野百合碱诱导孕鼠肺动脉高压机制与其对子代大鼠的影响

Mechanism of monocrotaline induced pulmonary hypertension in pregnant rats and its effect on offspring rats

目的探讨野百合碱(monocrotaline,MCT)诱导孕鼠发生肺高压(pulmonary hypertension,PH)的作用机制及其对子代大鼠的影响。方法将12只孕期大鼠随机分成MCT组与对照组,MCT组皮下注射MCT(60 mg·kg^(-1)),对照组皮下注射生理盐水(60 mg·kg^(-1)),42 d后检测MCT对孕鼠的影响,77 d后检测MCT对8周子代大鼠的影响。Western blot检测线粒体融合蛋白MFN-2表达。结果MCT组孕鼠相比于正常组除体质量无明显变化外,右心室收缩压、右心室与胫骨长度的比值,以及右心室与左心室+室间隔和的比值均显著增加,HE染色结果显示肺血管明显增厚。MCT组子代大鼠的上述指标均无显著变化。Western blot结果显示,MCT组孕鼠肺血管的线粒体融合蛋白2(mitofusin 2,MFN-2)表达相较于正常组明显下降,而MCT组子代大鼠相比正常组无明显变化。结论MCT可诱导孕期大鼠发生PH,肺血管重构,其机制可能与肺血管中MFN-2的表达降低相关。MCT诱导后孕期大鼠的子代大鼠未出现上述变化,表明MCT的代谢毒性不包括诱导子代大鼠发生PH。

Objective To investigate the mechanism of monocrotaline(MCT)induced pulmonary hypertension(PH)in pregnant rats and its effect on offspring rats.Methods Twelve pregnant rats were randomly divided into MCT group and control group.MCT group was injected subcutaneously with MCT(60 mg·kg^(-1))and control group was injected subcutaneously with normal saline(60 mg·kg^(-1)).Then observed the effects of MCT on pregnant rats after 42 d and the effects of MCT on 8-week offspring rats after 77 d.Finally,the expression condition of MFN-2 was measured by Western Blot.Results Compared with the control group,the pregnant rats in the MCT group had no significant changes on body weight,but RV(right ventricle)∶TL(tibial length),RV∶[LV(left ventricle)+S(septum)]and RVSP(right ventricular systolic pressure)were obviously increased.HE staining showed that the pulmonary vessel was thickened.The above index had no significant changes in offspring rats of the MCT group.Results of Western Blot showed that compared with the control group,the expression of mitofusin 2(MFN-2)in the pulmonary vessels of MCT group pregnant rats was decreased while the offspring of the MCT group didn′t show significant changes.Conclusion MCT can induce pulmonary vascular remodeling and PH in pregnant rats,which may be related to the low expression of MFN-2 in pulmonary vessels.The changes do not occur in the offspring of pregnant rats after MCT induction,indicating that the metabolic toxicity of MCT does not include the induction of PH in offspring rats.