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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 in rats after unilateral ureteral obstruction (UUO). Methods Forty-eight Sprague-Dawley rats were randomly divided into four groups (12 rats in each group): Sham group, UUO model group, Thd200mg.kg-1.d-1 treatment group and Thd group Lobotin New 10 mg.kg-1.d-1 treatment group (Lot group). Renal function was detected by blood at 7 and 14 days after operation. Renal interstitial lesions were observed by Masson staining. HIF-1α, ColⅠ and α- Actin (α-SMA) expression. Results Compared with Sham group, the levels of blood urea nitrogen and creatinine, the degree of renal interstitial fibrosis and the expressions of HIF-1α, α-SMA and ColⅠ in UUO group were significantly increased (P <0.01). The above indexes (P <0.01). Compared with UUO group, all the other indexes in Lot group were lower than those in UUO group (P <0.01), except for HIF-1α expression, and there was no significant difference between Thu group and UUO group (P> 0.05). Conclusion Thd can improve renal function, and may inhibit the renal tubular epithelial cell transdifferentiation and renal interstitial extracellular matrix accumulation by down-regulating the expression of HIF-1α.