雷公藤多苷对糖尿病肾病大鼠肾损伤的影响  

Effects of Tripterygium wilfordii multiglycoside on renal injury in rats with diabetic nephropathy

作　　者：张冲 宋纯东[1,2] 王墨[3] 梁爽[1,2] 郭笑笑 张晗寒 李培嘉 宋珂 陈晨晨 ZHANG Chong;SONG Chundong;WANG Mo;LIANG Shuang;GUO Xiaoxiao;ZHANG Hanhan;LI Peijia;SONG Ke;CHEN Chenchen(Second Ward of Nephrotic Purpura,Paediatric Hospital of the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450099,China;College of Pediatrics,Henan University of Chinese Medicine,Zhengzhou 450046,China;Dept.of Nephrology and Immunology,Children’s Hospital of Chongqing Medical University,400042,China)

机构地区：[1]河南中医药大学第一附属医院儿科医院肾病紫癜二病区,郑州450099 [2]河南中医药大学儿科医学院,郑州450046 [3]重庆医科大学附属儿童医院肾脏免疫科,重庆400042

出　　处：《中国药房》2025年第7期815-819,共5页China Pharmacy

基　　金：国家自然科学基金项目(No.82074493);河南省中医药科学研究专项课题(No.2022JDZX003);河南省中医药科学研究重大专项课题(No.2023ZYZD02);河南省中医药学科领军人才项目(No.豫卫中医函[2021]8号);河南省“双一流”创建学科中医学科学研究专项(No.HSRP-DFCTCM-2023-3-07)。

摘　　要：目的基于肿瘤蛋白p53/微RNA-214(miR-214)/UNC-51样激酶1(ULK1)轴探讨雷公藤多苷(TWM)对糖尿病肾病(DN)大鼠肾损伤的影响。方法将雄性SD大鼠分为正常组(6只)和造模组(28只),造模组大鼠以高脂高糖饲料喂养+链脲佐菌素腹腔注射法建立DN模型。将造模成功的大鼠分为模型组、缬沙坦组[8.33 mg/(kg·d)]、TWM组[6.25 mg/(kg·d)],每组8只。各组大鼠灌胃相应药液或生理盐水,每天1次,连续6周。末次给药后,检测各组大鼠尿液/血液中肝肾功能指标[24 h尿蛋白定量(24 hUTP)、血尿素氮(BUN)、血肌酐(SCr)、白蛋白(ALB)、丙氨酸转氨酶(ALT)]、血脂指标(甘油三酯、总胆固醇)、血糖指标(空腹血糖)水平,观察其肾组织病理改变,并检测其肾组织中p53、ULK1、Beclin-1、微管相关蛋白1轻链3(LC3)蛋白及mRNA和miR-214的表达情况。结果与正常组比较,模型组大鼠肾小管上皮水肿明显,细胞肿胀,伴有淋巴细胞浸润;模型组和各药物组大鼠24 hUTP、BUN、SCr、ALT和糖脂指标水平,p53蛋白及m RNA和miR-214的表达均显著升高或上调,而ALB水平、LC3-Ⅱ/LC3-Ⅰ、LC3 mRNA、ULK1、Beclin-1蛋白及mRNA的表达均显著降低或下调(P<0.01)。与模型组比较,各药物组大鼠肾组织病理学损伤均有所好转;其24 h-UTP、BUN、SCr、ALT和糖脂指标水平,p53蛋白及mRNA和miR-214的表达均显著降低或下调,而ALB水平、LC3-Ⅱ/LC3-Ⅰ、LC3 mRNA、ULK1、Beclin-1蛋白及mRNA的表达均显著升高或上调(P<0.01)。结论TWM能减轻DN大鼠的肾损伤,改善其肝肾功能和糖脂水平,上述作用可能与调控p53/miR-214/ULK1轴、恢复细胞自噬有关。OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside(TWM)on renal injury in diabetic nephropathy(DN)rats through tumor protein p53/microRNA-214(miR-214)/UNC-51-like kinase 1(ULK1)axis.METHODS Male SD rats were randomly divided into normal group(n=6)and modeling group(n=28);the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model.The modeled rats were randomly divided into model group,valsartan group[8.33 mg/(kg·d)]and TWM group[6.25 mg/(kg·d)],with 8 rats in each group.Rats in each group were gavaged with the corresponding medication or normal saline,once a day,for 6 consecutive weeks.After the last medication,liver and renal function indexes[24 h urinary total protein(24 h-UTP),blood urea nitrogen(BUN),serum creatinine(SCr),albumin(ALB),alanine transaminase(ALT)],blood lipid indexes(triglycerides,total cholesterol)and blood glucose index(fasting blood glucose)in urine/blood sample of rats were detected in each group.Renal pathologic change was observed,protein and mRNA expressions of p53,ULK1,Beclin-1 and microtubule-associated protein 1 light chain 3(LC3),and expression of miR-214 in renal tissue were also determined.RESULTS Compared with the normal group,the renal tubular epithelium of rats in the model group showed obvious edema,cell swelling,accompanied by lymphocyte infiltration;the levels of 24 h-UTP,BUN,SCr,ALT and glycolipid indexes,the expressions of p53 protein and mRNA,as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated,while ALB level,LC3-Ⅱ/LC3-Ⅰ,the expressions of LC3 mRNA,the expressions of ULK1,Beclin-1 protein and mRNA were significantly decreased or down-regulated(P<0.01).Compared with the model group,the histopathological damage of the kidney in rats was improved in administration groups;the levels of 24 h-UTP,BUN,SCr,ALT and glycolipid indexes,the expressions of p53 protein and mRNA,as well as the expression of

关 键 词：雷公藤多苷 糖尿病肾病 肾损伤 自噬 p53/miR-214/ULK1轴 

分 类 号：R965[医药卫生—药理学] R285.5[医药卫生—药学]