川芎嗪对肺动脉高压大鼠肺血管凋亡的影响

Effect of ligustrazine （川芎嗪 ） on pulmonary arteria apoptosis in pulmonary hypertension

目的观察川芎嗪对低O2高CO2肺动脉高压大鼠肺动脉平滑肌凋亡以及Bcl一2、Bax表达的影响。方法将30只SD大鼠按随机数字表法分为正常对照组（N组）、低O2高CO2组（H组）、低O2高CO2＋川芎嗪组（H＋LTZ组）3组，每组10只。监测各组大鼠血流动力学变化；观察肺细小动脉管壁面积与总面积比值（wA／TA）；用原位末端缺刻标记法（TuNEL）检测肺细小动脉凋亡情况，并计算凋亡指数（AI）；用免疫组化法检测Bcl-2、Bax的含量。结果H组和H＋LTZ组平均肺动脉压（mPAP）、右心室重量比、WA／TA比值均明显高于N组，H＋LTZ组则均明显低于H组（P均〈0．01）；3组间平均颈动脉压（mCAP）无明显差异（P均〉0．05）。H组和H＋LTZ组肺细小动脉AI显著低于N组，H＋LTZ组则显著高于H组（P〈0．05或P〈0．01）。H组和H＋LTZ组Bcl一2含量均显著高于N组，Bax含量、Bax／Bcl一2比值均显著低于N组；H＋LTZ组Bcl—2含量显著低于H组，Bax含量、Bax／Bcl一2比值显著高于H组（P均〈0．01）。结论川芎嗪有抑制慢性低Oz高C0。肺动脉高压和肺血管重建的作用，抑制肺细小动脉的增殖、促进肺细小动脉凋亡是其可能机制。

Objective To investigate the effect of ligustrazine （川芎嗪） on smooth muscle apoptosis of pulmonary arteriole and the expressions of Bcl-2 and Bax in rats with pulmonary arterial hypertension induced by hypoxic hypercapnia. Methods Thirty Sprague-Dawley （SD） rats were randomly divided into three groups： normal control group （N）, hypoxic hypereapnie group （H）, and hypoxic hypereapnie＋ligustrazine group [（H＋LTZ）, each n = 103. The changes of hemodynamies of rats were monitored; under light microscope, the ratio of vessel wall area and total area （WA/TA） of pulmonary arterioles in the three groups were measured. The apoptosis of pulmonary arterioles was tested with terminal deoxynueleotidyl transferase mediated dUTP-biotin nick end labeling （TUNEL） and the apoptosis index （AI） was calculated. Immunohistochemistry was applied to determine the contents of Bel-2 and Bax in cytoplasm. Results The level of mean pulmonary arterial pressure （mPAP）, right ventriele/（left＋interventrieular septum） ratio and the ratio of vessel WA/TA were significantly higher in H group and H＋LTZ group than those in N group, and values were obviously lower in H＋LTZ group than those in H group （all P〈0.01）. The mean carotid arterial pressure （mCAP） of the three groups had no significant differences （all P〉0. 05）. The apoptosis indexes （AI） of pulmonary arteriole in H and H＋LTZ groups were markedly lower than that in N group, and the AI of pulmonary arteriole of H＋LTZ group was obviously higher than that in H group （P〈0. 05 or P〈 0. 01）. In H and H＋LTZ groups, the content of Bel-2 was significantly higher, the content of Bax and Bax/ Bcl-2 ratio was obviously lower than that in N group. In H＋LTZ group, the content of Bel-2 was markedly lower and the content of Bax and Bax/Bel-2 ratio was significantly higher than that in H group （all P〈0.01）. Conclusion Ligustrazine can lower chronic pulmonary arterial hypertension induced by hypoxie hypercapnia and inhibit structural remodeling of pulmonary arteries. The inhibition of pulmonary arteriole proliferation and promotion of its apoptosis may play a role in the mechanism.