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目的:观察低氧对小鼠肺组织中骨形态发生蛋白4(bone morphogenetic protein,BMP4)内源性拮抗蛋白基因Gremlin mRNA表达的影响。方法:实验选用5周雄性同种系BMP4+/+C57BL/6J纯合子小鼠将其完全随机分为5组:即正常对照组(n=3)、低氧1天组(n=3)、低氧3天组(n=3)、低氧7天组(n=4)和低氧21天组(n=3)。采用实时定量PCR检测Gremlin mRNA表达水平;BMP4+/-C57BL/6J杂合子小鼠分为常氧1天组和低氧1天组。结果:①BMP4+/C57BL纯合子小鼠低氧1天组Gremlin mRNA相对表达量(2.8±0.3)较正常对照组升高(P<0.05)。②低氧3天组,低氧7天组,低氧21天组GremlinmRNA相对表达量差异有统计学意义[(1.9±0.19),(2.2±0.49),(0.26±0.23),P<0.05]。③BMP4+/-C57BL/6J杂合子小鼠常氧1天组Gremlin mRNA相对表达量为(0.92±0.06);低氧1天组Gremlin mRNA相对表达量为(1.04±0.34)(P<0.05)。低氧第一天表达明显增加,低氧21天FSN Gremlin mRNA的表达明显下降,而且低于正常表达;常氧及低氧状态下,BMP4+/+C57BL/6J纯合子小鼠和BMP4+/-C57BL/6J杂合子小鼠肺组织内Gremlin mRNA的表达差异无统计学意义(P>0.05)。结论:Gremlin mRNA的表达随小鼠缺氧的时间呈先上升后下降的趋势,Gremlin这种BMP内源性拮抗蛋白在低氧状态下mRNA的表达上调依赖BMP4 mRNA的表达上调,随着低氧时间的延长Gremlin可能在低氧性肺动脉高压发病机制中起着不同的调节作用。
AIM: To observe the effect of hypoxia on the expression of Gremlin mRNA, an endogenous antagonist protein of bone morphogenetic protein 4 (BMP4), in mice. Methods: The experiment was randomly divided into 5 groups: normal control group (n = 3), hypoxic 1 day group (n = 3), normal control group Hypoxia 3 days group (n = 3), hypoxia 7 days group (n = 4) and hypoxia 21 days group (n = 3). Gremlin mRNA expression levels were detected by real-time quantitative PCR. BMP4 +/- C57BL / 6J heterozygous mice were divided into normoxic 1 day group and hypoxia 1 day group. Results: ① The relative expression of Gremlin mRNA in BMP4 + / C57BL mice was lower than that in control group (2.8 ± 0.3) (P <0.05). ② The relative expression levels of Gremlin mRNA in hypoxia 3 days group, hypoxia 7 days group and hypoxia 21 days group were significantly different ([1.9 ± 0.19], (2.2 ± 0.49), (0.26 ± 0.23), P <0.05] . The relative expression of Gremlin mRNA in BMP4 +/- C57BL / 6J heterozygous mice on day 1 was (0.92 ± 0.06), and that on day 1 was 1.04 ± 0.34 (P <0.05). The expression of FSN Gremlin mRNA in hypoxia decreased significantly on the first day and was lower than that on the 21th day after hypoxia. In normal and hypoxic conditions, BMP4 + / + C57BL / 6J homozygous mice and BMP4 +/- C57BL There was no significant difference in the expression of Gremlin mRNA in the lungs of mice / 6J heterozygous mice (P> 0.05). CONCLUSIONS: The expression of Gremlin mRNA first increases and then decreases with the time of anoxia in mice. The up-regulation of mRNA expression of Gremlin, BMP endogenous antagonist protein in hypoxia state, is dependent on BMP4 mRNA expression. With hypoxia Gremlin may play a different regulatory role in the pathogenesis of hypoxic pulmonary hypertension.