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目的观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对单侧输尿管梗阻(UUO)所致大鼠肾间质纤维化的的改善作用并探讨其机制。方法将雄性Wistar大鼠36只随机分为假手术组,UUO组,处理组(AcSDKP+UUO),每组各12只。于造模第3、14d各处死大鼠6只,取其梗阻侧肾脏组织行HE染色,光镜下观察肾组织病理改变,计算肾间质纤维化指数。免疫组织化学方法检测其各组肾脏组织转化生长因子β1(transforming growth factor-β1,TGF-β1)及a平滑肌肌动蛋白(a-smooth muscle actin,a-SMA)表达,RT-PCR方法检测TGF-β1及a-SMA mRNA含量。结果与假手术组相比,各时间点UUO组大鼠肾脏病理损害进行性加重,AcSDKP处理后可明显减轻UUO组大鼠肾间质纤维化程度(P<0.05);免疫组化染色及RT-PCR显示:TGF-β1、a-SMA的蛋白及mRNA表达UUO组和处理组明显多于假手术组,但处理组较UUO组明显减轻(P<0.05)。结论 N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)可通过抑制TGF-β1及a-SMA表达,进而抑制大鼠肾间质纤维化,减缓肾纤维化的病程进展。
Objective To investigate the effect of AcSDKP on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in rats and to explore the mechanism of N-acetyl-seryl-aspartyl-lysyl-proline . Methods Thirty-six male Wistar rats were randomly divided into sham operation group, UUO group and AcSDKP + UUO group, 12 rats in each group. Six rats were sacrificed on the third and the 14th day respectively, and the obstructed kidney tissues were harvested for HE staining. The renal pathological changes were observed under light microscope and the index of renal interstitial fibrosis was calculated. The expression of transforming growth factor-β1 (TGF-β1) and a-smooth muscle actin (a-SMA) in renal tissues was detected by immunohistochemical method. -β1 and a-SMA mRNA content. Results Compared with the sham-operation group, the renal pathological changes of rats in UUO group increased significantly at each time point. AcSDKP treatment significantly reduced the degree of renal interstitial fibrosis in rats in UUO group (P <0.05). Immunohistochemical staining and RT-PCR -PCR showed that the protein and mRNA expression of TGF-β1 and a-SMA in UUO group and treated group were more than that in sham-operated group, but the treatment group was significantly lower than UUO group (P <0.05). Conclusion AcSDKP can inhibit renal interstitial fibrosis and slow down renal fibrosis by inhibiting the expression of TGF-β1 and a-SMA in N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) The course of the disease.