摘要
目的探讨清热益气通络方治疗糖尿病肾病(DN)大鼠蛋白尿的机制。方法 37只采用单侧肾切除腹腔注射链脲佐菌素的方法建立的糖尿病肾病大鼠模型分为3组:模型组、中药组和厄贝沙坦组,另设正常对照组。连续治疗12周后,检测24h微量白蛋白(umAlb)、24h尿蛋白量(UPro)、内生肌酐清除率(Ccr)。免疫荧光双标记足细胞表面特异性蛋白(podocalyxin)、结蛋白(desmin),荧光标记足细胞肾胚胎瘤抑制基因(wilms tumor 1,WT1)计数足细胞数及密度。光镜及电镜观察肾小球结构。结果与对照组比,模型组大鼠BW/KW、24hUPro、24humAlb、Ccr及desmin吸光度显著增高(P<0.01或P<0.05),podocalyxin吸光度及足细胞密度显著降低(P<0.01);清热益气通络方及厄贝沙坦能改善DN大鼠以上指标,与模型组比有统计学差异(P<0.01或P<0.05);清热益气通络方降低24hUPro及上调podocalyxin表达的作用优于厄贝沙坦(P<0.05)。结论清热益气通络方药能降低DN尿蛋白的排泄,其作用机制可能与拮抗podocalyxin、desmin蛋白在足细胞的异常表达、一定程度抑制DN足细胞上皮-间充质转分化有关。
Objective To investigate the mechanism of Qingre Yiqi Tongluo (QRYQTL) Fang for treating proteinuria in diabetic nephropathy (DN) rats.Methods We divided 37 rats with diabetes induced by intraperitoneal injection with STZ after unilateral nephrectomy into three model groups:diabetes model group,QRYQTL Fang treatment group and irbesartan treatment group.After 12-week treatment,24-hour urine microalbumin (umAlb),24-hour urinary protein (UPro) and creatinine clearance (Ccr) were tested; desmin,podocalyxin,and wilms tumor 1 (WT1) in glomerulus were observed by immunofluorescence double labeling.Results Compared with those in control group,the levels of 24h umAlb,24hUPro and Ccr as well as the expression of desmin were remarkably increased in model groups (P<0.01 or P<0.05),but the expression of podocalycin was significantly decreased (P<0.01).Both QRYQTL Fang and irbesartan could improve the abovementioned indicators in DN rats,which differed significantly from that in diabetes model group (P<0.01 or P<0.05).QRYQTL Fang was superior to irbesartan in decreasing 24 h UPro and upregulating the expression of podocalyxin (P<0.05).Conclusion QRYQTL Fang can reduce proteinuria in DN rats.The mechanisms may be related to inhibiting podocyte epithelial-mesenchymal transition by improving the expression of podocalyxin and decreasing the expression of desmin.
出处
《西安交通大学学报(医学版)》
CAS
CSCD
北大核心
2014年第4期537-541,共5页
Journal of Xi’an Jiaotong University(Medical Sciences)
基金
国家中医药管理局中医临床重点学科内分泌专项(No.CTX2010003-05)~~