大黄酸对慢性移植肾肾病大鼠肾组织抗纤维化因子表达的影响

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (10): 1114-1120.

大黄酸对慢性移植肾肾病大鼠肾组织抗纤维化因子表达的影响

苏健¹, 殷立平¹, 张鑫¹, 李必波¹, 刘丽², 李惠³

¹南京中医药大学附属江苏省中医院泌尿外科,²中心实验室,³病理科,南京 210029,江苏

收稿日期:2011-07-15 修回日期:2011-09-28 出版日期:2011-10-26 发布日期:2011-11-02
作者简介:苏健,男,博士,主治医师,研究方向:泌尿外科临床。Tel: 13182817113, E-mail: nn77315@sohu.com

Influence of rhein intervention on the expression of HGF and BMP7 in renal tissue of rats with chronical allograft nephropathy

SU Jian¹, YIN Li-ping¹, ZHANG Xin¹, LI Bi-bo¹, LIU Li², LI Hui³

¹Department of Urology, ²Centre Laboratory, ³Department of Pathology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu, China

Received:2011-07-15 Revised:2011-09-28 Online:2011-10-26 Published:2011-11-02

摘要/Abstract

摘要： 目的: 观察慢性移植肾肾病(CAN)大鼠肾组织中肝细胞生长因子(HGF)、骨形态发生蛋白(BMP7)的表达及大黄酸对其影响。方法: 以F344及Lewis大鼠分别作为供受体,建立CAN大鼠动物模型。将移植后30只大鼠分为治疗组(n=16)及模型组(n=14),另以5只Lewis正常大鼠作为对照组。治疗组予以大黄酸 100 mg·kg^-1·d^-1 灌胃,模型组及对照组给予等量的 0.5％羧甲基纤维素钠溶液。于移植后1个月、2个月及4个月分别收集大鼠的血和尿样,检测肾功能及尿蛋白含量。并于移植后2个月及4个月分别宰杀大鼠,观察各组大鼠移植肾组织病理学变化。并应用免疫组化以及实时荧光定量PCR方法分别检测CAN大鼠肾组织HGF、BMP7以及转化生长因子β₁(TGF-β₁)的蛋白质表达水平以及mRNA表达水平。结果: (1)与模型组比较,大黄酸治疗组大鼠肾功能改善(P<0.05 );肾组织病理检查示肾间质纤维化及间质炎症明显改善(P<0.05 );(2)与模型组比较,大黄酸治疗组大鼠肾组织TGF-β₁无明显差异,但抗纤维化因子BMP7及HGF明显升高(P<0.05 )。结论: (1)大黄酸能改善CAN大鼠肾功能及肾脏慢性病变;(2)大黄酸有可能通过诱导肾组织抗纤维化因子HGF、BMP7表达,抑制肾组织炎细胞浸润,发挥抗肾组织纤维化的作用,从而延缓CAN的进展。

关键词: 大黄酸, 慢性移植肾肾病, 肾间质纤维化, 机制

Abstract: AIM: To investigate the expression of HGF and BMP7 in renal tissue of rats with chronical allograft nephropathy (CAN) and the influence of rhein intervention on their expression. METHODS: We used Fisher rats as donors and Lewis rats as recipients to establish the model of chronic allograft nephropathy. 30 rats with transplanting kidneys were randomly divided into two groups: 16 rats in blank group and 14 rats in rhein intervention group. 5 normal lewis rats were as controls. The intervention group was given rhein oral solution 100 mg·kg^-1·d^-1 by gavage after transplantation. The blank group and control group were given 0.5% solution of sodium carboxymethyl cellulose. The blood and urine sample were collected at 4 weeks, 8 weeks and 16 weeks after transplantation respectively and renal function and total urine protein were examined. Half of rats in each group were killed at 8 weeks and 16 weeks for examining the renal pathology. And then we used immunohistochemical methods and real-time quantitative PCR to detect the protein expression levels and mRNA expression levels of HGF, BMP7 and transforming growth factor β₁(TGF-β₁) in CAN rats kidney tissues. RESULTS: (1) The rhein intervention group was significantly different from blank group(P<0.05 ). Rhein can improve renal functions and significantly reduce the grade of renal fibrosis and interstitial inflammation(P<0.05 ); (2) The levels of BMP7 and HGF were markedly elevated in renal tissues of rhein intervention group(P<0.05 ). However, the expression of TGF-β₁ was similar between these two groups. CONCLUSION: Rhein can improve renal functions and reduce the grade of renal fibrosis and interstitial inflammation, which may associate with that rhein plays a role in anti-inflammation, inducing the expression of BMP7 and HGF.

Key words: Rhein, Chronical allograft nephropathy, Renal fibrosis, Mechanism

中图分类号:

R965.2

苏健, 殷立平, 张鑫, 李必波, 刘丽, 李惠. 大黄酸对慢性移植肾肾病大鼠肾组织抗纤维化因子表达的影响[J]. 中国临床药理学与治疗学, 2011, 16(10): 1114-1120.

SU Jian, YIN Li-ping, ZHANG Xin, LI Bi-bo, LIU Li, LI Hui. Influence of rhein intervention on the expression of HGF and BMP7 in renal tissue of rats with chronical allograft nephropathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(10): 1114-1120.

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