常压低氧性肺动脉高压p53基因表达及意义的试验研究

目的研究常压低氧性肺动脉高压大鼠肺内p53基因的表达及探讨肺血管重建（PVR）的分子机制。方法20只雄性SD大鼠随机分为对照组、低氧组,每组10只。采用常压间断低氧8h/d,连续21d的方法来建立常压低氧性肺动脉高压（HPH）模型。用右心导管法检测肺动脉平均压（mPAP）。测量右心室肥厚指数R.（L＋S）-1]。测量肺血管管壁面积占血管总面积的百分比（MA%）、管壁厚度占血管外径的百分比（MT%）及管腔面积占血管总面积的百分比（VA%）等肺血管形态学指标。用免疫组化方法来检测p53基因在HPH大鼠肺组织表达。结果21d后,低氧组mPAP、R.（L＋S）-1、MT%、MA%及p53基因表达较对照组明显升高（P〈0.01或P〈0.05）,而VA%较对照组明显降低（P〈0.01）。结论HPH大鼠肺内突变型p53基因的表达明显增强,而可能相对抑制野生型p53基因蛋白的表达,导致细胞增殖被促进、细胞凋亡被抑制,从而导致PVR进展,引起肺动脉压力升高,以致发生HPH。

Expression and Effects of p53 in Pulmonary of Rats After 21 days' Hypoxia and Pulmonary Vascular Remodeling

Objective To investigate the expression of mutated p53 in pulmonary of rats after 21 days＇ hypoxia, and investigate the cause of pulmonary vascular remodeling（PVR） in hypoxic pulmonary hypertension（HPH） rats. Methods 20 healthy Spraque--Dawley male rats were randomly divided into two groups： esntrol group（n=10）, hypoxic group（n=10）. Then the model of hypoxic pulmonary hypertension were established by exposing rats to normobaric hypoxic conditions for 8 hours one day in 3 weeks continually except rats of control group.At first, mean pulmonary arterial pressure（mPAP） was measured by a right cardiac catheterization. Then, right ventricular hypertrophy was represented as the ratio of right ventricular weight to left ventricular weight plus septum weight RV- （LV＋S）-1]. Leica Qwin Image Analyzer was used to measure the vascular morphologic indexes of pulmonary in rats：（MA%）,（MT%） and（VA%）. Immunohistochemical staining Method （SP） was used to examine the expression of p53 in paraffin--embedded specimens of rats pulmonary tissue. Results After 21 days＇ hypoxia, mPAP, RV-（LV＋S）-1,MT%,VA% and expression of p53 in hypoxic group increased obviously higher than control group（P〈0.01orP〈0.05）, VA% decreased higher than control group（P〈0.01）. Conclusion Expression of mutated p53 gene was obviously increased, and expression of wild gene p53 was possibly decreased in pulmonary of rats after 21 days＇ hypoxia, which resulted in enhancing cell proliferation and decreasing apoptosis, then improved the development of PVR and HPH finally.