水飞蓟素对肺动脉高压大鼠心室重构的作用研究

Effect of silymarin on ventricular remodeling in pulmonary hypertension rats

目的研究水飞蓟素对野百合碱(MCT)诱导的肺动脉高压大鼠的治疗效果及机制。方法将SD大鼠随机分为模型组、对照组和实验组,每组15例。通过右侧背部皮下注射MCT(60 mg·kg^-1)建立肺动脉高压模型,对照组注射等量生理盐水;注射后第2天实验组大鼠灌胃水飞蓟素80 mg·kg^-1,而模型组和对照组则给予等量0.9%NaCl,连续给药4周。检测各组干预后右心室肥厚指数(RVHI)及平均肺动脉压、平均颈动脉压;以苏木精-伊红(HE)染色观察肺组织病理形态;以实时荧光定量聚合酶链反应(qPCR)检测NADPH氧化酶4(NOX4)mRNA的表达。结果干预结束后,对照组、模型组和实验组大鼠平均肺动脉压分别为(10.15±1.73),(26.33±1.63)和(21.46±1.74)mmHg,平均颈动脉压分别为(94.48±15.27),(163.77±16.79)和(133.14±14.26)mmHg,RVHI分别为0.26±0.06,0.53±0.13和0.34±0.09,NOX4 mRNA表达量分别为1.26±0.31,3.89±0.16和2.45±0.09,差异均有统计学意义(均P<0.05)。结论水飞蓟素可降低肺动脉高压大鼠肺动脉压及颈动脉压,抑制心室重构,可能与抑制NOX4 mRNA表达有关。

Objective To investigate the therapeutic effect and mechanism of silymarin on monocrotaline(MCT)induced pulmonary hypertension in rats.Methods SD rats were randomly divided into model group,control group and test group,with 15 rats in each group.The pulmonary hypertension rat model was established by subcutaneous injection of MCT(60 mg·kg^-1)into the right back of the rats.Control group was injected with the same amount of normal saline.Test group was gavage with silymarin(80 mg·kg^-1)the next day,while model group and control group were given the same amount of 0.9%NaCl.The drug was administered continuously for 4 weeks.Right ventricular hypertrophy index(RVHI),mean pulmonary artery pressure,mean carotid artery pressure were measured after intervention in each group,and pulmonary histopathology was observed by hematoxylin-eosin(HE)staining.The expression of NADPH oxidase 4(NOX4)mRNA was detected by real-time quantitative polymerase chain reaction(qPCR).Results After intervention,the mean pulmonary artery pressure of control group,model group and test group were(10.15±1.73),(26.33±1.63),(21.46±1.74)mmHg,carotid artery pressure were(94.48±15.27),(163.77±16.79),(133.14±14.26)mmHg,RVHI were 0.26±0.06,0.53±0.13,0.34±0.09,the expression of NOX4 mRNA were 1.26±0.31,3.89±0.16,2.45±0.09,all with significant difference(all P<0.05).Conclusion Silymarin can reduce pulmonary artery pressure and carotid artery pressure and inhibit ventricular remodeling in rats with pulmonary hypertension,which may be related to the inhibition of NOX4 mRNA expression.