：[1]成都医学院药学院,四川成都610500

出　　处：《中医临床研究》2024年第32期25-29,共5页Clinical Journal Of Chinese Medicine

基　　金：四川省科技厅项目(2015JY0131)。

摘　　要：目的:研究莲心碱对链脲佐菌素诱导的大鼠糖尿病肾病模型的影响。方法:造模组大鼠经尾静脉注射给予链脲佐菌素进行造模,对照组则给予等体积的柠檬酸盐缓冲液。造模成功后,采用随机抽样法将糖尿病大鼠分为模型组(等体积生理盐水)、卡托普利组(卡托普利10 mg/kg),莲心碱低剂量组(莲心碱2 mg/kg)、莲心碱中剂量组(莲心碱4 mg/kg)、莲心碱高剂量组(莲心碱8 mg/kg),每组10只。另选10只健康大鼠设为空白组。给予链脲佐菌素诱导的糖尿病肾病大鼠连续12周莲心碱治疗,测定24小时尿微量白蛋白、尿蛋白含量和肾脏病理学的变化,同时采用逆转录聚合酶链反应(Reverse Transcription-Polymerase Chain Reaction,RT-PCR)检测大鼠肾皮质中肾病蛋白、足突蛋白质和乙酰肝素酶(Heparanase,HPSE)的mRNA表达水平,采用蛋白免疫印迹(Western Blot,WB)测定转化生长因子(Transforming Growth Factor,TGF)-β1和IV型胶原的表达。探讨莲心碱的作用机制。结果:莲心碱治疗后,大鼠尿白蛋白、微量白蛋白排泄显著减少,与模型组有显著差异,并表现出一定的浓度依赖特性。治疗后,与模型组相比,各剂量组可见大鼠肾小球基底膜厚度、肾小球最大直径和胶原堆积均明显降低。透射电镜观察结果显示空白组足突结构正常,足细胞无凋亡、脱落现象;模型组足突增宽,足细胞数量减少。与模型组比较,莲心碱高剂量组、莲心碱中剂量组、莲心碱低剂量组足突宽度均显著降低(P<0.01),足细胞数量增加。定量聚合酶链反应(Quantitative Polymerase Chain Reaction,qPCR)结果显示,与模型组比较,大鼠肾组织肾病蛋白、足突蛋白质相对表达量增加,HPSE相对表达量减少,均以莲心碱高剂量组变化最为明显,差异具有统计学意义(P<0.01)。结论:莲心碱可能通过上调肾病蛋白、足突蛋白质的表达,以及下调HPSE水平,恢复肾小球滤过屏障,同时通过下调TGF-β1Objective:To study the effect of liensinine on streptozotocin-induced diabetic nephropathy model rats.Methods:The Orats in the model group were injected with streptozotocin via tail vein to establish the model,while the control group was given an equal volume of citrate buffer solution.After successful modeling,the diabetic rats were randomly divided into the model group(equal volume of saline),the captopril group(captopril 10 mg/kg),the low-dose liensinine group(liensinine 2 mg/kg),the medium-dose liensinine group(liensinine 4 mg/kg),and the high-dose liensinine group(liensinine 8 mg/kg),with 10 rats in each group.Another 10 healthy rats were selected as the blank group.Streptozotocin-induced diabetic nephropathy rats were treated with liensinine for 12 consecutive weeks.Changes in 24-hour urinary microalbumin,urinary protein content,and renal pathology were determined.The mRNA expression levels of nephrin,podocin and HPSE in the rats’renal cortex were detected by RT-PCR.The expressions of TGF-β1 and collagen type IV were determined by WB.This study aimed to investigate the mechanism of action of liensinine.Results:The urinary albumin and microalbumin excretion in rats were significantly reduced after liensinine treatment,which was significantly different from that in the model group and showed certain concentration-dependent characteristics.After treatment,glomerular basement membrane thickness,glomerular maximum diameter and collagen accumulation in rats in the liensinine groups were significantly reduced compared with the model group.The results of transmission electron microscopy showed that the foot process structure in the blank group was normal,and there was no apoptosis or shedding of podocytes in the model group.Compared with the model group,the width of the foot process was significantly reduced in the liensinine groups(P<0.01),and the number of podocytes was increased.The qPCR results showed that compared with the model group,the relative expressions of nephrin and podocin were increased and the re

关 键 词：莲心碱 糖尿病肾病 肾病蛋白 足突蛋白质 转化生长因子-Β1 

分 类 号：R284.5[医药卫生—中药学]