摘要
目的观察钙调神经磷酸酶(CaN)在醛固酮(Ald)诱导的心肌肥大信号转导机制中的作用及其调节。方法24只Wistar大鼠随机分为2组:实验组和对照组。实验组给予醛固酮腹腔注射后,再随机分为3组,分别给予环孢霉素A、螺内酯、及生理盐水干预,对照组仅腹腔注射生理盐水。测定大鼠血浆中血管活性因子Ald、AngⅡ、ET1与NO-3的浓度,心重/体重,心肌组织中的CaN活性;心肌组织中肥大相关基因心房利钠因子(ANF)及CaNAβmRNA的水平,同时用免疫组化方法观察心肌胞浆中CaN的表达。结果醛固酮腹腔注射后血浆中的醛固酮水平明显增高,醛固酮腹腔注射4周可使心肌肥大相关基因ANFmRNA水平明显升高,心肌中CaN活性明显升高,心肌细胞浆中的CaN表达上调;环孢霉素A及螺内酯干预4周,可明显抑制心肌CaN活性,并下调ANF(P<0.05)的表达。结论CaN参与了外源性醛固酮诱导的心肌肥大的信号通路,醛固酮通过活化CaN,使肥大相关基因表达增加产生心肌肥大。螺内酯通过拮抗醛固酮与受体结合抑制心肌肥大。
Objective To investigate the role and its regulation of calcineurin-dependent signal transduction on cardiac hypertrophy induced by aldosterone (Ald) in rats. Methods Twenty-four Wistar rats were randomly divided into experimental group and control group. Experimental group was treated with aldosterone (ip) and then divided into three subgroups randomly. They were treated with CsA(5 mg/kg·d), spironolactone(18 μg/d), and normal saline for 4 weeks. Control group received normal saline(ip). The concentrations of plasma aldosterone, angiotensin Ⅱ (Ang Ⅱ), endothelins(ET-1) , nitrogen monoxide(NO+- 3)and LW/BW , as well as the activity of CaN in cardiac tissue were measured. Half quantitative PCR was employed to determine the levels of ANF and CaNAβ mRNA in cardiac tissue. The expression of CaN in cardiac tissue were examined by immunohistochemical staining. Results The plasma concentration of aldosterone was increased obviously in expermental groups. Aldosterone increased the gene expression of ANF and CaNAβ mRNA in myocardium as well as the activity of CaN. The higher expression of CaN in cardiac tissue was also shown. Spironolactone and cyclosporine A (CsA) treatment significantly inhibited the activities of CaN in myocardium and down regulated the expression of ANF gene. Conclusion These results suggest that CaN plays an important role in the signal pathway of cardiac hypertrophy induced by exogenous aldosterone. Aldosterone actives CaN in cardiac tissue and the genes related to cardiac hypertrophy.=
出处
《高血压杂志》
CSCD
北大核心
2005年第7期432-436,共5页
Chinese Journal of Hypertension
基金
本课题受"十五"军队医药卫生科研基金重点课题资助(02Z0010)
