消瘀泄浊饮对糖尿病肾病小鼠肾脏足细胞凋亡及HIF1α表达的调控作用  

Effect of Xiaoyu Xiezhuo Drink on Podocyte Apoptosis and Expression of HIF 1αin Diabetic Kidney Disease Mice

作　　者：傅兰君 叶晴晴 范桢亮 范军芬[1] 陈红波[1] 马红珍[1] 何强 FU Lanjun;YE Qingqing;FAN Zhenliang(The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China)

机构地区：[1]浙江中医药大学附属第一医院,杭州310006

出　　处：《浙江中医药大学学报》2024年第3期247-254,共8页Journal of Zhejiang Chinese Medical University

基　　金：浙江省医药卫生科技计划项目(2022KY916、2021KY833);浙江省中医药科学研究基金项目(2021ZB110)。

摘　　要：[目的]探讨消瘀泄浊饮对糖尿病肾病(diabetic kidney disease,DKD)小鼠肾脏足细胞凋亡的保护作用及对低氧诱导因子1α(hypoxia inducible factor 1 alpha,HIF1α)的影响。[方法]选用6只db/m小鼠为阴性对照组,18只db/db小鼠随机分为DKD模型组、低剂量消瘀泄浊饮组、高剂量消瘀泄浊饮组,每组6只。灌胃12周后,检测尿液中尿蛋白、β_(2)-微球蛋白(β_(2)-microglobulin,β_(2)-MG)、尿白蛋白/肌酐(albumin/creatinine ratio,Acr)、尿β_(2)-微球蛋白/肌酐(β_(2)-microglobulin/creatinine ratio,β_(2)-MG/Ucr)及血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、白蛋白(albumin,Alb)、尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,Scr)的水平。分离肾组织,光镜及电镜下观察肾组织病理变化;组织匀浆后用实时聚合酶链式反应(Real-time polymerase chain reaction,RT-PCR)法检测HIF1α、nephrin mRNA水平。[结果]与阴性对照组比较,DKD模型组小鼠的尿蛋白、尿β_(2)-MG、Acr、β_(2)-MG/Ucr,血清TG、TC、BUN、Scr水平升高(P<0.01),血清Alb下降(P<0.01);肾小球体积增大,毛细血管袢呈分叶状,系膜细胞及基质增生,间质炎症及纤维化程度加重,足突融合增加,基底膜增厚,足细胞凋亡增加;肾组织HIF1αmRNA表达升高(P<0.01),nephrin mRNA表达下降(P<0.01)。与DKD模型组比较,高、低剂量消瘀泄浊饮组的尿蛋白、尿β_(2)-MG、Acr、β_(2)-MG/Ucr,血清TG、TC、BUN、Scr水平下降(P<0.01),血清Alb水平升高(P<0.01);肾小球、肾间质、足突病变明显改善,足细胞凋亡减少;肾组织HIF1αmRNA表达下降(P<0.01),nephrin mRNA表达升高(P<0.01)。高、低剂量消瘀泄浊饮组间尿蛋白、β_(2)-MG、Acr、β_(2)-MG/Ucr,血清TG、TC、BUN、Scr、Alb水平和肾组织HIF1α、nephrin mRNA表达差异无统计学意义(P>0.05)。[结论]消瘀泄浊饮能改善DKD小鼠尿蛋白、肾功能及肾脏结构病变、足细胞凋亡等指标,其可能通过调节HIF1α表达发挥[Objective]To observe the effect of Xiaoyu Xiezhuo Drink on podocyte apoptosis and hypoxia inducible factor 1 alpha(HIF 1α)expression in db/db diabetic kidney disease(DKD)model mice.[Methods]Six db/m mice were chosen as negative control group,eighteen db/db mice were chosen and divided into DKD model group,low dosage Xiaoyu Xiezhuo Drink group,high dosage Xiaoyu Xiezhuo Drink group,with six mice in each group.After gastric irrigation for twelve weeks,the urine was collected to test the levels of protein,β_(2)-microglobulin(β_(2)-MG),albumin/creatinine ratio(Acr),β_(2)-microglobulin/creatinine ratio(β_(2)-MG/Ucr);blood was collected to test the level of triglyceride(TG),total cholesterol(TC),albumin(Alb),blood urea nitrogen(BUN),serum creatinine(Scr);the kidney tissue was collected to observe the pathological change by light and electron microscope,and to test HIF 1α,nephrin mRNA by Real-time polymerase chain reaction(RT-PCR).[Results]Compared with negative control group,the levels of urine protein,β_(2)-MG,Acr,β_(2)-MG/Ucr,serum TG,TC,BUN,Scr were increased(P<0.01),serum Alb was decreased(P<0.01);glomerular volume increased,capillary loops lobed,mesangial cells and matrix hyperplasia,interstitial inflammation and fibrosis increased,foot process fusion increased,basement membrane thickened;podocyte apoptosis was increased;expression of HIF 1αmRNA was elevated(P<0.01),and nephrin mRNA was descended in kidney tissue of DKD model group(P<0.01).Compared with DKD model group,the level of urine protein,β_(2)-MG,Acr,β_(2)-MG/Ucr,serum TG,TC,BUN,Scr were decreased(P<0.01),serum Alb was incresed(P<0.01);the pathological changes of the kidney was improved;the apoptosis of podocyte was reduced;the expression of HIF 1αmRNA was decreased(P<0.01),and nephrin mRNA was incresed(P<0.01)in the kidney tissue of varied dosage Xiaoyu Xiezhuo Drink groups.There was no statistical significance in the level of urine protein,β_(2)-MG,Acr,β_(2)-MG/Ucr,serum TG,TC,BUN,Scr,Alb,podocyte apoptosis,and HIF 1α,nephrin mRNA in the

关 键 词：糖尿病肾病 消瘀泄浊饮 肾功能不全 足细胞凋亡 氧化应激 低氧诱导因子1ɑ 

分 类 号：R331[医药卫生—人体生理学]