二氮嗪防治低氧性肺动脉高压作用机制.docVIP

二氮嗪防治低氧性肺动脉高压作用机制 　 作者：李少民　成少利　万俊哲　裴斐　周斌 【摘要】 　　目的 探讨二氮嗪阻断低氧性肺动脉高压形成的机制，为临床治疗肺动脉高压提供理论和实验依据。方法 将SD大鼠随机分为三组：肺动脉高压组(PH)、二氮嗪阻断组(DB)和正常对照组(N)。肺动脉高压组和二氮嗪阻断组在常压低氧舱饲养20d，第10天起二氮嗪阻断组每天缺氧前半小时使用二氮嗪，按50mg/kg腹腔注射，每日1次，共10次，肺动脉高压组每天注射生理盐水3mL/kg；正常对照组：10只，常规饲养大鼠。采用组织学方法和天狼星红染色结合偏振光显微镜对照观察肺动脉高压组、二氮嗪阻断组低氧性肺动脉高压肺血管壁厚度、管腔大小以及Ⅰ、Ⅲ型胶原蛋白含量的变化。结果 肺动脉高压组大鼠肺血管壁厚度增加，管腔狭窄，肺间质Ⅰ、Ⅲ型胶原蛋白含量显著高于二氮嗪阻断组。结论 二氮嗪可以对抗由缺氧所致的肺间质纤维化和肺血管重建。 【关键词】 低氧性肺动脉高压；二氮嗪；胶原蛋白；发病机制 　　Effects of diazoxide on hypoxia pulmonary artery hypertension 　　ABSTRACT: Objective To provide the theoretical basis and experimental foundation for the clinical research and treatment of hypoxia pulmonary artery hypertension through investigating the mechanism of diazoxide on hypoxia pulmonary artery hypertension. Methods The rats were divided into three groups: the rats in the pulmonary hypertension group (PHG) and diazoxide blockage group (DBG) were kept in low oxygen cabin for 20 days. From the tenth day, the diazoxide blockage group was given intraperitoneally injection of diazoxide, 50mg/kg, once a day for 10 days. The rats in pulmonary hypertension group were injected physiological saline every day, 3mL/kg. Normal control group (NCG): the rats were raised as usual. Paraffinembedded lung sections were stained with HE and Sirius red, and lung blood vessel wall thickness and the lumen size were observed by microscopy, and collagens Ⅰ and Ⅲ were detected by polarization microscopy. Results In the pulmonary hypertension group, the lung blood vessel walls were thicker, the blood lumens were narrower than those in the diazoxide blockage group. Collogen Ⅰ and Ⅲ contents between the lung interstitium were obviously higher than those in the diazoxide blockage group. Conclusion Diazoxide may resist pulmonary interstitial fibrosis and lung blood vessel reconstruction caused by oxygen deficiency. 　　KEY WORDS: hypoxia pulmonary artery hypertension; diazoxide; collagen protein; pathogenesis 　　低氧性肺动脉高压(hypoxia pulmonary artery hypertension, HPH)是临床