钙敏感受体及相关分子在新生大鼠持续肺动脉高压发病中的作用

Roles of calcium receptor and its related factors in the pathogenesis of persistent pulmonary hypertension in newborn rats

目的探讨钙敏感受体(CaSR)及相关分子在持续肺动脉高压(PPH)新生大鼠肺组织中的表达及在PPH发病机制中的作用。方法选取6只Sprague-Dawley(SD)孕鼠,孕第19天时随机分为PPH组和对照组,每组3只。PPH组孕鼠置于12%氧浓度的缺氧箱中并腹腔内注射吲哚美辛0.5 mg/kg,2次/天,连续3天,建立胎鼠肺动脉高压模型;对照组孕鼠暴露在空气中并腹腔内注射等量生理盐水。两组孕鼠均于孕第22天行剖宫产,对照组、PPH组分别获取新生大鼠26、28只,两组各随机抽取15只仔鼠用于后续实验。采用RT-PCR技术检测新生大鼠肺组织CaSR mRNA及Ⅱ型11β羟基类固醇脱氢酶(11β-HSD2)mRNA表达,采用蛋白质印迹法检测新生大鼠肺组织CaSR蛋白和一氧化氮(NO)含量。结果与对照组比较,PPH组新生大鼠肺组织中CaSR mRNA[(0.592±0.052)比(0.408±0.017)]及蛋白表达[(0.717±0.027)比(0.445±0.011)]升高,NO含量[(1.50±0.20)μmol/g比(0.37±0.16)μmol/g]升高,11β-HSD2 mRNA[(0.413±0.073)比(0.978±0.079)]表达降低,差异均有统计学意义(P<0.05)。结论 CaSR及相关分子在新生大鼠PPH发病中可能发挥重要作用。

Objective To study the expression of calcium receptor （CaSR） and its related factors in lung tissue of an persistent pulmonary hypertension （PPH） newborn rat model. Methods Six pregnant Sprague-Dawley （SD） rats were randomly assigned to PPH group and control ~roup （3 in each group） on the 19th day of pregnancy. Pregnant rats assigned to PPH group were exposed to 12% oxygen and injected with indomethacin （0. 5 mg/kg） intraperitoneally twice daily for three days, in order to build a fetal rat PPH model. The rats in control group were injected with equal volume of normal saline intraperitoneally and exposed to air. Neonatal rats were born by caesarean section from both groups on the 22nd day of pregnancy. The expression of CaSR and type Ⅱ 11β-hydroxysteroid dehydrogenase （ 11β-HSD2） in the lung tissue of neonatal rats were detected by RT-PCR and Western blot, and the content of nitric oxide （NO） was also detected. Results The levels of mRNA [ （0. 592± 0. 052） vs.（0. 408 ±0. 017）, P 〈0. 05] and protein [ （0. 717 ±0. 027） vs. （0. 445±0. 011 ） ] of CaSR in the lung tissue were higher in the PPH group than in the control group, the content of NO [ （ 1.50± 0. 20） μmol/g vs. （0. 37 ± 0. 16 ）μmol/g, P 〈 0. 05 ] was also higher, while 11β-HSD2 [ （ 0. 413 ± 0. 073 ） vs. （0. 978 ± 0. 079）, P 〈 0. 05 ] in the lung tissue were lower in the PPH group than that in the control group. Conclusions CaSR and 11 β-HSD2 may play important roles in the pathogenesis of PPH in neonatal rats.