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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保护作用并初探其机制。方法:雄性Wistar大鼠18只,随机分为假手术组、UUO组、治疗组(AcSDKP+UUO),每组各6只。于造模第14天处死大鼠,取其梗阻侧肾脏组织行HE、Masson染色,光镜下观察肾组织病理改变,评价肾小管变性程度及肾间质纤维化指数,免疫组织化学检测各组肾脏组织MCP-1、ED-1及NF-κB蛋白表达,RT-PCR检测MCP-1 mRNA的表达,Western blot检测NF-κB的蛋白质表达。结果:与假手术组相比,UUO组大鼠肾脏肾小管变性及肾间质纤维化程度严重,AcSDKP治疗后可明显改善UUO组大鼠肾小管变性和间质纤维化(P<0.05);免疫组化染色显示:MCP-1、ED-1及NF-κB的蛋白表达UUO组和治疗组明显多于假手术组,但治疗组较UUO组明显减少(P<0.05);AcSDKP治疗组MCP-1 mRNA及NF-κB蛋白质的表达均显著弱于UUO组,二者相比差异有统计学意义(P<0.05)。结论:AcSDKP通过抑制NF-κB激活并进一步减少下游炎症细胞因子的表达以达到治疗肾间质纤维化的作用。
AIM: To investigate the protective effect of AcSDKP on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in rats mechanism. Methods: Eighteen male Wistar rats were randomly divided into sham operation group, UUO group and treatment group (AcSDKP + UUO), 6 rats in each group. Rats were sacrificed on the 14th day after operation, and obstructed kidney tissues were harvested for HE and Masson staining. The pathological changes of renal tissues were observed under light microscope. The extent of renal tubular degeneration and renal interstitial fibrosis index were evaluated. Immunohistochemistry The expressions of MCP-1, ED-1 and NF-κB in renal tissue were detected by RT-PCR. The protein expression of NF-κB was detected by Western blot. Results: Compared with the sham - operated group, renal tubular degeneration and renal interstitial fibrosis in UUO group were severe. AcSDKP treatment could significantly ameliorate renal tubular degeneration and interstitial fibrosis in UUO group (P <0.05). Immunohistochemical staining showed that the expression of MCP-1, ED-1 and NF-κB in UUO group and treatment group were significantly more than those in sham operation group, but the treatment group was significantly lower than UUO group (P <0.05); AcSDKP treatment group MCP 1 mRNA and NF-κB protein expression were significantly weaker than UUO group, the difference was statistically significant (P <0.05). Conclusion: AcSDKP can treat renal interstitial fibrosis by inhibiting NF-κB activation and further reducing the expression of downstream inflammatory cytokines.