骨形态发生蛋白4 mRNA在低氧大鼠肺血管中的表达

Expression of bone morphogenetic protein 4 mRNA in pneumoangiogram of hypoxic Rats

目的观察骨形态发生蛋白4（BMP4）mRNA在低氧性肺动脉高压大鼠肺血管中的表达及其与低氧性肺动脉高压形成的关系。方法将20只雄性SD大鼠随机分为对照组和低氧组,常压低氧3周建立大鼠肺动脉高压模型,以导管法测定平均肺动脉压（mPAP）,分离并分别称量大鼠右心室（RV）和左心室加室间隔（LV＋S）,计算出右心室肥厚指数RV/（LV＋S）。采用图像分析法测定和计算出肺小动脉管壁厚度指标即管壁厚度占外径的百分比（WT%）和管壁面积占总面积的百分比（WA%）,并采用原位杂交方法检测大鼠肺小动脉管壁BMP4 mRNA的表达水平。结果①对照组mPAP为（16.47±1.11）mm Hg,低氧组大鼠为（29.01±0.86）mm Hg,较对照组明显升高（P〈0.01）。低氧组RV/（LV＋S）为（31.13±2.57）%,对照组仅为（23.12±1.38）%（P〈0.01）。②对照组肺小动脉厚度指标为[WT%：（12.63±0.92）%;WA%：（45.24±1.98）%],而低氧组则明显升高,分别为[WT%：（26.06±1.86）%;WA%：（76.07±5.44）%]（P均〈0.01）。③对照组和低氧组大鼠肺小动脉BMP4 mRNA的染色强度分别为（0.16±0.01）、（0.27±0.03）,低氧组BMP4 mRNA表达明显增加（P〈0.01）。结论低氧大鼠肺血管BMP4 mRNA表达明显增加,BMP4可能在低氧性肺动脉高压的形成中具有重要作用。

Objective To observe the expression of bone morphogenetic protein 4（BMP4） mRNA in hypoxic hypertension rats pneumoangiogram,and its relation with hypoxic hypertension. Methods Twenty male Sprague-Drawley rats were randomly allocated into two groups., control group and hypoxic group. The animal model of hypoxic pulmonary hypertension was established by exposing the rats to normobaric hypoxic condition for three weeks. The mean pulmonary pressure（mPAP） was measured by inserting catheter. The right ventricle（RV） and left ventricle plus septum （LV＋ S） of the rat were weighed respectively and the RV/（LV＋S） was calculated. The index of wall thickness of rat pulmonary arteriole （WT%）-percentage of the wall thickness in the external diameter and（WA%）-percentage of the wall area in the total vascular area were measured by a computerized image analyzer. The expressing level of BMP4 mRNA in pulmonary artererioles were measured by in-situ hybridization. Results （1）In control group the mPAP and RV/（LV＋S） were （16.47±1.11） mm Hg and （23.12±1.38） % ,in hypoxic group,however,they increased to （29.01 ±0.86） mm Hg and （31.13± 2.57）% （P〈0.01 respectively）. （2）In control group the indexes of wall thickness of rat pulmonary arteriole were [WT%： （12.63±0.92）%; WA% ： （45.24±1.98） % ], while in hypoxic group they were [WT% ： （26.06 ± 1.86） % ; WA% ： （ 76.07± 5.44）%] （ p 〈 0.01 ）, which raised more obviously compared with the control group （ P d0.01）. （3）The positive degree of BMP4 mRNA in control group and hypoxic group was （0.16±0.01） and （0.27±0.03） separately,the latter increased more significantly compared with the former（ P 〈0.01）. Conclusions The expression of BMP4 mRNA in hypoxic rats pneumoangiogram increased obviously,and BMP4 may play an important role in the hypoxic pulmonary hypertension.