HGF过表达对慢阻肺小鼠肺功能、肺动脉压力的影响及其作用机制

目的探讨肝细胞生长因子(HGF)过表达对慢性阻塞性肺疾病小鼠肺功能、肺动脉压力的影响及相关机制。方法取30只小鼠建立慢阻肺模型,随机分为模型组、HGF组、HGF+PI3K抑制剂LY294002组,各10只,另取10只小鼠设为对照组。各组小鼠给予相应处理后,采用实验仪器检测肺功能和肺动脉压力指标,ELISA法检测肺组织爱帕琳肽(Apelin)水平,RT-PCR检测肺组织HGF mRNA表达量,Western blot检测肺组织相关蛋白表达量,TUNEL法检测肺组织细胞凋亡。结果与对照组比较,模型组小鼠mPAP水平升高,TV、PEF、PIF、FEV0.3、FEV0.3/FVC、Apelin水平降低,肺组织HGF mRNA和蛋白表达量降低,Caspase-3表达量和细胞凋亡率升高,Bcl-2表达量、p-PI3K/PI3K和p-Akt/Akt比值降低,差异均有统计学意义(P<0.05)。HGF过表达可显著逆转模型组上述指标水平,LY294002显著抑制HGF过表达对慢阻肺小鼠的作用效果。结论HGF可通过增加Apelin水平、抑制细胞凋亡改善慢阻肺小鼠肺功能和肺动脉压力,其作用机制可能与PI3K/Akt信号通路的激活相关。

Effect of HGF overexpression on pulmonary function and pulmonary artery pressure in mice with chronic obstructive pulmonary disease and its mechanism

Objective To investigate the effect of Hepatocyte growth factor(HGF)overexpression on pulmonary function and pulmonary artery pressure in mice with Chronic obstructive pulmonary disease and its mechanism.Methods The Chronic obstructive pulmonary disease model was established in 30 mice,which were randomly divided into the model group,HGF group,HGF+PI3K inhibitor LY294002 group,each composed of 10 mice.Another 10 mice were set as a control group.The mice in each group were given corresponding treatment,lung function and pulmonary artery pressure were detected by the experimental instrument,the level of Apelin in lung tissue was detected by ELISA,the expression of HGF mRNA in lung tissue was detected by RT-PCR,the expression of related proteins in lung tissue was detected by Western blot,and the apoptosis of lung tissue was detected by TUNEL.Results Compared with the control group,the level of mPAP in the model group was increased,while the level of TV,PEF,PIF,FEV0.3,FEV0.3/FVC,and Apelin were decreased,the expression levels of HGF mRNA and protein of lung tissues were decreased,the expression level of Caspase-3 protein and apoptosis were increased,the protein expression level of Bcl-2,p-PI3K/PI3K,and p-Akt/Akt ratios were decreased,the differences were statistically significant(P<0.05).HGF overexpression could significantly reverse the above indexes levels in the model group,and LY294002 could significantly inhibit the effect of HGF overexpression on chronic obstructive pulmonary disease mice.Conclusion HGF can improve pulmonary function and pulmonary artery pressure in mice with chronic obstructive pulmonary disease by increasing Apelin level and inhibiting apoptosis,and its mechanism may be related to the activation of the PI3K/Akt signaling pathway.