病毒性心肌炎小鼠凋亡基因表达及卡维地洛的干预作用

Effect of carvedilol on expression of apoptosis - related genes in mice with acute viral myocarditis

目的探讨新型B受体阻滞剂卡维地洛对病毒性心肌炎（VMC）小鼠Bcl-2／Bax凋亡基因表达的影响。方法4周龄Balb／c雄性小鼠随机分为心肌炎组、卡维地洛治疗组（卡维地洛组）和对照组。心肌炎组和卡维地洛组经腹腔接种柯萨奇病毒B3（CVB3）诱发急性VMC，对照组接种不含病毒的RPMll640培养基。卡维地洛组于接种病毒次日开始灌服卡维地洛5mg／kg，每132次；心肌炎组和对照组灌服生理盐水。于接种后的第7、14天小鼠取血后处死，留取心脏标本，苏木精-伊红染色检测心肌病理积分、逆转录聚合酶链式反应（RT—PCR）技术检测Bcl-2mRNA和BaxmRNA表达。结果心肌炎组心肌组织病理积分较对照组增高（P〈0．01），卡维地洛组较心肌炎组病理积分降低（P〈0．05）；与对照组比较，心肌炎组Bcl-2mRNA和BaxmRNA表达均增高（P〈0．01），Bcl-2mRNA／BaxmRNA比值降低；与心肌炎组比较，卡维地洛组Bcl-2mRNA表达增高、BaxmRNA表达降低，Bcl-2mRN／BaxmRNA比值增高（均为P〈0．01）。结论CVB性心肌炎心肌病理损害与凋亡基因Bcl-2／Bax表达异常有关，卡维地洛能够通过抑制Bax基因、增强Bcl-2基因表汰减轻心脏损害。

Objective To investigate the effect of carvedilol on expression of Bcl - 2 and Bax in mice with acute viral myocarditis which was induced by coxsackie virus B3 virus （ CVB3 ）. Methods BALB/C mice were randomly divided into three groups ： the viral myocarditis （ VMC ） group, the earvedilol - treated group, and control group. The first two groups were intraperitoneally inoculated with CVB3 to induce myocarditis, control group with virus -free PPMI 1640 medium instead. Carvedilol was orally administered 5 mg · kg^-1 , twice a day in carvedilol group from the next day after injecting virus. Control group and VMC group were orally administered normal saline instead. The mice were killed on days 7 and 14 respectively. Polymerase chain reaction were performed to evaluate the activation of the expression of Bcl - 2 mRNA/Bax mRNA in myocardial tissue. Results The pathological score was significantly higher in VMC group than in control group （P 〈 0.01 ） , and was decreased significantly in carvedilol- treated group compared with that of the VMC group （ P 〈 0.05 ）. Compared with control group, the expression levels of both Bcl - 2 mRNA and Bax mRNA in the VMC group were significantly increased （P 〈 0.01 ）, but the ratio of Bcl - 2 mRNA/Bax mRNA was significantly lower （P 〈0.01）. In carvedilol -treated group the expression level of Bcl -2 mRNA were significantly upregulated （P 〈 0. O1 ）, Bax mRNA significantly downregulated （ P 〈 0.01 ） and the ratio of Bcl - 2 mRNA/Bax mRNA was significantly increased compared with VMC group （ P 〈 0.01 ）. Conclusion Carvedilol protects against viral myocarditis by downreg- ulating the expression of Bcl -2 mRNA, and upregulating Bax mRNA.