【摘要】 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。更多还原

【Abstract】 Objective:To investigate the protective effect of Acetyl-Ser-Asp-Lys-Pro (AcSDKP)on unilateral ureteral obstruction induced renal interstitial fibrosis in rats and its mechanism.Methods:Eighteen male Wistar rats were randomly divided into the sham-operated group,the UUO group and the AcSDKP treated group.Animal models of renal interstitial fibrosis were established with unilateral ureteral ligation in rats.Rats were sacrificed after 14 days of the surgery.Histological change of the obstructed kidney was observed by HE and Masson stain.The protein expression and localization of Monocyte Chemoattractant Protein-1 (MCP-1),ED-1 and nuclear factor-kappa B(NF-κB )in renal tissues were detected with immunohistochemical staining.The mRNA levels of MCP-1 was analyzed with reverse transcription-polymerase chain reaction.Protein expression of NF-κB was assessed by Western Blot.Results:Compared with the sham-operated group,the UUO group exhibited severe renal interstitial fibrosis and markedly higher expressions of MCP-1,ED-1 and NF-κB (P<0.05),while renal interstitial fibrosis was less marked and levels of MCP-1 ED-1 and NF-κB were down-regulated significantly in the AcSDKP group (P<0.05).Conclusion:AcSDKP relieved renal interstitial fibrosis by inhibiting NF-κB activation to reduce the expression of inflammatory cytokines.更多还原