B型钠尿肽在大鼠心肌纤维化中的变化及卡维地洛的干预作用

Change of B Type Natriuretic Peptide in Myocardial Fibrosis in Rats and Effects of Carvedilol

目的研究异丙基肾上腺素(ISO)诱导的大鼠心肌纤维化过程中血清B型钠尿肽(BNP)和心肌BNP mRNA表达变化的意义,以及β-受体阻断剂卡维地洛的干预作用。方法将46只SD大鼠随机分为4周模型组(n=10)、8周模型组(n=9)、卡维地洛组(n=11)、4周对照组(n=8)和8周对照组(n=8)。模型组及卡维地洛组大鼠给予皮下注射ISO 10mg.kg-1.d-1,两个对照组给予皮下注射等量0.9%氯化钠溶液,共7d,至4周时,将4周模型组和4周对照组大鼠处死,同时卡维地洛组开始给予卡维地洛10mg.kg-1.d-1灌胃,8周模型组和8周对照组给予等量蒸馏水灌胃,共4周,至第8周末处死剩余大鼠,各组大鼠均测心重指数(HWI),MASSON染色后测心肌胶原积分(CVF),ELISA法检测血清中BNP水平,RT-PCR法检测心肌BNP的mRNA表达。结果 4周模型组HWI、CVF、血清BNP水平及心肌BNP mRNA表达较4周对照组升高,差异有统计学意义(P<0.01);8周模型组较4周模型组上述指标均升高,差异有统计学意义(P<0.01)。血清BNP与心肌BNP mRNA表达呈正相关(r=0.647,P<0.01)。卡维地洛组与8周模型组比较,上述指标水平均下降,差异有统计学意义(P<0.01)。结论 BNP可作为心肌纤维化早期诊断和严重程度的指标,卡维地洛可以有效改善心肌纤维化严重程度,降低血清BNP水平,使BNP的表达量降低。

Objective To examind serum B-type natriuretic peptide（BNP） levels and BNP-mRNA expression in the ventricular myocardium tissue of ispproterenol（ISO）-induced myocardial fibrosis（MF） rats and the effects of β-adrenergic receptor blocker carvedilol.Methods Forty Sprague-Dawley rats were randomly assigned to 5 groups： MF1,MF2,carvedilol-treated MF,contiol 1 and control 2.Cardiac fibrosis models were induced in MF1、MF2 and carvedilol-treated group by subcutaneous injection of ISO（10 mg.kg-1.d-1for 7 days）.Rats of control 1 and control 2 were injected normal saline instead.After 4 weeks,the rats of the MF1 and the control 1 groups were sacrificed,the carvedilol-treated group were administered carvedilol（10 mg.kg-1.d-1for 4 weeks） through direct gastric gavage,the MF2 and the control 2 groups were given equal distilled water instead.The rats were sacrificed 4 weeks after carvedilol or distilled water administration.All the rats were were measured serum BNP levels using ELISA,BNP mRNA expression of the ventricular myocardium by RT-PCR,the collagen volume fraction（CVF） after MASSON staining,and the heart weight index（HWI）.Results The HWI,the CVF,erum BNP levels and BNP mRNA expression in the ventricular myocardium were significantly higher in the MF1 group than those in the control 1 group（P 0.01）,and in the MF2 group than those in the MF1 group,the difference was statistically significant（P 0.01）.There were positive correlations between serum BNP levels and myovardial BNP mRNA expression in the MF group（r =0.647,P 0.01）.The heart weight index、the collagen volume fraction、serum BNP levels and BNP mRNA expression in the carvedilol-treated group were reduced compared with the MF2 group,the difference was statistically significant（P 0.01）.Conclusion BNP can be used as early diagnosis and severity index in myocardial fibrosis.Carvedilol can effectively reduce myocardial fibrosis severity and the serum BNP level and the expression of ventricular myocardium BNP.