缬沙坦对高血压大鼠心肌组织CX43表达的抑制作用

Inhibition Effect of Valsartan on the Expression of CX43 in Myocardium of Hypertensive Rat

目的:探讨高血压大鼠心肌组织缝隙连接蛋白43(CX43)的表达,应用缬沙坦干预,研究其可能机制。方法:32只健康雄性SD大鼠随机分为空白对照组(n=8)、假手术组(n=8)以及模型组(n=16),模型组以二肾一夹方法建立,模型建立成功后,随机分为缬沙坦治疗组(n=8)和模型对照组(n=8)。治疗组给予缬沙坦按照30mg/(kg·d)剂量灌胃,空白对照组、假手术组以及模型对照组分别给予相同体积的生理盐水灌胃,每日一次。给药8周后,彩色多普勒超声检测心功能,麻醉处死动物,SP免疫组化法检测心肌组织中胰岛素样生长因子(IGF)-1、CX43及NF-κB的表达。结果:与空白对照组相比,假手术组IGF-1蛋白表达率、CX43及NF-κB表达变化不明显,心功能无明显变化,模型组则明显升高(P<0.05),心功能减弱(P<0.05);与模型对照组相比,缬沙坦治疗组上述指标则改善明显(P<0.05)。结论:肾血管性高血压大鼠心功能降低明显,与此同时IGF-1、CX43蛋白及NF-κB表达均显著增高,应用缬沙坦治疗8周后,上述指标均降低明显,同时心功能有明显改善,提示缬沙坦可通过降低IGF-1表达、抑制CX43表达改善心功能,NF-κB可能参与了这一过程。

Objective：To explore the expression of CX43 in the cardiac tissues of two-kidney-one-clip（2K1C）renal vascular hypertensive rats,and approach the protective effect of valsartan in this process.Methods：32healthy male SD rats were randomly divided into three groups,8as normal control group,8as sham operation group,16 as operation modeling,which were induced that respectively in by the classic methods of 2K1 C.After the success of modeling,then they were divided into hypertension control group and valsartan treat group,each contains 8.The drug was dissolved in sodium chloride and administrated by gavage for eight weeks,valsartan 30 mg/kg once a day,the other three groups were administrated the same volume sodium chloride.Eight weeks later,heart function was detected by Doppler echocardiography,all rats were anesthetized to death,SP immunohistochemical staining was used respectively to detect the expression of IGF-1,CX43 and NF-κB.Results：Compared with that respectively in the normal control group,blood pressure,the expression of IGF-1,protein CX43 and NF-κB increased significantly in the hypertension models（P〈0.05）,while these indices in the cardiac function decreased significantly（P〈0.05）,the sham operation group has no difference;Compared with the hypertension models,the valsartan treated group improved significantly（P〈0.05）.Conclusion：In the two-kidney-one-clip renal vascular hypertensive rats,the expression of IGF-1,the protein of CX43 and NF-κB increased significantly.After valsartan was used,the above all were improved,which showed that through the ways of decreasing the expression of IGF-1and CX43,valsartan could improve the cardiac function,and NF-κB might be involved in this process.