基于自噬通路探讨化瘀通络中药对db/db小鼠肾脏的保护作用及机制  

Exploring the Protective Effect and Mechanism of Huayu-tomgluo Recipe on Kidney of db/db Mice Based on Autophagy Pathway

作　　者：王开爽 马赟[2] 杨帆 张学琴 张天伟 吴媛 刘照 刘冬梅[2] 陈志强 WANG Kaishuang;MA Yun;YANG Fan(The First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang(050013))

机构地区：[1]河北中医药大学第一附属医院,石家庄050013 [2]河北省中医院,石家庄050013 [3]河北中医药大学,石家庄050091

出　　处：《中国中西医结合肾病杂志》2025年第1期10-16,I0001,共8页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金资助项目(No.82274504);河北省省级科技计划资助项目(No.20377711D);河北省中医药管理局科研计划项目(No.2023119);河北省中医药管理局科研计划项目(No.2020039);河北中医药大学研究生创新资助立项项目(No.XCXZZBS2023019)。

摘　　要：目的:探讨化瘀通络中药对db/db小鼠肾脏保护作用,并基于自噬通路探究其机制。方法:选取SPF级8周龄db/db小鼠24只,随机分为模型组(M组)、化瘀通络组(Z组),恩格列净组(E组)每组8只;以同群体杂合型db/m小鼠8只为正常组(N组)。适应性喂养1周后,Z组、E组分别予化瘀通络中药颗粒、恩格列净,N组、M组小鼠予纯水,每日1次。干预12周。检测UACR、BUN、Scr、GA;留取肾组织标本,观察肾脏组织病理改变,WB及IHC法检测Nephrin、CD2AP、LC3B-Ⅱ、p62、Bcl-2、Bax的表达。结果:与正常组相比,模型组UACR、BUN、GA显著升高,肾小球系膜细胞及系膜基质增生,基底膜轻度增厚,Nephrin、CD2AP、LC3B-Ⅱ、Bcl-2表达减少,p62、Bax表达增多(P<0.01)。与模型组相比,Z组、E组UACR下降;肾脏病理改变减轻;肾脏足细胞标志蛋白Nephrin及CD2AP的表达增加,同时LC3B-Ⅱ、Bcl-2的表达升高,p62、Bax的表达降低(P<0.01),两治疗组间以上指标差异无统计学意义(P>0.05)。结论:化瘀通络中药可不依赖于降糖作用而延缓糖尿病肾病进展,效果与应用恩格列净相似,其机制可能与激活足细胞自噬,抑制足细胞凋亡有关。Objective:To investigate the renal protective effect of Huayu-Tongluo Recipe on db/db mice,and to explore its mechanism based on autophagy pathway.Methods:Twenty-four 8-week-old SPF db/db mice were randomly divided into model group(M group),Huayu-Tongluo group(Z group)and empagliflozin group(E group),with 8 mice in each group.Eight heterozygous db/m mice of the same population were used as the normal group(group N),adaptive feeding for 1 week.Mice in Z and E groups were treated with Huayu-Tongluo Recipe granules and empagliflozin respectively,while mice in N and M groups were treated with pure water,once a day for 12 weeks.UACR of urine samples before and after treatment and BUN,Scr,GA of serum samples after treatment were detected.The expressions of Nephrin,CD2AP,LC3B-Ⅱ,p62,Bcl-2 and Bax were detected by Western Blot and immunohistochemistry.Results:Compared with the normal group,the UACR,BUN and GA of the model group were significantly increased;the glomerular mesangial cells and mesangial matrix proliferated,the basement membrane was slightly thickened,the expressions of Nephrin,CD2AP,LC3B-Ⅱ,and Bcl-2 were decreased,and the expressions of p62 and Bax were increased(P<0.01).Compared with the model group,UACR of both Z and E groups decreased;the renal pathological changes were milder than those of the model group.The expressions of Nephrin,CD2AP,LC3B-Ⅱand Bcl-2 were increased,and the expressions of p62 and Bax were decreased(P<0.01).There was no significant difference of the above results between the two treatment groups(P>0.05).Conclusion:Huayu-Tongluo Recipe can delay the progression of diabetic nephropathy independent of its hypoglycemic effect,which effect is similar to that of empagliflozin.The mechanism may be related to the activation of podocyte autophagy and the inhibition of podocyte apoptosis.

关 键 词：足细胞 自噬 凋亡 糖尿病肾病 化瘀通络 中药 

分 类 号：R285.5[医药卫生—中药学]