玉蚕颗粒缓解db/db小鼠肾纤维化的作用机制  

Mechanism of Yucan Granules on alleviating renal fibrosis in db/db mice

作　　者：盛广宇 张亚亨 宋婷 俞菁鉴 阮伟 杨涛[1] 杨雪军[1,2] SHENG Guangyu;ZHANG Yaheng;SONG Ting;YU Jingjian;RUAN Wei;YANG Tao;YANG Xuejun(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201200,China;Department of Nephrology,Anhui Integrated Traditional Chinese and Western Medicine Hospital(Third Affiliated Hospital of Anhui University of Traditional Chinese Medicine),Hefei,Anhui 230000,China)

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海201200 [2]安徽省中西医结合医院(安徽中医药大学第三附属医院)肾内科,安徽合肥230000

出　　处：《上海中医药杂志》2025年第5期67-75,共9页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市科委“科技创新行动计划”医学创新研究专项(22Y31920200);安徽省高等学校科学研究项目(2023AH040100);上海市浦东新区卫健委卫生行业专项(PW2021E-02)。

摘　　要：目的通过db/db小鼠探讨玉蚕颗粒缓解糖尿病肾病肾纤维化的作用机制。方法以6周龄雄性C57BL/BKS-DB野生型(db/m)小鼠(n=6)和C57BL/BKS-DB(db/db)小鼠(n=30)作为实验对象,db/m小鼠为正常组,db/db小鼠随机分为模型组、阳性对照(氯沙坦钾)组(8.6 mg/kg)及玉蚕颗粒低(1.3 g/kg)、中(2.6 g/kg)、高(5.2 g/kg)剂量组,每组6只。各组小鼠每日灌胃给予相应干预,连续10周。干预结束后,收集血清和肾组织检测小鼠生化指标,采用苏木精-伊红(HE)、马松(Masson)、过碘酸-希夫(PAS)染色法观察各组小鼠肾组织病理损伤,采用酶联免疫吸附分析(ELISA)法对各组肾组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)以及丙二醛(MDA)进行检测分析。原位末端转移酶标记(TUNEL)免疫荧光染色法检测细胞凋亡,免疫组织化学法检测肾组织B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、胱天蛋白酶-3(Caspase-3)。Western blot法检测肾脏I型胶原蛋白(Col-1)、转化生长因子-β1(TGF-β1)。结果①与正常组相比,模型组空腹血糖(FBG)、血肌酐(SCr)、血尿素氮(BUN)、尿微量白蛋白(mALB)、尿白蛋白/肌酐(UACR)水平均显著升高(P<0.01,P<0.001);与模型组相比,玉蚕颗粒各剂量组FBG、SCr、BUN、mALB、UACR水平均有不同程度降低(P<0.05,P<0.01,P<0.001)。②正常组小鼠肾小球完整,边界清晰明确,蓝色胶原纤维沉积较少;模型组小鼠肾脏发生显著形态学变化,可见间质炎症细胞浸润,系膜基质增生、肾小球肥大,大量蓝色胶原纤维沉积,基底膜均质性增厚,系膜基质扩张,侵犯毛细血管管腔。玉蚕颗粒各剂量组胶原纤维阳性面积低于模型组(P<0.01)。③与正常组相比,模型组Col-1、TGF-β1表达升高(P<0.01);各治疗组Col-1、TGF-β1表达均低于模型组,其中玉蚕颗粒中、高剂量组Col-1表达与模型组相比有差异(P<0.01);玉蚕颗粒高剂量组TGF-β1表达与模型组相比有差异(P<0.05)。与正常组�Objective To investigate the mechanism of Yucan Granules on relieving renal fibrosis(RIF)in diabetic kidney disease(DKD)in db/db mice.Methods Six weeks old male C57BL/BKS-DB wild-type(db/m)mice(n=6)and C57BL/BKS-DB(db/db)mice(n=30)were used as experimental subjects.The db/m mice were set as the normal group,and the db/db mice were randomly divided into a model group,a positive control(losartan potassium)group(8.6 mg/kg),and Yucan Granules low(1.3 g/kg),medium(2.6 g/kg),and high(5.2 g/kg)dose groups,with 6 mice in each group.The mice in each group were given the corresponding interventions by gavage every day for 10 consecutive weeks.After the intervention,serum and kidney tissues were collected to detect biochemical indicators of mice.Hematoxylin-eosin(HE),Masson and Periodic Acid-Schiff(PAS)stainings were used to observe the pathological damage of renal tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in renal tissue of each group.Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling(TUNEL)immunofluorescence staining.Immunohistochemistry was employed to detect B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and caspase-3.Type I collagen(Col-1)and transforming growth factor-β1(TGF-β1)in kidney were detected by Western blot.Results①Compared with the normal group,the levels of fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),urinary microalbumin(mALB)and urinary albumin/creatinine(UACR)in the model group were significantly increased(P<0.01,P<0.001);Compared with the model group,the levels of FBG,SCr,BUN,mALB and UACR in each dose group of Yucan Granules were decreased to varying degrees(P<0.05,P<0.01,P<0.001).②In the normal group,the glomeruli of mice were intact,with clear and distinct boundaries,and there was less deposition of blue collagen fibers;In the model group,significant morphological changes occurred in the ki

关 键 词：糖尿病肾病 肾纤维化 玉蚕颗粒 细胞凋亡 氧化应激 中药研究 

分 类 号：R285.5[医药卫生—中药学]