苦瓜皂苷G通过调控Notch/Snail1信号通路改善糖尿病肾病大鼠肾功能减退及肾纤维化  

Momordica Charantia L. Saponins G Improves Renal Dysfunction and Renal Fibrosis in Diabetic Nephropathy Rats Through Regulating Notch/Snail1 Signaling Pathway

作　　者：尤云[1] 洪丽萍 韩羽 YOU Yun;HONG Li-Ping;HAN Yu(Hemodialysis Room,The Affiliated Hospital of Xinyang Vocational and Technical College,Xinyang 464000 Henan,China;Dept.of Nephrology,Zhengzhou Yihe Hospital,Zhengzhou 450000 Henan,China;Dept.of Nephrology,Nanyang Second General Hospital,Nanyang 473000 Henan,China)

机构地区：[1]信阳职业技术学院附属医院血液透析室,河南信阳464000 [2]郑州颐和医院肾内科,河南郑州450000 [3]南阳市第二人民医院肾内科,河南南阳473000

出　　处：《广州中医药大学学报》2023年第4期943-949,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20191479)。

摘　　要：【目的】观察苦瓜皂苷G对糖尿病肾病(DN)大鼠的治疗作用及机制。【方法】从55只大鼠中随机抽取45只采用一次性腹腔注射链脲佐菌素(STZ)法诱导DN模型。将造模成功的38只大鼠随机分为模型组9只、苦瓜皂苷G低剂量组9只、苦瓜皂苷G中剂量组10只、苦瓜皂苷G高剂量组10只。剩余10只大鼠设为正常组。对应灌胃给药4周后,酶联免疫吸附分析(ELISA)检测大鼠24 h尿蛋白水平,血糖仪检测空腹血糖(FBG),全自动生化分析仪检测血肌酐(SCr)、血尿素氮(BUN)水平,苏木素-伊红染色(HE)法观察大鼠肾组织病理学变化,采用实时定量聚合酶链反应(RT-qPCR)和Western Blot法分别检测E-钙黏蛋白(E-cad)、α-平滑肌肌动蛋白(α-SMA)、Notch1、锌指蛋白转录因子1(Snail1)、Jagged1 m RNA及蛋白表达情况。【结果】与正常组比较,模型组24 h尿蛋白、FBG、血清SCr和BUN水平及肾组织α-SMA、Notch1、Snail1、Jagged1 mRNA及蛋白水平显著升高,肾组织E-cad m RNA及蛋白水平降低,肾组织可见肾小球萎缩、肾小管扩张及间质纤维化;与模型组比较,苦瓜皂苷G低、中、高剂量组24 h尿蛋白、FBG、血清SCr和BUN水平及肾组织α-SMA、Notch1、Snail1、Jagged1 mRNA及蛋白水平显著降低,肾组织E-cad m RNA及蛋白水平升高,肾组织病理损伤得到改善。【结论】苦瓜皂苷G可有效改善DN大鼠肾功能障碍、减轻肾脏纤维化,其机制可能与通过调控Notch/Snail1信号通路,抑制α-SMA和Jagged1 mRNA及蛋白表达,增强E-cad mRNA及蛋白表达有关。Objective To observe the therapeutic effect and mechanism of Momordica Charantia L. saponins G on diabetic nephropathy(DN)rats. Methods Forty-five rats were randomly selected from 55 rats to induce the DN model using a single intraperitoneal injection of streptozotocin(STZ). The 38 rats with successful modelling were randomly divided into 9 rats in the model group, 9 rats in the Momordica Charantia L. saponins G low-dose group, 10 rats in the Momordica Charantia L. saponins G medium-dose group and 10 rats in the Momordica Charantia L. saponins G high-dose group. The remaining 10 rats were set as the normal group. After 4 weeks of intragastric administration,the 24-hour urinary protein levels were measured by enzyme-linked immunosorbent assay(ELISA), fasting blood glucose(FBG)by glucometer, serum creatinine(SCr)and blood urea nitrogen(BUN)by automatic biochemical analyzer,and renal histopathological changes were observed by hematoxylineosin staining(HE),real-time quantitative polymerase chain reaction(RT-qPCR)and Western Blot were used to detect mRNA and protein expressions of E-cadherin(E-cad),α-smooth muscle actin(α-SMA),Notch1,Notch/zinc finger protein transcription factor 1(Snail1)signaling pathway, respectively. Results Compared with the normal group, 24-hour urinary protein, FBG, serum SCr and BUN levels, mRNA and protein levels of α-SMA,Notch1,Snail1 and Jagged1 in renal tissue were significantly increased in the model group,while mRNA and protein levels of E-cad in renal tissue were decreased. Renal tissue showed glomerular atrophy, tubule dilatation and interstitial fibrosis. Compared with the model group,24-hour urinary protein,FBG,serum SCr and BUN levels, mRNA and protein levels of α-SMA, Notch1, Snail1 and Jagged1 in kidney tissue of Momordica Charantia L. saponins G low-dose,medium-dose and high-dose groups were significantly decreased,while m RNA and protein levels of E-cad in kidney tissue were increased,and the pathological injury of kidney tissue was improved. Conclusion Momordica Charantia L

关 键 词：苦瓜皂苷G 糖尿病肾病 Notch/锌指蛋白转录因子1(Snail1)信号通路 E-钙黏蛋白(E-cad) α-平滑肌肌动蛋白(α-SMA) JAGGED1 大鼠 

分 类 号：R285.5[医药卫生—中药学]