【摘要】 目的 探讨毛兰素对糖尿病肾病（diabetic nephropathy,DN）大鼠肾纤维化的影响及调节机制。方法 雄性SD大鼠分为对照组、模型组、地塞米松组、维替泊芬组、毛兰素低剂量组、毛兰素高剂量组以及毛兰素联合地塞米松用药组，每组10只。检测大鼠微量白蛋白尿（microalbuminuria,MAU）和肾功能相关指标水平；观察肾组织病理变化及胶原纤维沉积；检测肾组织中丙二醛和超氧化物歧化酶（superoxide dismutase,SOD）水平；实时定量荧光定量聚合酶链反应检测肿瘤坏死因子（tumor necrosis factor,TNF）-α、白介素（interleukin,IL）-1β、转化生长因子（transforming growth factor,TGF）-β₁信使（messenger,m）RNA水平；免疫印迹法检测Yes相关蛋白（Yes-associated protein,YAP）/PDZ结合基序的转录共激活因子（transcriptional co-activator with PDZ-binding motif,TZA）、结缔组织生长因子（connective tissue growth factor,CTGF）、纤连蛋白（fibronectin,FN）以及纤溶酶原激活物抑制剂（plasminogen activator inhibitor-1,PAI）-1蛋白表达。结果 与对照组相比，模型组和地塞米松组的MAU、血清肌酐（serum creatinine,Scr）、血尿素氮（blood urea nitrogen,BUN）、丙二醇、TNF-α、IL-1β、TGF-β₁mRNA水平及YAP、TAZ、CTGF、FN、PAI-1蛋白表达均升高，SOD活性降低（P <0.05）；与模型组相比，维替泊芬组和毛兰素组的MAU、Scr、BUN、丙二醇、TNF-α、IL-1β、TGF-β₁ mRNA水平及YAP、TAZ、CTGF、FN、PAI-1蛋白表达均降低，SOD活性升高（P <0.05）；回补实验加入地塞米松后显示，高剂量毛兰素对DN大鼠的保护作用被逆转（P <0.05）。结论 毛兰素可通过抑制YAP/TAZ信号通路减轻DN大鼠的肾纤维化。更多还原

【Abstract】 Objective To investigate the effects of erianin on renal fibrosis in diabetic nephropathy（DN） rats and its regulatory mechanism. Methods All male SD rats were divided into control group, model group, dexamethasone group,vertepofin group, low-dose erianin group, high-dose erianin group and erianin combined with dexamethasone group,with 10 rats in each group. The levels of microalbuminuria（MAU） and renal function were detected. The renal tissue pathological changes and collagen fibers deposition were observed. The levels of malondialdehyde（MDA） and superoxide dismutase（SOD） in renal tissue were detected. Real-time quantitative polymerase chain reaction was used to detect tumor necrosis factor（TNF）-α, interleukin（IL）-1β and transforming growth factor（TGF）-β₁ mRNA level. Western blotting was used to detect the Yes-associated protein（YAP）/transcriptional co-activator with PDZ-binding motif（TZA）, connective tissue growth factor（CTGF）, fibronectin（FN）, and plasminogen activator inhibitor-1（PAI-1） protein expression. Results Compared with the control group, MAU, serum creatinine（Scr）, blood urea nitrogen（BUN）, propylene diol content,messenger（m）RNA levels of TNF-α, IL-1β, TGF-β₁ and protein expression of YAP, TAZ, CTGF, FN, PAI-1 in model group and dexamethasone group were increased, while SOD activity was decreased（P<0.05）. Compared with model group, MAU, Scr, BUN, propanediol content, mRNA levels of TNF-α, IL-1β, TGF-β₁ and protein expression of YAP, TAZ,CTGF, FN and PAI-1 in vertepofin group and erianin group were decreased, while SOD activity was increased（P<0.05）.After dexamethasone was added in the supplement experiment, the protective effect of high dose of erianin on DN rats was reversed（P<0.05）. Conclusion Erianin can alleviate renal fibrosis in DN rats by inhibiting YAP/TAZ signaling pathway.更多还原