二氯乙酸盐对野百合碱诱导大鼠肺动脉高压作用的影响

目的 探讨二氯乙酸盐(DCA)对野百合碱(MCT)诱导大鼠的肺动脉高压中肺血管平滑肌细胞增殖及凋亡的影响.方法 将雄性SD大鼠随机分为3组:正常组,模型组和治疗组,每组各10只.后两组用野百合碱一次性皮下注射以诱导肺动脉高压产生.于注射MCT 7 d后,治疗组予以DCA喂养,正常组和模型组予以等量的生理盐水喂养,各组分别于第7、14、21、28天进行肺动脉平均压力测量.28 d后处死动物,取肺组织进行常规病理染色和反映细胞增殖及凋亡的免疫组织化学染色.结果 与模型组相比,治疗组的平均肺动脉压从第14天起开始降低,到第28天时已是模型组的一半(P<0.05).28 d后,治疗组的肺动脉中膜厚度百分比和右心室肥厚指数均比模型组显著降低(均P<0.05).与模型组相比,治疗组的增殖细胞核抗原(PCNA)增殖度降低(P<0.05),而Caspase-3阳性率升高(P<0.05).结论 DCA可以抑制肺动脉平滑肌细胞增殖并促进其凋亡,从而逆转肺血管重构.

Effect of Dichloroacetate on Monocrotaline-induced Pulmonary Hypertension in Rats

Objective To discuss the effect of Dichloroacetate(DCA) on proliferation and apoptosis of pulmonary arterial smooth muscle cells(PASMCs) in Monocrotaline-induced pulmonary arterial hypertension(PAH).Methods Male SD rats were randomly divided into 3 groups:control,model and DCA groups(n=10 in each group).In the model and DCA groups,the rats were subjected to single subcutaneous injection of MCT to induce the PAH.DCA was given to DCA group at day 7.At the same time,the equivalent volume of isotonic NaCl was given to the other groups.The mean pulmonary arterial pressure(mPAP) of each group was measured on day 7,14,21 and 28.On day 28,the lung tissue was subjected to HE staining and immunohistochemistry staining.The expression of proliferating cell nuclear antigen(PCNA) and Caspase-3 was detected in PASMCs.Results Compared with the model group,the mPAP in DCA group was decreased from day 14,which was almost half of the model group on day 28(P<0.05).Meanwhile,the media tunica thickness percentage and the right ventricular hypertrophy index in DCA group was reduced significantly(P<0.05).PCNA expression level in DCA group was lower than in model group,while Caspase-3 in DCA group significantly higher(P<0.05).Conclusion DCA can reverse pulmonary vascular remodeling through anti-proliferation and pro-apoptosis.