汉防己甲素对先天性膈疝大鼠模型肺组织内皮素表达的影响及意义

Effect of tetrandrine on endothelin expression in the lungs and clinical significance thereof:experiment with rat models with nitrofen-induced congenital diaphragmatic hernia

目的探讨汉防己甲素对先天性膈疝动物模型肺发育及肺动脉高压的影响及意义。方法 25只成年雌性 SD 大鼠随机分为5组,每组5只。定时配种成功后,于配种后第9.5天,正常对照组孕鼠每只给予食用油灌胃,膈疝组每只给予 Nitrofen 灌胃。配种后第18.5天,正常对照组每只腹腔内注射生理盐水;各膈疝组分别给予相应的干预措施;配种后第21天对所有孕鼠行剖宫产,取出胎鼠肺组织,将肺组织进行内皮素免疫组化染色和图像分析。结果正常对照组4只雌鼠共产仔38只,均无膈疝形成。膈疝组雌鼠19只共产仔126只,有膈疝形成者57只,致畸率45.2%。图像分析及数据统计结果显示各膈疝组之间内皮素在肺小动脉、细支气管中的表达强度差异有统计学意义。而且肺小动脉和细支气管之间内皮素表达强度以及肺小动脉相对血管壁厚度、相对血管壁面积和肺小动脉相对积分光密度之间存在正相关(r=0.847、0.851、0.844,均 P<0.01)。结论汉防己甲素能明显改善先天性膈疝大鼠模型的肺组织发育不良、减轻肺动脉高压,同时能降低内皮素在肺内的表达强度。汉防己甲素可能是通过抑制肺组织内皮素的合成与释放,抑制内皮素与相应受体结合而发挥其作用的。

Objective To investigate the effects of tetrandrine on endothelin expression in the lungs and its clinical significance. Methods 25 pregnant female SD rats were randomly divided into 5 equal groups： Groups A to D were fed with nitrofen to cause congenital diaphragmatic hernia （CDH） in the fetuses. Group A was injected with normal saline, Group B with dexamethasone （DXM）, Group C with tetrandrine, and Group D with DXM ＋tetrandrine. Group E was control Group. On day 21.5 of pregnancy the fetuses were delivered by cesarean section and killed. Microscopy was used to observe the CDH formation, and the relative wall thickness （RWA） and relative wall area （RWA） of pulmonary arterioles. The lung/body weight ratio, and relative integrated optical density （IOD） of pulmonary arteriole and bronchiole were observed. The expression of endothelin in the lung tissues was detected by immunohistochemistry. Results 9 rats of Group A-D produced 57 fetuses with CDH with a CDH arte of 45. 2%. The lung/body weight ratios, and RWA values of Group A-D were all significantly lower than that of Group E （ all P 〈 0.05 ）. The RWT of pulmonary arteriole was significantly lower in Groups B and C compared with Group E （ both P 〈 0.05 ）. The RWT and RWA of Group A were significantly lower than those of Group B-D （ all P 〈 0. 05 ）. The values of relative IOD of pulmonary tissues and of pulmonary arteriole of Group A-D were all significantly lower than those of Group E （ all P 〈 0.05 ）. A positive correlation existed between the relative IOD of endothelin in pulmonary arteriole and in bronchiole （ P 〈 0.01）, and among the RWT and RWA of pulmonary arteriole, and relative IOD （ all P 〈 0. 01 ）. Conclusion Tetrandrine improves the pulmonary hypoplasia and degrades the pulmonary hypertension.