11β-HSD2及相关信号分子在新生大鼠持续性肺动脉高压发病中的作用

Roles of type Ⅱ 11β-hydroxysteroid dehydrogenase and its signaling factors in pathogenesis of persistent pulmonary hypertension in neonatal rats

目的探讨肺组织中II型11β-羟基类固醇脱氢酶(11β-HSD2)及相关信号分子在新生大鼠持续性肺动脉高压(PPH)发病中的作用。方法 6只Sprague-Dawley大鼠在孕第19天随机分为PPH组和对照组,每组3只,其中PPH组置于12%的氧浓度中及腹腔内注射吲哚美辛0.5 mg/kg,每日两次,连续3 d,建立胎鼠肺动脉高压模型;对照组暴露在空气中并同时腹腔注射等量生理盐水。对照组和PPH组于孕第22天剖腹分别获取新生大鼠28只、31只,两组分别随机处死15只新生大鼠。采用激光共聚焦技术观察11β-HSD2在新生大鼠肺组织中的表达,ELISA检测PPH大鼠血清中皮质醇及肺组织中前列环素、肾素、血管紧张素、醛固酮的浓度。结果 11β-HSD2在对照组及PPH组大鼠肺组织广泛表达。与对照组比较,PPH组肺组织中11β-HSD2及前列环素的表达降低(P<0.05),而血清皮质醇及肺组织中肾素、血管紧张素、醛固酮的表达增高(P<0.05)。结论 11β-HSD2及相关信号分子在新生大鼠PPH的发生发展中发挥了作用。

Objective To study the roles of type II 11β-hydroxysteroid dehydrogenase（11β-HSD2） and it’s signaling factors in the lung tissue in pathogenesis of persistent pulmonary hypertension（PPH） in neonatal rats. Methods Six Sprague-Dawley rats on the 19 th day of pregnancy were randomly divided into PPH and control groups（n=3 each）. The PPH group was intraperitoneally injected with indomethacin（0.5 mg/kg） twice daily and exposed in 12% oxygen for three days, in order to prepare a fetal rat model of PPH. The control group was intraperitoneally injected with an equal volume of normal saline and exposed to air. Neonatal rats were born by caesarean section from both groups on the 22 nd day of pregnancy. In each group, 15 neonatal rats were randomly selected and sacrificed. 11β-HSD2 expression in the lung tissue of neonatal rats were observed by Confocal laser technology, and serum cortisol levels and prostacyclin, renin, angiotensin and aldosterone in the lung tissue of both groups were measured using ELISA. Results 11β-HSD2 protein was widely expressed in the lung tissue of the control and PPH groups. The levels of 11β-HSD2 and prostacyclin in the lung tissue were lower in the PPH group than in the control group, while serum cortisol levels and renin, angiotensin and aldosterone in the lung tissue were higher in the PPH group than in the control group（P〈0.05）. Conclusions 11β-HSD2 and it’s signaling factors play roles in pathogenesis of PPH in neonatal rats.