沙利度胺对单侧输尿管梗阻后大鼠肾间质纤维化的影响  

Effect of thalidomide on renal interstitial fibrosis after unilateral ureteral obstruction in rats

作　　者：罗燕萍[1] 李晶[2] 芮金兵[2] 何建强[1] 王晓明[1] 

机构地区：[1]江苏大学附属医院肾脏病科,江苏省212001 [2]江苏大学附属医院风湿内科,江苏省212001

出　　处：《江苏医药》2012年第1期9-11,共3页Jiangsu Medical Journal

基　　金：江苏大学临床医学科技发展基金项目(JLY20080010)

摘　　要：目的研究沙利度胺(Thd)对单侧输尿管梗阻(UUO)后大鼠肾间质纤维化的作用。方法 48只SD大鼠随机均分为四组,每组12只:假手术组(Sham组)、UUO模型组(UUO组)、Thd200mg.kg-1.d-1治疗组(Thd组)和洛丁新10mg.kg-1.d-1治疗组(Lot组)。术后7、14d取血检测肾功能,Masson染色观察肾间质病变,免疫组织化学和RT-PCR检测肾组织缺氧诱导因子1α(HIF-1α)、Ⅰ型胶原(ColⅠ)及α-平滑肌肌动蛋白(α-SMA)表达。结果与Sham组比较,UUO组血尿素氮和肌酐水平、肾间质纤维化程度以及HIF-1α、α-SMA、ColⅠ蛋白及mRNA表达均明显增加(P<0.01);Thd组上述各观察指标均较UUO组减少(P<0.01);除HIF-1α表达外,Lot组其余指标均较UUO组下降(P<0.01),且与Thd组比较差异无统计学意义(P>0.05)。结论 Thd可改善肾功能,并可能通过下调HIF-1α表达而抑制肾小管上皮细胞转分化和肾间质细胞外基质积聚,进而发挥肾保护作用。Objective To investigate the effect of thalidomide（Thd） on renal interstitial fibrosis after unilateral ureteral obstruction（UUO） in rats. Methods Forty-eight SD rats were randomly divided into four groups of Sham（sham operated）,UUO（UUO model）,Thd（treated with Thd 200mg·kg-1·d-1） and Lot（treated with lotensin 10mg·kg-1·d-1） with 12 rats each.On the 7th and 14th day after surgery,the blood samples were collected for renal function assay and the pathology of renal interstitial tissue was observed by Masson staining.The expressions of hypoxia inducible factor-1α（HIF-1α）,Collagen type I（ColⅠ） and α-smooth muscle actin（α-SMA） in renal tissues were detected by immunohistochemistry and RT-PCR. Results Compared with Sham group,the levels of blood urea nitrogen and serum creatinine,the degree of renal interstitial fibrosis,the protein and mRNA expressions of HIF-1α,ColⅠ and α-SMA were all significantly increased in UUO group（P0.01）.Each index above in Thd group was lower than that in UUO group（P0.01）.Except for the expression of HIF-1α,the other indexes in Lot group were also lower than those in UUO group（P0.01）,and there was no significant difference between Thd group and Lot group（P0.05）. Conclusion Thd may improve renal function and protect the kidney by inhibiting transition of renal tubular epithelium and accumulation of extracellular matrix in the renal interstitium via down-regulating the expression of HIF-1α.

关 键 词：沙利度胺 肾间质纤维化 缺氧诱导因子1Α Α-平滑肌肌动蛋白 

分 类 号：R692[医药卫生—泌尿科学]