转化生长因子-β1在丹红改善早期慢性肾脏病大鼠肾脏病理损伤中的作用

Role of Transforming Growth Factor β1 in Improving Renal Pathological Lesions of Rats with Early Chronic Kidney Disease with Danhong

目的:探讨中药丹红对早期慢性肾脏病(chronic kidney disease,CKD)大鼠肾脏病理损伤的疗效及TGF-β1在其中的作用。方法:将30只雄性SD大鼠随机分为模型组、对照组和干预组,每组10只。3组大鼠分别给予单侧肾切除建立早期CKD模型、假手术(逐层分离组织至肾包膜,但不做肾切除)和建立早期CKD模型后丹红干预。观察各组大鼠肾脏病理改变、24 h尿蛋白量和肾功能,分别采用酶联免疫吸附试验(ELISA)和免疫组织化学法检测肾皮质中转化生长因子β1(transforming growth factorβ1,TGF-β1)浓度和肾组织总TGF-β1表达情况。结果:与对照组相比,模型组大鼠肾小球轻中度系膜细胞增生伴局部系膜基质增宽、球囊壁粘连及毛细血管壁改变,肾小管间质存在不同程度炎性细胞浸润与间质纤维化;与模型组比较,干预组大鼠肾脏病变明显减轻;模型组的肾脏病理总积分高于对照组(P<0.05),而干预组低于模型组(P<0.05)。模型组与干预组24 h尿蛋白量高于对照组(P<0.01),干预组24 h尿蛋白量低于模型组(P<0.01)。3组血肌酐、尿素水平无显著差异,但模型组和干预组血清半胱氨酸蛋白酶抑制剂浓度较对照组明显增高(P<0.05)。模型组大鼠肾皮质TGF-β1浓度和肾组织总TGF-β1表达水平明显高于对照组(P<0.05),干预组两者均低于模型组(P<0.05)。肾组织TGF-β1表达与尿蛋白量、肾脏病理损伤总积分均有显著相关性(P<0.01)。结论:丹红能通过下调TGF-β1表达改善早期CKD大鼠肾脏病理病变。

Objective：To explore the efficacy of traditional chinese medicine Danhongon renal pathological lesions of rats with early chronic kidney disease（CKD）and the role of transforming growth factor β1（TGF-β1）in it.Methods：Thirty male SD rats were divided into three groups：the early CKD group（model group）,the sham-operated group（control group）and Danhong treated group（treated group）,with10 in each group.Rats in the three groups were treated by uninephrectomy for building up early CKD model,sham-operation（separating tissues to renal capsule without kidney excision）,and Danhongtreatment after building up model,respectively.Renal pathological lesions,24 h urine protein excretion and renal function were observed.The concentration of TGF-β1 in renal cortex and overall expression of TGF-β1 in renal tissue was examined by enzyme-linked immune-sorbent assay（ELISA）and immunohistochemistry,respectively.Results：Mild to moderate proliferation of glomeruli mesangial cells accompanied by broadened mesangium matrix,glomeruli capsule wall adhesion and change of capillary wall,interstitial fibrosis and inflammatory monocytes infiltration was found in the model group other than the control group.Renal lesions were alleviated dramatically in treated group,while compared to that in model group.The gross renal pathological score in model group was higher than that in control group（P〈0.05）,however,the score in treated group was lower than that in model group（P〈0.05）.The 24 h urinary protein excretion in model group and treated group was higher than that in control group（P〈0.01）,while the 24 h urinary protein excretion in treated group was lower than that in model group（P〈0.01）.There was no significant difference among the three groups regarding blood creatinine level and urea level.Serum CysC levels in model group and treated group increased significantly than that in control group（P〈0.05）.The concentration of TGF-β1 in renal cortex and overall expression of TGF-β1 in renal tissue were higher in model group than those in control group（P〈0.05）,while those in treated group were lower than those in model group（P〈0.05）.TGF-β1 expression level in renal tissues was significantly associated with both the urinary protein excretion and the total renal pathological scores（P 0.01）.Conclusions：Danhongalleviated renal pathological lesions by down-regulating TGF-β1 expression.