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目的动态观察内源性尾加压素Ⅱ(urotensinⅡ,UⅡ)在慢性低氧高二氧化碳性肺动脉高压大鼠不同节段肺细小动脉的表达,以探讨其在肺动脉高压发生发展中的作用。方法对不同低氧时间(1、2、4周)的大鼠模型:(1)测定平均肺动脉压力(mPAP),右心室游离壁(RV)和左心室加室间隔(LV+S)的重量比。(2)免疫组化方法检测不同节段肺细小动脉UⅡ蛋白的表达。(3)光镜下观察三级肺细小动脉显微结构的变化,用图像分析仪心肺血管分析软件测定肺细小动脉管壁面积/管总面积(WA/TA)和肺细小动脉中膜厚度(PAMT)。结果(1)mPAP、RV/LV+S的比较:低氧高二氧化碳各组均高于正常对照组(P<0.01);2周组比1周组分别高22.5%与14.1%(P均<0.01);4周组与2周组无显著差别(P>0.05)。(2)免疫组化显示三级肺细小动脉(近端至远端)UⅡ蛋白表达的平均吸光度值1周组较正常对照组分别高40.4%、38.9%、22.9%(P均<0.01);2周组较1周组分别高15.2%、14.7%、16.6%(P均<0.01);而4周组与1周组间无显著差别。(3)肺小动脉显微结构的变化:4HH组各级血管均有显著重构,1HH组无明显变化,2HH组介于两者之间。结论慢性低氧高二氧化碳性大鼠肺动脉高压形成过程中,肺内各级细小动脉的UⅡ的表达均呈现明显的上调,并与肺动脉压升高、右心室肥大的程度基本一致,提示UⅡ在慢性低氧高二氧化碳性肺动脉高压的形成机制中具有重要的病理生理意义。
Objective To observe the expression of endogenous urotensin Ⅱ (UⅡ) in different segments of pulmonary arterioles in rats with chronic hypoxic hypercapnic pulmonary hypertension to explore its role in the development of pulmonary hypertension. Methods Rat models with different hypoxic periods (1, 2, 4 weeks) were included: (1) The mean pulmonary artery pressure (mPAP), RV free wall (RV) and left ventricular compartment (LV + S) ratio. (2) Immunohistochemistry was used to detect the expression of UⅡprotein in different segments of pulmonary arteries. (3) The changes of the microstructure of the three-grade pulmonary arterioles were observed under light microscope. The pulmonary artery wall area / total tube area (WA / TA) and pulmonary arteriolar intima-media thickness PAMT). Results (1) Comparison of mPAP and RV / LV + S: The hypoxia and hypercapnia groups were higher than the normal control group (P <0.01), 22.5% and 14.1% 0.01). There was no significant difference between 4 weeks group and 2 weeks group (P> 0.05). (2) Immunohistochemistry showed that the mean absorbance of UⅡprotein in the third grade pulmonary arterioles (proximal to distal) were 40.4%, 38.9% and 22.9% higher than those in the normal control group (P <0.01). 2 weeks group were 15.2%, 14.7% and 16.6% higher than those in the 1 week group (all P <0.01), while there was no significant difference between 4 weeks and 1 week groups. (3) Microstructure changes of pulmonary arterioles: There were significant remodeling of blood vessels at all levels in 4HH group, no significant changes in 1HH group, and between 2HH group. Conclusions During the process of pulmonary hypertension in rats with chronic hypoxia and hypercapnia, the expression of UⅡ in all the small arteries in the lungs is significantly increased, which is consistent with the increase of pulmonary arterial pressure and right ventricular hypertrophy. Hypoxic hypercapnic pulmonary hypertension formation mechanism has important pathophysiological significance.