孟鲁司特对大鼠低氧性肺动脉高压的预防效应

Preventive Effects of Montelukast on Hypoxic Pulmonary Hypertension in Rats

目的 探讨半胱氨酸白三烯 ( Cys L T)在低氧性肺动脉高压发病中的作用和评价其受体拮抗剂孟鲁司特对低氧性肺动脉高压的预防效应。方法 将 3 0只雄性 Wistar大鼠分为对照组、低氧组和孟鲁司特预防组 ,以常压低氧复制肺动脉高压模型 ,采用酶免疫法检测大鼠血浆中白三烯 C4( L TC4)含量 ,对大鼠肺组织切片采用 HE染色 ,经图像分析技术测定大鼠肺小动脉管壁厚度的变化。结果 低氧组大鼠右心室肥厚指数〔 RV/( L V+ S)〕、肺小动脉管壁厚度指标〔管壁厚度占外径的百分比 ( WT% )和管壁面积占总面积的百分比 ( WA% )〕均高于正常对照组〔 RV/( L V+ S) :3 0 .85 %± 1.44 % vs2 0 .75 %± 1.97% ;WT% :2 3 .5 4%± 4.43 % vs13 .17%± 3 .67% ;WA% :72 .76%± 9.2 8% vs5 0 .41%± 6.3 7% ,P均 <0 .0 1〕,血浆中 L TC4浓度 ( 2 3 95 .40± 193 .86pg/m l)也高于正常对照组 ( 10 0 6.5 0± 193 .17pg/ml,P<0 .0 1) ;经孟鲁司特处理的低氧大鼠其 RV/( L V+ S)为 2 4.0 9%±1.0 9%、WT%为 15 .44 %± 4.72 %和 WA%为 5 1.98%± 12 .18%均低于低氧组 ( P<0 .0 1) ,而血浆中 L TC4浓度( 2 70 6.2 5± 3 5 0 .49pg/ml)与低氧组比较无显著性差异 ( P>0 .0 5 )。结论 低氧刺激血浆 L TC4的合成和释放 ,Cys L T参?

Objective To evaluate the role of cysteinyl leukotriene(CysLT) in the pathogenesis of hypoxic pulmonary hypertension and the preventive effects of montelukast, a CysLT receptor antagonist, on hypoxic pulmonary hypertension. Methods Thirty male Wistar rats were randomly divided into three groups: control group, hypoxic group and montelukast preventive group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for 3 weeks. The thickness of pulmonary arterioles was measured by a computerized image analyzer. The level of LTC 4 in plasma was measured by EIA. Results In the hypoxic group, the index of right ventricular hypertrophy〔RV/(LV+S)〕 and the index of wall thickness of pulmonary arteriole(WT% and WA%) increased significantly when compared against those in the control group〔RV/(LV+S):30.85%±1.44% vs 20.75%±1.97%; WT%: 23.54%±4.43% vs 13.17%±3 67%; WA%: 72.76%±9.28% vs 50.41%±6.37%, P<0.01, respectively〕. Meanwhile, the plasma level of LTC 4 in hypoxic rats was higher than that in control rats〔(2395.40±193.86) pg/ml vs (1006.50±193.17) pg/ml, P<0.01〕. In the preventive group, the RV/(LV+S)(24.09%±1.09%), WT% (15.44%±4.72%) and WA% (51.98%±12.18%) decreased remarkably as compared with those of the hypoxic group(P<0.01). The plasma level of LTC 4 in the preventive group (2706.25±350.49 pg/ml) was not significantly different from that in the hypoxic group(P>0.05). Conclusion Chronic hypoxia stimulates synthesis and release of LTC 4. CysLT may play an important role in the pathogenesis of hypoxic pulmonary hypertension and montelukast can prevent hypoxic pulmonary hypertension.