大车前苷对糖尿病大鼠肾纤维化的干预作用  

Interventional Effect of Plantamajoside on Renal Fibrosis in Diabetic Rats

作　　者：梁霄 王盼[2] 李涛[3] 牛昭 陈婧[4] LIANG Xiao;WANG Pan;LI Tao;NIU Zhao;CHEN Jing(Dept.of Nephrology Rheumatology,the No.2 Hospital of Baoding,Raoding 071000 Hebei,China;Dept.of Pathology,Affiliated Hospital of Hebei University,Baoding 071030 Hehei,China;Dept.of Clinical Lab,the No.2 Hospital of Baoding,Baoding 071000 Hebei,China;Dept.of Oncology,the No.2 Central Hospital of Baoding,Baoding 071000 Hebei,China)

机构地区：[1]保定市第二医院肾内科风湿免疫科,河北保定071000 [2]河北大学附属医院病理科,河北保定071030 [3]保定市第二医院检验科,河北保定071000 [4]保定市第二中心医院肿瘤科,河北保定071000

出　　处：《广州中医药大学学报》2021年第12期2729-2736,共8页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：保定市科学技术研究与发展指导计划项目(编号:18ZF109)。

摘　　要：【目的】探讨大车前苷对糖尿病大鼠肾纤维化的干预作用。【方法】将新生大鼠随机分为正常组,模型组,大车前苷低、中、高剂量组,二甲双胍组,每组6只。除正常组外,其他各组大鼠出生第2天给予单次腹膜内注射链脲佐菌素(STZ)构建糖尿病模型。第12~16周,大车前苷低、中、高剂量组大鼠分别对应灌胃大车前苷10、20、40 mg·kg^(-1)·d^(-1),二甲双胍组灌胃二甲双胍25 mg·kg^(-1)·d^(-1)。给药结束后,进行血液和尿液生化检测,进行肾组织氧化应激指标检测,采用苏木素-伊红(HE)染色法观察肾脏病理变化,采用免疫组织化学法检测肾组织中转化生长因子(TGF)-β水平,采用蛋白免疫印迹法检测肾组织α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)、TGF-β、Smad2、Smad3和Smad7蛋白表达水平。【结果】与正常组比较,模型组大鼠血糖含量及总胆固醇(TC)、甘油三酯(TG)、尿素氮(BUN)、血清肌酐(SCr)水平显著升高,胰岛素、总蛋白(TP)和白蛋白(ALB)水平均显著降低,尿液中尿蛋白(PRO)、潜血(BLO)和胆红素(BIL)含量均显著增加(均P<0.01),肾组织可见明显纤维化改变,肾组织丙二醛(MDA)水平显著升高,还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽转移酶(GST)、超氧化物歧化酶(SOD)水平均显著降低,肾组织TGF-β的PI值显著升高,E-cadherin和Smad7表达水平显著下调,α-SMA、 TGF-β、 Smad2和Smad3表达水平均显著上调(均P<0.01)。与模型组比较,大车前苷中、高剂量组和二甲双胍组上述指标均得到明显改善(P<0.05或P<0.01),大车前苷低剂量组则改善不明显(P> 0.05)。【结论】大车前苷可能通过调节氧化应激及TGF-β/Smad信号通路抑制糖尿病大鼠肾纤维化。Objective To explore the prevention effect of Plantamajoside on renal fibrosis in diabetic rats. Methods The newborn rats were randomly divided into normal group, model group, and low-dose, medium-dose and high-dose Plantamajoside groups,with 6 rats in each group. Except for the normal group,all groups were given a single intraperitoneal injection of streptozotocin(STZ)on the second day of life to construct a diabetic model. From week 12 to 16,rats in the low-,medium-and high-dose Plantamajoside groups were given 10,20,40 mg·kg-1·d-1 of Plantamajoside by gavage,respectively,and the metformin group was given 25 mg·kg-1·d-1 of metformin by gavage. At the end of the dosing period,blood and urine biochemical tests were carried out,and renal tissue oxidative stress indexes were measured,and renal pathological changes were observed by hematoxylin-eosin(HE)staining. Immunohistochemistry was used to detect transforming growth factor(TGF)-β level in renal tissues,and Western Blot was used to detect α smooth muscle actin(α-SMA),E-cadherin,TGF-β,Smad2,Smad3 and Smad7 protein expression levels in renal tissues. Results Compared with the normal group,blood glucose level and total cholesterol(TC), triglyceride(TG), urea nitrogen(BUN) and serum creatinine(SCr) levels were significantly increased in the model group, and insulin, total protein(TP)and albumin(ALB)levels were significantly decreased,while the levels of urinary protein(PRO),octetic blood(BLO)and bilirubin(BIL)in the urine were significantly increased in the model group(all P < 0.01), and the renal tissue showed significant fibrosis changes. The level of malondialdehyde(MDA)was significantly increased, and the levels of reduced glutathione(GSH),glutathione peroxidase(GPx),glutathione transferase(GST)and superoxide dismutase(SOD)were significantly decreased, and the PI value of TGF-β was significantly increased in renal tissue, while E-cadherin and Smad7 expression levels were significantly down-regulated,and α-SMA,TGF-β,Smad2 and Smad3 expression levels we

关 键 词：大车前苷 糖尿病 肾纤维化 氧化应激 TGF-Β/SMAD信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]