摘要
目的:探究金丝桃苷(HP)对糖尿病肾病(DN)大鼠转化生长因子-β1(TGF-β1)/smad通路及肾上皮间质转化(EMT)的影响。方法:采用高脂饲料喂养及腹腔注射链脲佐菌素(STZ)构建DN大鼠模型,随机分为模型(M)组、阳性药物罗格列酮(RGZ)组、HP低(HP-L)、中(HP-M)、高剂量(HP-H)组,每组12只;另取正常非DN大鼠12只为对照组(NC组),按照各组给药剂量连续灌胃处理8周。采集各组大鼠血清、24 h尿液及双侧肾组织,检查24 h尿微量白蛋白(UAlb)变化及空腹血糖(FBG)、尿肌酐(Ucr)、尿素氮(BUN)水平;苏木精—伊红染色(HE)观察大鼠肾脏组织病理变化;Masson染色分析大鼠肾脏纤维化程度;免疫印记法检测肾组织EMT、TGF-β1/smad通路相关蛋白表达情况。结果:与NC组比较,M组大鼠FBG、UAlb、Ucr、BUN水平显著升高(P<0.05),肾组织病变严重,肾小球体积显著增大,肾脏纤维化面积显著增多,肾组织E-钙黏蛋白(E-cadherin)、smad7蛋白水平显著降低,α-平滑肌动蛋白(α-SMA)、纤维连接蛋白(Fibronectin)、TGF-β1、smad2、smad3蛋白水平显著升高(P<0.05);与M组比较,HP-L组、HP-M组、HP-H组大鼠FBG、UAlb、Ucr、BUN水平均显著降低,肾组织病变及肾纤维化程度得到一定改善,肾组织E-cadherin、smad7蛋白水平显著升高(P<0.05),α-SMA、Fibronectin、TGF-β1、smad2、smad3蛋白水平显著降低,且呈剂量依赖性(P<0.05)。结论:HP可减轻DN大鼠肾脏纤维化、抑制EMT过程,可能与抑制TGF-β1/smad通路有关。
Objective: To investigate the effects of hypericin(HP) on transforming growth factor-β1(TGF-β1)/Smad pathway and renal epithelial-mesenchymal transition(EMT) in diabetic nephropathy(DN) rats. Methods:DN rat model was established by feeding with high-fat dietand intraperitoneal injection of streptozotocin(STZ).The DN ratswere randomly divided into model(M) groupand HP low-dose(HP-L), medium-dose(HP-M), and high-dose(HP-H) groups, with 12 rats in each group. Twelve healthy rats were selected as a control group(NC group). The drugs were given by gavage for 8 weeks. The serum, 24-hour urine and bilateral renal tissues were collected. The 24-hour urine microalbumin(UAlb), fasting blood glucose(FBG), urine creatinine(Ucr), and urea nitrogen(BUN) levels were detected. Hematoxylin eosin(HE) staining was used to observe the pathological changes of rat kidney tissue. Masson staining was used to analyze the degree of rat kidney fibrosis. Immunoblotting method was used to detect the expression of EMT and TGF-β1/smad pathway related proteins in kidney tissue. Results: Compared with NC group, the renal tissue was severely diseasedin M group. The levels of FBG, UAlb, Ucr and BUN, the glomerular volume, the area of renal fibrosis and the protein levels of α-SMA, Fibronectin, TGF-β1, smad2 and smad 3 were significantly increased, while the protein levels of Ecadherin and smad7 were significantly decreased in M group(P<0.05). Compared with M group, the renal tissue lesions and renal fibrosis were improved to some extent in HP groups. The levels of FBG, UAlb, Ucr and BUN and the protein levels of α-SMA, Fibronectin, TGF-β1, smad2 and smad3 were markedly decreased, whereas the protein levels of E-cadherin and smad7 in renal tissues were significantly increased in HP groups in a dose-dependent manner(P<0.05). Conclusion: HP can alleviate renal fibrosis and inhibit EMT in DN rats, and it may be related to the inhibition of TGF-β1/smad pathway.
作者
王苑菲
沈美晓
吴祖荣
黄亚莲
琚枫
符畅
符茂雄
Wang Yuanfei;Shen Meixiao;Wu Zurong;Huang Yalian;Ju Feng;Fu Chang;Fu Maoxiong(Department of Endocrinology and Metabolism,The Second Affiliated Hospital of Hainan Medical University,Haikou 570100,China)
出处
《广西医科大学学报》
CAS
2021年第9期1654-1660,共7页
Journal of Guangxi Medical University
基金
海南自然科学基金资助项目(No.817333)。
关键词
糖尿病肾病大鼠
金丝桃苷
转化生长因子-Β1
上皮间质转化
diabeticnephropathy rats
hyperoside
transforming growth factor-β1
epithelial-mesenchymal transition
