Chen Zhi-Wen, Li Xiang, Wu Bing-Xia, Ma Ke-Tao, Gu Qiang
Department of Pediatrics, First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang 832000, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2019 Nov;21(11):1124-1130. doi: 10.7499/j.issn.1008-8830.2019.11.013.
To investigate the effects of calcium-sensitive receptors (CaSR) on the expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and cortisol concentration in a neonatal mouse model of persistent pulmonary hypertension (PPH).
Fifty-six newborn C57BL/6 mice were randomly divided into a control group (n=14), a PPH group (n=14), an agonist group (n=14), and an inhibitor group (n=14). The mice in the PPH, agonist, and inhibitor groups were exposed to a 12% oxygen concentration, and the agonist group and inhibitor group were given CaSR agonist (GdCl3, 16 mg/kg) and CaSR antagonist (NPS2390, 1 mg/kg) intraperitoneally once a day, respectively. The mice in control group were exposed to air, and then injected with an equal volume of normal saline as those in the PPH group every day. All mice were treated for 14 days. Morphological examination of heart and lung tissues was performed using hematoxylin-eosin staining. The expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein in lung tissues were measured by qRT-PCR and Western blot respectively. Brain natriuretic peptide (BNP) and cortisol levels in lung tissues were determined using ELISA.
Compared with the control group, the PPH group had significantly increased pulmonary artery wall thickness (WT%), ratio of right to left ventricular thickness (RV/LV), alveolar mean linear intercept, and BNP concentration and a significantly reduced radial alveolar count (P<0.05); compared with the PPH group, the agonist group showed significant increases in WT% and BNP concentration, while the inhibitor group showed significant reductions in the two indicators (P<0.05). Compared with the control group, the PPH group showed significant reductions in the expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant increase in cortisol concentration (P<0.05); compared with the PPH group, the agonist group had significantly lower expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant higher cortisol concentration, while the inhibitor group showed opposite changes in these indicators (P<0.05).
CaSR may control the development and progression of PPH in newborn mice by regulating the expression of 11β-HSD2 and cortisol concentration.
在新生儿持续性肺动脉高压（PPH）小鼠模型中，研究钙敏感受体（CaSR）对2型11β-羟基类固醇脱氢酶（11β-HSD2）表达及皮质醇浓度的影响。
将56只新生C57BL/6小鼠随机分为对照组（n = 14）、PPH组（n = 14）、激动剂组（n = 14）和抑制剂组（n = 14）。PPH组、激动剂组和抑制剂组小鼠暴露于12%氧浓度环境，激动剂组和抑制剂组分别每天腹腔注射一次CaSR激动剂（GdCl3，16 mg/kg）和CaSR拮抗剂（NPS2390，1 mg/kg）。对照组小鼠暴露于空气中，然后每天注射与PPH组等体积的生理盐水。所有小鼠均治疗14天。采用苏木精-伊红染色对心脏和肺组织进行形态学检查。分别通过qRT-PCR和蛋白质印迹法检测肺组织中11β-HSD2 mRNA和11β-HSD2蛋白的表达水平。采用酶联免疫吸附测定法测定肺组织中脑钠肽（BNP）和皮质醇水平。
与对照组相比，PPH组肺动脉壁厚度（WT%）、右心室与左心室厚度比值（RV/LV）、肺泡平均线性截距及BNP浓度显著增加，肺泡计数显著减少（P<0.05）；与PPH组相比，激动剂组WT%和BNP浓度显著增加，而抑制剂组这两项指标显著降低（P<0.05）。与对照组相比，PPH组11β-HSD2 mRNA和11β-HSD2蛋白表达水平显著降低，但皮质醇浓度显著升高（P<0.05）；与PPH组相比，激动剂组11β-HSD2 mRNA和11β-HSD2蛋白表达水平显著降低，但皮质醇浓度显著升高，而抑制剂组这些指标变化相反（P<0.05）。
CaSR可能通过调节11β-HSD2的表达和皮质醇浓度来控制新生小鼠PPH的发生发展。
