N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸抑制大鼠肾间质纤维化的研究

王明奡; 刘睿婵; 包宇实; 顾云鹤; 穆素红; 解汝娟

doi:10.3969/j.issn.1671-4091.2010.09.006

中国血液净化 >

2010 , Vol. 9 >Issue 9: 498 - 502

DOI: https://doi.org/10.3969/j.issn.1671-4091.2010.09.006

临床研究

N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸抑制大鼠肾间质纤维化的研究

王明奡 ,
刘睿婵 ,
包宇实 ,
顾云鹤 ,
穆素红 ,
解汝娟

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哈尔滨医科大学附属第一医院

收稿日期: 2010-01-07

修回日期: 1900-01-01

网络出版日期: 2010-09-12

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Study on the inhibition effect of the short peptide AcSDKP on renal interstitial fibrosis in rats

WANG Ming-ao ,
LIU Rui-chan ,
BAO Yu-shi ,
GU Yun-he ,
MU Su-hong ,
XIE Ru-juan

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1Department of Nephrology, 2Department of Pathology, The First Clinical Hospital Affiliated to Harbin Medical University, 150001, China

Received date: 2010-01-07

Revised date: 1900-01-01

Online published: 2010-09-12

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摘要

【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、14 d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 1(transforming growth factor- 1,TGF- 1)及崞交〖《鞍 ( -smooth muscle actin, -SMA)表达，RT-PCR方法检测TGF- 1及 -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- 1、 -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- 1及 -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。

关键词： N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸; 肾间质纤维化; 转化生长因子 1

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王明奡 , 刘睿婵 , 包宇实 , 顾云鹤 , 穆素红 , 解汝娟 . N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸抑制大鼠肾间质纤维化的研究[J]. 中国血液净化, 2010 , 9(9) : 498 -502 . DOI: 10.3969/j.issn.1671-4091.2010.09.006

Abstract

【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 -smooth muscle actin ( -SMA) in renal tissues were detected by immunohistochemistry. The mRNA levels of TGF-β1 and -SMA were measured by reverse transcription- polymerase chain reaction. Results Compared with sham-operated group, rats in UUO group exhibited severe renal interstitial fibrosis and higher expression of TGF-β1 and -SMA (P＜0.05), while those in UUO+AcSDKP group demonstrated less renal interstitial fibrosis, and lower expression levels of TGF-β1 and -SMA (P＜0.05). Conclusions AcSDKP treatment improves renal interstitial fibrosis in rats by down-regulating TGF-β1 and -SMA expression.

Key words： Renal interstitial fibrosis; Transforming growth factor β1

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