丹蛭降糖胶囊改善db/db小鼠肾组织损伤的作用机制  

Mechanism of Danzhi Jiangtang capsule in improving kidney tissue injury in db/db mice

作　　者：阮诺冰 方朝晖[2,3] 李金菊 许奇 李瑜璠 胡可心 RUAN Nou-bing;FANG Zhao-hui;LI Jin-ju;XU Qi;LI Yu-fan;HU Ke-xin(The First Clinical College,Anhui University of Chinese Medicine,Hefei 230031,Anhui Province,China;Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,Anhui Province,China;Xin'an Institute of Medicine and Modernization of Chinese Medicine,National Science Center's Institute of Comprehensive Health,Hefei 230000,Anhui Province,China;Graduate School,Anhui University of Chinese Medicine,Hefei 230031,Anhui Province,China)

机构地区：[1]安徽中医药大学第一临床医学院,安徽合肥230031 [2]安徽中医药大学第一附属医院内分泌科,安徽合肥230031 [3]合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所,安徽合肥230000 [4]安徽中医药大学研究生院,安徽合肥230031

出　　处：《中国临床药理学杂志》2025年第4期517-521,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(82174153,81573944,81774286);中央财政转移支付地方基金资助项目(2023-24);新安医学与中医药现代化“揭榜挂帅”基金资助项目(2023CXMMTCM003)。

摘　　要：目的探讨丹蛭降糖胶囊对糖尿病肾病(DKD)db/db小鼠肾保护作用及对自噬-溶酶体途径的影响。方法将db/db小鼠随机分为模型组(0.2 mL·d^(-1)0.9%NaCl)、阳性对照组(45 mg·kg^(-1)·d^(-1)厄贝沙坦)和高、中、低剂量实验组(1800、900、450 mg·kg^(-1)·d^(-1)丹蛭降糖胶囊),另以db/m小鼠作为空白组(0.2 mL·d^(-1)0.9%NaCl),连续灌胃给药8周。用蛋白质印迹法检测肾组织选择性自噬接头蛋白p62(P62)、微管相关蛋白轻链3(LC3)、转录因子EB(TFEB)、溶酶体关联膜蛋白1(LAMP-1)、组织蛋白酶Cathepsin D(CTSD)的相对表达水平。结果空白组、模型组、阳性对照组和高、中、低剂量实验组P62蛋白相对表达水平分别为1.00±0.04、7.66±0.27、3.52±0.11、2.21±0.09、2.86±0.10和4.05±0.16,LC3Ⅱ/Ⅰ分别为1.00±0.02、0.17±0.01、0.71±0.08、0.86±0.05、0.80±0.04和0.73±0.06,TFEB蛋白相对表达水平分别为1.00±0.01、0.17±0.01、0.30±0.01、0.63±0.01、0.45±0.01和0.42±0.01,LAMP-1蛋白相对表达水平分别为1.00±0.01、0.28±0.02、0.42±0.01、0.77±0.00、0.55±0.03和0.40±0.02,CTSD蛋白相对表达水平分别为1.00±0.04、0.27±0.03、0.47±0.04、0.73±0.02、0.63±0.01和0.52±0.02。高、中、低剂量实验组的上述指标与模型组比较,在统计学上差异有统计学意义(均P<0.01)。结论丹蛭降糖胶囊可改善db/db小鼠肾损害,可能与修复自噬-溶酶体途径,激活自噬,加速清除异常蛋白质和降解细胞器有关。Objective To investigate the protective effect of Danzhi Jiangtang capsule on kidney of db/db mice with diabetic kidney disease(DKD)and its effects on the autophagy-lysosomal pathway.Methods The db/db mice were randomly divided into model group(0.2 mL·d^(-1)0.9%NaCl),positive control group(45 mg·kg^(-1)·d^(-1)irbesartan)and experimental-H,-M,-L groups(1800,900 and 450 mg·kg^(-1)·d^(-1)Danzhi Jiangtang capsule),and another db/m mice were taken as blank group(0.2 mL·d^(-1)0.9%NaCl),which were continuously infused for 8 weeks.The expression levels of sequestosome1(P62),microtubule-associated protein light chain 3(LC3),transcription factor EB(TFEB),lysosomal associated membrane protein 1(LAMP-1)and cathepsin D(CTSD)were detected in renal tissues by Western blot.Results The relative expression levels of P62 protein in blank group,model group,positive control group and experimental-H,-M,-L groups were 1.00±0.04,7.66±0.27,3.52±0.11,2.21±0.09,2.86±0.10 and 4.05±0.16;the LC3Ⅱ/Ⅰlevels were 1.00±0.02,0.17±0.01,0.71±0.08,0.86±0.05,0.80±0.04 and 0.73±0.06;the TFEB protein levels were 1.00±0.01,0.17±0.01,0.30±0.01,0.63±0.01,0.45±0.01 and 0.42±0.01;the LAMP-1 protein levels were1.00±0.01,0.28±0.02,0.42±0.01,0.77±0.00,0.55±0.03 and 0.40±0.02;the CTSD protein levels were1.00±0.04,0.27±0.03,0.47±0.04,0.73±0.02,0.63±0.01 and 0.52±0.02.The differences between the above indexes in the experimental-H,-M,-L groups and the model group were statistically significant(all P<0.01).Conclusion Danzhi Jiangtang capsule can improved renal damage in db/db mice,which may be related to the repair of autophagy-lysosome pathway,accelerate clearance of abnormal proteins and degradation of organelles.

关 键 词：丹蛭降糖胶囊 糖尿病肾病 自噬-溶酶体途径 肾损伤 

分 类 号：R28[医药卫生—中药学]