低氧对小鼠肺组织内Follistatin和Follistatin-like3表达的影响

mRNA expression of Follistatin and follistatin-like 3, bone morphogenetic protein-4 antagonists in lung tissues of hypoxic mice

目的 观察低氧对小鼠肺组织中骨形态发生蛋白4（BMP4）内源性拮抗蛋白基因Follistatin（FSN）和follistatin-like 3 （FSRP） mRNA表达的影响.方法 将30只5周龄雄性同种系BMP4＋/＋C57BL/6J野生型小鼠按照随机数字表法分为对照组、低氧1d组、低氧3d组、低氧7d组和低氧21 d组,每组6只;6只BMP4＋/-C57BL/6J杂合子小鼠按照随机表法分成常氧1d杂合组和低氧1d杂合组.分别给予小鼠不同时长低氧环境后处死并采集肺组织,采用实时定量PCR检测肺组织中FSN和FSRP mRNA的表达水平.结果 FSN和FSRP mRNA的表达随小鼠缺氧的时间呈先上升后下降的趋势,低氧第1天表达增加尤其明显,FSN mRNA的表达趋势较FSRP mRNA明显.常氧及低氧状态下,野生型小鼠与杂合子小鼠肺组织内FSN和FSRP mRNA的表达无明显差异,低氧1d组FSN和FSRP mRNA相对表达量分别为（28.0±9.4）和（2.0±0.4）,低氧3d组分别为（6.3±3.2）和（1.7±0.7）,低氧7d组分别为（1.77±0.36）和（1.22 ±0.15）,低氧21 d组分别为（1.04±0.27）和（0.85±0.10）,均高于对照组,差异有统计学意义（均P＜0.05）.常氧1d杂合组小鼠肺组织的FSN和FSRP mRNA相对表达量分别为（0.95±0.05）和（1.11 ±0.03）,低氧1d杂合组分别为（1.10±0.40）和（0.85±0.18）.结论 FSN和FSRP作为内源性拮抗蛋白对低氧状态下mRNA的表达上调依赖于BMP4 mRNA的表达上调,FSN可能在低氧性肺动脉高压发病机制中具有重要的调节作用.

Objective To observe the expression changes of Follistatin（FSN） and follistatin-like 3 （FSRP） mRNA,both of bone morphogenetic protein-4 （BMP4） antagonists,in mice lung tissue under different hypoxic time and its relation with BMP4.Methods Thirty BMP4 ＋/＋ C57BL/6J wild type mice were randomly divided into normoxic control group,and 4 groups including 1 day,3 days,7 days and 21 days under hypoxic condition.The hypoxic animal model was established by exposing the mice to hypoxic condition for different time.The expressing level of FSN and FSRP mRNA in lung tissues were measured by Quantitative Real-Time PCR.Results FSN and FSRP mRNA increased in hypoxic 1 day group as （28.0 ± 9.4） and （2.0 ± 0.4）,in hypoxie 3 day group,FSN mRNA increased by （6.3 ± 3.2） and FSRP mRNA by （1.67 ± 0.7） （P 〈 0.05）.Compared with the normoxic group （1.77 ± 0.36） and （1.22 ± 0.15） （P 〈 0.01）,FSN and FSRP mRNA up-regulated in hypoxic 7 day group.The positive degree of FSN and FSRP mRNAinhypoxic21 day group were （1.04±0.27） and （0.85±0.10）（P〈0.05）.In normoxic 1 day group,FSN mRNA of lung tissues of BMP4 ＋/-C57BL/6J mice was （0.95 ±0.05）;FSRP mRNA was （1.11 ±0.03） （P 〈0.05）.In BMP4 ＋/-C57BL/6J mice lung tissues,FSN mRNA were （1.10 ±0.40） （P 〈 0.05） ;FSRP mRNA were （0.85 ± 0.18）.Conclusions The expression of FSN and FSRP mRN A in hypoxic 1 ;3 ;7 day mice lung tissues increased obviously,and FSN may play an important role in the hypoxic pulmonary hypertension through BMP4.