奇诺宁对低氧性肺动脉高压的治疗作用

Qi Nuoning in treatment of hypoxic pulmonary hypertension

目的探讨奇诺宁注射液对低氧性肺动脉高压（HPH）大鼠肺血管结构重建及肺血管形态学的影响。方法将36只健康雄性Wistar大鼠随机分为3组，每组12只。①对照组：室内空气正常饲养；②低氧组：在常压低氧舱内（氧浓度10．0％±0．5％），每日8h，连续30d；③治疗组：低氧条件同低氧组，自低氧第1天起每天给大鼠腹腔内注射1ml／kg奇诺宁注射液。对照组与低氧组每天腹腔内注射生理盐水量和治疗组相同。于低氧30d后分别用右心导管法测定肺动脉平均压（mPAP）、颈动脉平均压（mCAP），计算右心室肥大指数（RVHI），光镜下观察肺小动脉肌化程度，肺中、小肌型动脉相对中膜厚度（RMT）、相对中膜面积（RMA）的变化及肺血管形态学改变。结果①低氧组mPAP、RVHI较对照组明显升高（P〈0．01），治疗组较低氧组明显下降（P〈0．0t）。②低氧组肺组织中N0含量较对照组降低（P〈0．01），治疗组较低氧组升高（P〈0．01）。③低氧组肺中、小肌型动脉肌化程度、RMT、RMA较对照组明显增多（P〈0．05或P〈0．01），治疗组较低氧组肺中、小肌型动脉肌化程度、RMT、RMA减小，差异有统计学意义（P〈0．05或P〈0．01）。④mCAP三组之间比较差异无统计学意义。⑤Weigert弹力纤维染色切片显示，对照组大鼠肺小动脉内外弹力层完整，内外弹力层之间的厚度正常；低氧组大鼠肺小动脉内弹力纤维膜增厚，内外弹力层之间的距离明显增宽；治疗组大鼠肺小动脉内弹力纤维膜明显好转，内弹力层与外弹力层之间的距离增宽程度较低氧组减轻。结论慢性低氧可引起大鼠肺动脉内皮损伤、结构重建，导致肺动脉压上升，奇诺宁注射液可部分逆转肺血管结构重建，对HPH有良好治疗作用。

Objective To explore the influences of Qi Nuoning on pulmonary vascular remodeling and pulmonary vascular morphology in hypoxic pulmonary hypertension （HPH） rats. Methods 36 healthy male Wistar rats were randomly divided into three groups（ n = 12）. ①Control group： rats were breed indoor air.② Hypoxia group： rats were breed in ordinary pressure low chamber （oxygen concentration of 10.0%±0.5 %） for 30 days, 8 hours a day. ③Treated group ： rats were breed in ordinary pressure low chamber （oxygen concentration of 10.0 ± 0.5 %） and treated with 1 ml/kg Qi Nuoning by intraperitoneal injection,injected isodose physiological saline in control group and hypoxia group. After 30 days,we determined mean pulmonary arterial pressure （mPAP）, carotid artery mean pressure （mCAP） and right ventricuiar hypertrophy index （RVHI） by right heart catheterization. The museularization of pulmonary arterioles,relative medial thickness （RMT） and relative medial area （RMA） of pulmonary muscular artery, morphological changes of pulmonary vascular were observed under microscope. Results @mPAP and RVHI in hypoxia group increased remarkably compared with control group （ P 〈0.01）. MPAP and RVHI in treated group decreased remarkably compared with hypoxia group （ P 〈 0.01）. ② Nitric oxide （NO） content in the lung tissue in hypoxia group decreased remarkably compared with control group （P 〈 0.01）. NO content in the lung tissue in treated group rats increased remarkably compared with hypoxia group （ P 〈0.01）. ③Muscularization of pulmonary midium and small muscular arteries. RMT,RMA in hypoxia group increased remarkably compared with control group （ P 〈0.05 or P〈 0.01）. Muscularization of pulmonary arterioles, RMT, RMA in treated group decreased remarkably compared with hypoxia group （ P 〈0.05 or P 〈0.01）. ④There were no significant differences in mCAP among three groups （ P 〉 0.05）. ⑤ Weigert elastic fibers staining section showed that in pulmonary arterioles of rats internal and external elastic layer integrity and the thickness between the inside and outside of the elastic layer was normal in control group. Internal and external elastic layer was thickening and the distance between the inside and outside of the elastic layer was widen in hypoxia group. Compared with hypoxia group, in treated group pulmonary arterioles of rats remarkably released. Conclusions Chronic hypoxia can cause the rat pulmonary arteries endothelial injury, pulmonary vascular remodeling, resulting in pulmonary arterioles pressure rise. Pulmonary vascular remodeling and pulmonary vascular morphological changes can be partially reversed by Qi Nuoning. Qi Nuoning has good effects on HPH.