心力衰竭大鼠血液亚甲基四氢叶酸还原酶和CITED2基因表达水平与血气波浪式信号的相关性研究  

Study on the correlation between blood MTHFR and CITED2 gene expression levels and blood pressure waveform information in rats with heart failure

作　　者：程帆[1] 朱艳霞[1] 刘琴[1] 司小敏[1] CHENG fan;ZHU Yan-xia;LIU Qin;SI Xiao-min(Cardiopulmonary rehabilitation center,Taihe Hospital of Shiyan City,Shiyan 442000,China)

机构地区：[1]十堰市太和医院心肺康复中心,湖北省十堰市442000

出　　处：《中国心血管病研究》2022年第1期77-83,共7页Chinese Journal of Cardiovascular Research

基　　金：湖北省卫生健康卫科研项目(WJ2019M062);十堰市科学技术局引导性科研项目(19Y50)。

摘　　要：目的研究心力衰竭(HF)大鼠血液亚甲基四氢叶酸还原酶(MTHFR)基因和c AMP反应元件结合蛋白/P300互作反式激活因子2(CITED2)基因的表达水平与血气波浪式信号的相关性。方法 SPF级8周龄的雌性Wistar大鼠建立HF模型大鼠分为Sham组和HF组(n=8)。Sham组大鼠仅暴露左冠状动脉前降支和HF组进行左冠状动脉前降支结扎。手术后7周监测血流动力学指标,和血气波浪式信号,收集术后1周、3周、7周大鼠的血液,7周后安乐死大鼠收集心脏组织。使用HE染色法观察大鼠心脏病理变化,q RTPCR检测1周、3周、7周大鼠血液汇总MTHFR和CITED2基因的表达,试剂盒法检测血液MTHFR和CITED2基因启动子区的甲基化水平。皮尔森相关性检测法分析MTHFR和CITED2基因表达和血气波浪式信号的相关性。结果 HF组血液MTHFR和CITED2的表达[(2.51±0.52)和(3.19±0.24)]高于Sham组[(1.00±0.00)和(1.00±0.00),t=12.079、9.635,P<0.05]。HF组血液MTHFR和CITED2[(0.78±0.06)和(1.05±0.11)]的启动子区甲基化水平低于Sham组[(1.22±0.31)和(1.67±0.27),t=13.821、15.633,P<0.05]。HF组中MTHFR水平与血氧分压(Pa O2)[(6.01±1.29)mm Hg]和动脉血氧饱和度(Sa O2)(0.19±0.04)%呈负相关性(t=-0.521、-0.786,P<0.05)。CITED2水平与Sa O2呈负相关性(t=-0.839,P<0.05)。结论 HF大鼠血液MTHFR和CITED2基因表达升高与血氧饱和度降低有关。Objective To study the correlation between the expression level of methylenetetrahydrofolate reductase(MTHFR) gene and c AMP response element binding protein binding protein/P300 interaction transactivator 2(CITED2) gene and blood gas wave signal in heart failure(HF) rats.Method The HF model rats were established in 16 SPF 8-week-old female Wistar rats and divided into the Sham group and HF group.In the sham group,only the left anterior descending coronary arteries were exposed.In the HF group,the left anterior descending coronary arteries were ligated.7 w after the operation,hemodynamic indicators and blood pressure waveform information were monitored.Blood was collected from the rats at 1 w,3 w,and 7 w after the operation.After 7 w,the heart tissues were collected.The changes of the heart in rats were observed by using the HE staining method.Real-time quantitative PCR(q RT-PCR) was used to detect the expression of MTHFR and CITED2 genes in rat blood at 1 w,3 w and 7 w.Methylation levels in the promoter regions of MTHFR and CITED2 genes were detected by Methylation Detection Kits.The Pearson correlation detection method was used to analyze the correlation between the expressed levels of MTHFR and CITED2 and blood gas wave signals.Result The expressed levels of blood MTHFR and CITED2 [(2.51±0.52) and(3.19±0.24)] in the HF group were significantly up-regulated compared with the Sham group [(1.00 ± 0.00) and(1.00 ± 0.00),t=12.079,9.635;P<0.05].The methylation levels of the promoter regions of blood MTHFR and CITED2 [(0.78±0.06) and(1.05±0.11)] in the HF group were downregulated than those in the Sham group [(1.22±0.31) and(1.67±0.27),t=13.821,15.633,P<0.05].In the HF group,there was a negative correlation between MTHFR level and partial pressure of blood oxygen(Pa O2)(6.01±1.29) mm Hg and arterial oxygen saturation(Sa O2) [(0.19±0.04)%,t=-0.521,-0.786,P<0.05].The CITED2 level was in negative correlation with Sa O2(t=-0.839,P<0.05).Conclusion The increased expression of blood MTHFR and CITED2 is related to

关 键 词：心力衰竭 亚甲基四氢叶酸还原酶 cAMP反应元件结合蛋白/P300互作反式激活因子2 血气波浪式信号 启动子区甲基化 

分 类 号：Q95-33[生物学—动物学] R541.6[医药卫生—心血管疾病]