通心络对低压低氧肺动脉高压大鼠的保护作用及其NO机制

Protective Effect of Tongxinluo Pretreatment on Pulmonary Hypertension in Rats and Its NO Mechanism

目的:探讨通心络对低压低氧肺动脉高压大鼠的作用及其可能的NO作用机制。方法:30只健康雄性SD大鼠,随机分为随机分为低氧低压模型组(模型组)、低氧低压+通心络干预组(通心络干预组)、常氧常压对照组(对照组),每组10只,采用低压低氧舱,控制大气压50 Kp,浓度10%,模拟5000 m海拔的高原环境。模型组和通心络干预组大鼠平均每天入舱8 h,其余时间为常压常氧环境。通心络干预组每天入舱前给予通心络1.2 g生药/Kg灌胃1次,对照组在同一实验室的常压常氧环境中喂养。4周后取材,比较各组大鼠平均肺动脉压(m PAP),血管壁厚度百分比(WT%),小动脉平均血管壁面积与血管总面积的百分比(WA%)。硝酸还原酶法检测血清NO的含量,比色法检测血清e NOS、i NOS、T-NOS的含量,荧光定量PCR(RT-PCR)检测大鼠e NOS,i NOS的含量。结果:4周后,与对照组相比,模型组肺动脉WT%和WA%均高于对照组和通心络干预组(P<0.05)。模型组i NOS含量水平均高于对照组和通心络干预组(P<0.05)。模型组血清NO、e NOS含量及组织中e NOS的mRNA表达量均低于对照组和通心络干预组(P<0.05),差异具有统计学意义。结论:通心络对低压低氧肺动脉高压大鼠具有保护作用,该保护作用可能通过增加e NOS的含量,抑制i NOS的表达,从而增加NO净含量有关。

Objective：To investigate the protective effect of Tongxinluo pretreatment on pulmonary hypertension in rats and its possible NO mechanism. Methods ： Thirty male SD rats were randomly divided into 3 groups （ n = 10） ： control group ; model group and Tongxinluo pretreatment group. The control group used normal oxygen and normal pressure. The model group used low - pressure and low - oxygen and Tongxiuluo group was in low - pressure and low oxygen. The auto - modulating hyobaric and hypoxic cabin was used to simulate 5000 m high altitude environment. Tongxinluo pretreatment group animals were pretreated with Tongx- inluo[ 1.2 g/（ kg · d）] by orogastric route 4 weeks. The other two groups pretreatment was normal CMC -Na in the same. 4 weeks later, the mPAP, WT% and WA% were measured and the endothelial NOX （eNOS） ,inducible NOS （iNOS） activity and NO level were detected by ultraviolet spectrophotometer. The mRNA expression of myocardial eNOS and iNOS were detected by real - time fluorescence quantitative PCR （ RTFQ - PCR）. Results ： The WT% and WA% of model group were higher than the those of Tongxinluo group and control group. But compared with the model group, the Tongxinluo group＇s serum NO, eNOS levels and intestinal tissue eNOS mRNA expression elevated （P 〈 0. 05）, but the plasma iNOS of serum and lung iNOS mRNA expression decreased （P 〈0. 05 ）. Conclusion：Tongxingluo pretreatment has protective effects on pulmonary hypertension in rats. The mechanism may be related to inhibition of iNOS expression and increasing expression of eNOS, thereby increasing NO activity.