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二氯乙酸盐对肺高压血管重构作用机制的研究

The mechanism of the effect of dichloroacetate on pulmonary hypertension with pulmonary vascular remodeling

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【作者】 张敏修宗谊

【Author】 ZHANG Min;XIU Zong-yi;Department of Cardiac Surgery,the First Affiliated Hospital of China Medical University;

【机构】 中国医科大学附属第一医院心脏外科

【摘要】 目的 观察二氯乙酸盐(DCA)对野百合碱(MCT)诱导的肺高压大鼠肺小动脉重构的作用,以及对bcl-2、bax表达的影响。方法 大鼠60只随机分为三组:对照组、模型组及治疗组。模型组及治疗组皮下注射MCT建立肺动脉高压模型,对照组注射等量溶剂。7 d后治疗组以80 mg·kg-1·d-1DCA溶液喂养,对照组和模型组饮用水喂养。各组于第7、14、21、28天随机选3只大鼠行平均肺动脉压力测量。28 d后处死所有大鼠,取心脏及肺进行检测。结果 平均肺动脉压力测量:建模第14天始,治疗组低于模型组;中膜厚度百分比:模型组大于治疗组大于对照组;右心室肥厚指数:模型组大于治疗组大于对照组;bcl-2染色阳性率:模型组高于治疗组高于对照组;bax染色阳性率:治疗组高于模型组高于对照组;TUNEL.染色阳性率:治疗组大于对照组大于模型组,以上差异均有统计学意义(P<0.05)。结论 DCA在抑制bcl-2表达的同时使bax的表达增强,从而抑制肺动脉平滑肌细胞增殖并促进其凋亡,逆转肺血管重构。

【Abstract】 Objective To investigate the effect of Dichloroacetate(DCA) on the reconstruction of pulmonary artery and the expression of bcl-2 and bax protein of pulmonary hypertension rats which established by Monoerotaline(MCT).Methods The rats were divided into three groups randomlyicontrol group,model group and DCA group.In the model group and DCA group,he rats were subjected to injection of MCT to induce the pulmonary arterial hypertension.while the control group was subjected to subcutaneous injection of solvent.DCA was given to DCA group form day 7.At the same time,the equivalent volume of normal drinking water was given to the other two groups.The mean pulmonary arterial pressure was measured on three rats which were randomly selected in each group on day 7,14,21 and 28.Then the rest of rats were sacrificed after28 days,and after that all heart and lung tissues were detested.Results The mPAP of DCA group was higher than control group and lower than model group(P<0.05).Meanwhile,The mPAP of model group was higher than control group(P<0.05).Compared with the model group,the mPAP of DCA group had decreased from day 14.Compared with the model group,the media tunica thickness percentage and the right ventricular hypertrophy index(RVHl)of DCA group reduced significandy(P<0.05).Bcl-2-positive cells of model group was much higher than DCA group and control group(P<0.05),however,bax-positive cells of model group was much lower than DCA group but higher than control group(P<0.05).TUNEL-positive cells of DCA group were high than the other two groups(P<0.05).Conclusion DCA inhibit the proliferation andpromote the apoptosis of smooth muscle cell in pulmonary artery by inhibiting the express of bcl-2 and enhancing the expressiong of bax,and thus maybe reverse the reconstruction of pulmonary artery.

  • 【文献出处】 中国心血管病研究 ,Chinese Journal of Cardiovascular Research , 编辑部邮箱 ,2013年10期
  • 【分类号】R543.2
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