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100mg.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。
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(P0.05).Rhein can improve renal functions and significantly reduce the grade of renal fibrosis and interstitial inflammation(P0.05);(2) The levels of BMP7 and HGF were markedly elevated in renal tissues of rhein intervention group(P0.05).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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2011年第10期1114-1120,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics