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

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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 effect of Tongxinluo on hypobaric hypoxic pulmonary hypertension in rats and its possible mechanism of NO. Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: model group, hypoxia and hypoxia + Tongxinluo intervention group (Tongxinluo intervention group), normobaric pressure control group Control group), 10 in each group. Low pressure hypoxia tank was used to control atmospheric pressure 50 Kp and concentration 10% to simulate altitude environment of 5000 m altitude. The rats in the model group and Tongxinluo intervention group were exposed to an average of 8 hours a day for the rest of the day. The rest time was atmospheric and normoxic conditions. The Tongxinluo intervention group was given Tongxinluo 1.2 g crude drug / Kg once daily before entering the capsule, and the control group was fed in the same laboratory under atmospheric and normoxic conditions. Four weeks later, the mean pulmonary artery pressure (m PAP), percentage of vessel wall thickness (WT%), mean arteriolar wall area and percentage of total vessel area (WA%) of rats in each group were compared. Nitric acid reductase method was used to detect the content of NO in serum. The contents of eNOS, iNOS and T-NOS in serum were detected by colorimetric assay. The content of eNOS and iNOS in rats were detected by real-time quantitative PCR (RT-PCR). Results: After 4 weeks, WT% and WA% of pulmonary artery in model group were significantly higher than those in control group and Tongxinluo intervention group (P <0.05). The level of iNOS in model group was higher than that in control group and Tongxinluo intervention group (P <0.05). The levels of NO, e NOS and eNOS mRNA expression in model group were lower than those in control group and Tongxinluo group (P <0.05), and the difference was statistically significant. Conclusion: Tongxinluo can protect rats from hypobaric hypoxia pulmonary hypertension. This protective effect may be related to increasing the content of eNOS, inhibiting the expression of iNOS and increasing the content of NO.
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