摘要
目的观察低氧性肺动脉高压大鼠肺组织中骨形成蛋白2(BMP-2)的变化及 BMP 在低氧诱导内皮细胞凋亡中的作用,探讨 BMP 在低氧性肺动脉高压发病中的作用。方法将20只雄性 Wistar 大鼠随机分为2组,低氧组经常压低氧处理3周,建立大鼠低氧性肺动脉高压模型,采用免疫组织化学染色法观察大鼠肺组织中 BMP-2的表达。用图像分析技术检测大鼠肺小动脉形态改变及 BMP-2表达强度的变化。建立人脐静脉内皮细胞(HUVEC)低氧培养模型,加入 BMP 阻断剂Noggin,用流式细胞仪检测细胞凋亡率。结果低氧3周后,大鼠平均肺动脉压(mPAP)为(29.5±0.9)mm Hg(1 mm Hg=0.133 kPa),与对照组的(16.3±0.5)mm Hg 比较明显增加;低氧大鼠肺小动脉管壁增厚、管腔狭窄,表现为管壁厚度占外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%)明显升高,分别为(27±7)%和(80±8)%,对照组分别为(16±5)%和(54±11)%,两组相比差异有统计学意义(P<0.01);低氧组肺小动脉壁 BMP-2积分吸光度值(IA)为13 463±5755,对照组为6124±1199,两组相比差异有统计学意义(P<0.01),且与 WT%和 WA%呈明显正相关(r 值分别为0.744和0.693,P<0.01)。低氧诱导内皮细胞凋亡增加,低氧24 h 时的细胞凋亡率为(14.23±1.01)%,48 h 时为(25.21±8.58)%;低氧前预先加入 Noggin,低氧24 h 时细胞凋亡率为(11.91±0.57)%,48 h 时为(15.01±0.15)%,差异有统计学意义(P<0.01)。结论慢性低氧时 BMP-2表达增多;低氧诱导内皮细胞凋亡,BMP 阻断剂可抑制低氧诱导的内皮细胞凋亡;BMP 在低氧性肺动脉高压发病过程中起一定的作用。
Objective To investigate the change of bone morphogenetic protein-2 （BMP-2） in the lung tissues of rats with hypoxic pulmonary hypertension （HPH） and the role of BMP in the apoptosis of endothelial cells exposed to hypoxia. Methods Twenty male Wistar rats were randomly divided into two groups, the HPH group and the control group, 10 rats in each group. The HPH model was established by placing the rats in an isobaric chamber [ 02 = （ 10 ±0.5） % ] for three weeks. The distribution of BMP-2 in pulmonary tissues was observed by using streptavidin peroxidase method （ SP）, and the morphologic changes of pulmonary arterioles and the integrated optical density （IA） of BMP-2 were determined by image analysis. The effect of Noggin （ a blocking agent of BMP） on the apoptosis of hypoxic cultivated human umbilical vein endothelial cells （HUVEC） was assayed by flow cytometers. Results Compared to the control group, pulmonary artery hypertension was evident in the hypoxic rats： mPAP was 16. 3 ±0.5 mm Hg （1 mm Hg = 0. 133 kPa） vs （ 29. 5± 0. 9 ） nun Hg, P 〈 0. 01. In the hypoxic rats, the pulmonary arteriolar wall thickened significantly; WT% was （16±5）% vs （27 ±7）%, and WA% was （54 ± 11）% vs （80 ± 8） %, both P 〈 0.01. The distribution of BMP-2 was mainly in the pulmonary arteriolar walls. The IA of BMP-2 significantly increased （6124 ± 1199 vs 13 463 ± 5755, P 〈 0. 01 ）, and showed a positive linear relationship to WT% and WA% respectively （ WT%. r = 0. 744 P 〈 0. 01 ; WA% ： r = 0. 693 P 〈 0. 01 ）. Hypoxia induced apoptosis of HUVEC; the apoptosis rate was increased from 6% to 14% and 25% after exposure to hypoxia for 24 h and 48 h respectively. The HUVEC apoptosis rate induced by hypoxia was reduced by Noggin to 11.91% （ 24 h） and 15.01% （48 h）. Conclusions Chronic hypoxia induced an increased expression of BMP-2, and a blocking agent of BMP inhibited the apoptosis of endothelial cells induced by hypoxia. It suggests that BMP may play an important role in the pathogenesis of hypoxic pulmonary hypertension.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2007年第9期662-666,共5页
Chinese Journal of Tuberculosis and Respiratory Diseases
关键词
低氧血
高血压
肺性
脱噬作用
骨形成蛋白
Anoxemia
Hypertension,pulmonary
Apoptosis
Bone morphogenetic protein
