摘要
目的:通过观察COPD合并肺动脉高压大鼠肺血管病理变化及血管内皮功能的变化,探讨肺络病变与COPD合并肺动脉高压的相关性。方法:采用一次性腹腔注射MCT(60mg/kg)复制COPD合并肺动脉高压大鼠模型,常规饲养28天后处死并收集大鼠血清及肺组织标本。应用HE染色及免疫组织化学技术观察肺小动脉病理形态学变化及VEGF在肺小动脉血管壁的表达;采用放射免疫及硝酸还原酶法分别测定肺组织匀浆中ET-1、NO含量;采用ELISA法测定血清中VEGF水平。结果:模型组大鼠在细支气管周围或其它部位的小动脉可见管腔变小、狭窄,甚至不完全闭锁,血管中膜变厚且平滑肌细胞增生肥厚明显,肺血管损伤明显,内皮细胞变性肿胀增生,突向血管腔内,甚至坏死脱落,免疫组化显示模型组VEGF表达明显高于正常对照组(P<0.01);与正常组相比较模型组大鼠肺组织匀浆中NO表达明显减少(P<0.01),ET-1水平明显升高(P<0.05);模型组血清中VEGF表达明显高于正常组(P<0.01)。结论:一次性腹腔内注射MCT即可引起肺血管内皮细胞损伤、促使大鼠肺小血管结构重建,从而诱导肺动脉高压形成,与COPD渐进为肺动脉高压的病理特点相符合;COPD合并肺动脉高压大鼠肺血管舒缩功能异常与久病入络,导致肺络中气滞、血瘀、津凝或脉络损伤密切相关。
Objective:To explore the Correlations between obstruction of collaterals and COPD with Pulmonary Hypertension,we observed the changes in pathological and vascular endothelial function in rats with COPD and Pulmonary Hypertension. Methods:SD rats were given a single dose of MCT (60 mg/kg) to induce the model of COPD with Pulmonary Hypertension,collected serum and the lung tissue specimens after 4 weeks. The Pathological features of pulmonary arteries were observed and the expression of VEGF in pulmonary artery wall were measured by HE staining and immunohistochemistry technique. The levels of NO and Endothelin-1 (ET-1)in lung homogenate were measured by radio immunoassay (RIA) and nitrate reductase method; Vascular endothelial growth factor (VEGF) in serum was measured by euzymelinked immunosorbent assay respectively.Results:Compared with normal control group,pulmonary artery wall in model group was thicker and lumens was narrower and endothelial dysfunction obviously. The expression of VEGF in pulmonary artery wall of model group was higher than that of normal control group(P〈0.01). Compared with normal control group,the NO in model group decreased(P〈0.01) and the level of ET-1 in lung tissue increased obviously(P〈0.05),the expression of VEGF in serum of model group was significantly higher than that in normal control(P〈0.01).Conclusion:These results indicate that a single intraperitoneal injection of MCT could induce the pulmonary artery wall endothelial dysfunction ,pulmonary vascular remodeling,lead to increased pulmonary artery pressure which correspond to the pathology character of COPD developing Pulmonary Hypertension. The pulmonary vasomotor dysfunction in rats with COPD and Pulmonary Hypertension were closely related with invalidism result in either qi depression to blood stasis or diseases on pulmonary collaterals.
出处
《中华中医药学刊》
CAS
2010年第6期1247-1249,共3页
Chinese Archives of Traditional Chinese Medicine
基金
浙江省中医药科技计划项目(2004C032)