【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。更多还原

【Abstract】 Objective To investigate the effect and mechanism of the short peptide acetyl-Ser-Asp-Lys-Pro(AcSDKP) on renal interstitial fibrosis induced by unilateral ureteral obstruction in rats.Methods Thirty-six male Wistar rats were randomly divided into sham-operation group,unilateral ureteral obstruction(UUO) group,and UUO+AcSDKP treatment group.Animal model of rat renal interstitial fibrosis was established by unilateral ureteral ligation.Rats were sacrificed after the surgery for 3 or 14 days.Histological change of the obstructed kidney was observed by H-E staining.The protein expression and localization of transforming growth factor β1(TGF-β1) and a-smooth muscle actin(a-SMA) in renal tissues were detected with immunohistochemical staining.The mRNA levels of TGF-β1 anda-SMA were analyzed with reverse transcription-polymerase chain reaction.Results Compared with sham-operated group,UUO group exhibited severe renal interstitial fibrosis and expressions of TGF-β1 and a-SMA were markedly higher(P < 0.05),while renal interstitial fibrosis was less marked and levels of TGF-β1anda-SMA were down-regulated significantly in AcSDKP group(P < 0.05).Conclusions AcSDKP improves renal interstitial fibrosis by down-regulating TGF-β1 anda-SMA expression .更多还原