莱菔硫烷对单侧输尿管梗阻所致小鼠肾纤维化的干预作用及其机制  

Interventional effect and mechanism of sulforaphane on renal fibrosis induced by unilateral ureteral obstruction in mice

作　　者：郭莉[1] 龚幼兰[1] 李晶[1] 任茜[2] 郝捷[2] GUO Li;GONG Youlan;LI Jing;REN Qian;HAO Jie(The Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院,河北保定071000 [2]保定市第二医院

出　　处：《山东医药》2019年第32期33-36,共4页Shandong Medical Journal

基　　金：河北省保定市科学技术研究与发展指导计划项目(18ZF060)

摘　　要：目的观察莱菔硫烷对单侧输尿管梗阻(UUO)所致小鼠肾纤维化的干预作用,并探讨其机制。方法将32只小鼠随机分为Sham组、Sham+SFN组、UUO组、UUO+SFN组,每组8只。UUO组、UUO+SFN组通过UUO手术制作肾纤维化模型,Sham组、Sham+SFN组进行手术但不结扎输尿管。手术后第2天UUO+SFN组、Sham+SFN组腹膜内注射莱菔硫烷25 mg/(kg·d),Sham组、UUO组给予等量的生理盐水,持续给药至第14天。实验第14天时心脏采血获取血清,检测血肌酐和BUN;取小鼠肾脏组织,测量肾脏质量、肾脏指数,HE染色和Masson三色染色观察肾脏组织学变化并进行损伤评分,显微镜下观测肾间质纤维化面积,PSR染色评价间质胶原沉积情况,IHC染色检测胶原蛋白Ⅰ和纤连蛋白,Western blotting法检测TGF-β、p-Smad、t-Smad、结缔组织生长因子(CTGF)。结果UUO组肾脏质量和肾脏指数低于Sham组,UUO+SFN组肾脏质量和肾脏指数高于UUO组(P均<0.05)。UUO组小鼠血肌酐、BUN水平高于Sham组,UUO+SFN组血肌酐、BUN水平低于UUO组(P均<0.01)。UUO组肾小管损伤评分、纤维化面积、PSR阳性面积、胶原蛋白Ⅰ及纤连蛋白表达高于Sham组,UUO+SFN组上述指标均低于UUO组(P均<0.01)。UUO组TGF-β、p-Smad、t-Smad、CTGF相对表达量高于Sham组,UUO+SFN组TGF-β、p-Smad、t-Smad、CTGF相对表达量低于UUO组(P均<0.01)。结论莱菔硫烷可减轻UUO所致小鼠肾纤维化,作用机制可能与抑制TGF-β通路信号转导有关。Objective To investigate the protective effect of sulforaphane on unilateral ureteral occlusion(UUO)-induced renal fibrosis in mice.Methods Thirty-two mice were randomly divided into the Sham group,Sham+SFN(sulforaphane,SFN)group,UUO group,and UUO+SFN group,with 8 rats in each group.The mice in the UUO group and the UUO+SFN group were subjected to UUO surgery to prepare the renal fibrosis models,and the mice in the Sham group and the Sham+SFN group were treated without ligating the ureter.On the 2nd day after surgery,the mice in the UUO+SFN group and Sham+SFN group were intraperitoneally injected with lysine 25 mg/(kg·d),and Sham group and UUO group were given the same amount of normal saline until the 14th day.On the 14th day of the experiment,blood was collected from the heart to obtain serum,and serum creatinine and BUN were detected.The kidney tissues of the mice were taken,the kidney mass and kidney index were measured,and the histological changes of the kidney were observed by HE staining and Masson's trichrome staining,and the lesion score was scored.The renal interstitial fibrosis area was measured under the microscope.Type I collagen and fibronectin were detected by PSR(Picric Acid-Sirius Red Staining,PSR)staining and IHC staining,and transforming growth factor-β(TGF-β),p-Smad,t-Smad and connective tissue growth factor(CTGF)were detected by Western blotting.Results The kidney quality and kidney index of the UUO group were lower than those of the Sham group;the kidney mass and kidney index of the UUO+SFN group were higher than those of the UUO group(all P<0.05).The levels of serum creatinine and BUN in the UUO group were higher than those in the Sham group;the levels of serum creatinine and BUN in the UUO+SFN group were lower than those in the UUO group(all P<0.01).The renal tubular injury score,fibrosis area,PSR positive area,type I collagen and fibronectin expression in the UUO group were higher than those in the Sham group;the above indexes in the UUO+SFN group were lower than those in the UUO group

关 键 词：莱菔硫烷 肾纤维化 单侧输尿管梗阻 TGF-β蛋白 SMAD蛋白 

分 类 号：R692.6[医药卫生—泌尿科学]