摘要
目的研究血管紧张素转化酶抑制剂(ACEI)依那普利对单侧输尿管梗阻大鼠肾组织骨成形蛋白-7(BMP-7)及其受体BMPR-Ⅱ、ALK-2、ALK-3、ALK-6表达的影响。方法采用单侧输尿管梗阻(UUO)大鼠模型,治疗组于造模前24h-造模后7d以依那普利10mg/(kg.d)灌胃,另设假手术组为正常对照,造模7天后,应用免疫组织化学法观察肾脏BMP-7、TGF-β1蛋白表达,半定量RT-PCR法检测肾脏BMP-7及其受体BMPR-Ⅱ、ALK-2、ALK-3、ALK-6mRNA表达水平。结果与假手术对照组相比,UUO大鼠肾脏BMP-7及其受体BMPR-Ⅱ、ALK-2和ALK-3mRNA表达明显减少,TGF-β1蛋白表达明显增高,而给予依那普利治疗后能够显著上调BMP-7及其受体BMPR-Ⅱ、ALK-2和ALK-3的表达,下调TGF-β1的表达,减轻肾间质纤维化。结论依那普利可显著上调BMP-7及其受体表达,减轻梗阻肾间质纤维化,这一作用可能与抑制TGF-β1的致纤维化活性有关。
[Objective] To investigate the effects of ACEI enalapril on the expression of BMP-7 and its receptors（BMPR-Ⅱ,ALK-2,ALK-3,ALK-6）in the kidney after unilateral ureteral obstruction of rats.[Methods] The UUO models were induced by ligating the left ureter.Rats were divided into sham operation,model and treatment groups（enalapril 10 mg/kg·d by gastric gavage from 24 hours before the obstruction to the 7th day after the obstruction）.Rats were sacrificed at the 7th day after UUO was initiated.The protein expression site and level of BMP-7 and TGF-β1 was detected by immunohistochemiccal staining.The mRNA level of BMP-7,BMPR-Ⅱ,ALK-2,ALK-3 and ALK-6 was examined by RT-PCR.[Results] Compared to sham operation groups,the renal protein expression of BMP-7 and the renal mRNA levels of BMP-7,BMPR-Ⅱ,ALK-2 and ALK-3 were significantly decreased,but the renal protein expression of TGF-β1 increased and the renal mRNA level of ALK-6 did not change in UUO rats.Blockade of AnⅡ with enalapril significantly increased the expression of BMP-7 and its receptors（BMPR-Ⅱ,ALK-2,ALK-3）.Similarly the inhibition of AnⅡ resulted in obvious suppression of TGF-β1 expression in obstructed kidney.However,enalapril showed no evident effect on the mRNA expression of ALK-6.[Conclusion] Enalapril significantly increases the expression of BMP-7 and its receptors and suppresses the expression of TGF-β1 in obstructed kidneys,which may partly relate to the effect mechanism of enalapril.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2007年第14期1693-1696,1700,共5页
China Journal of Modern Medicine
