舒肺压方对野百合碱诱导肺动脉高压模型大鼠肺动脉压及氧化应激的影响

Effect of Shufeiya Formula(舒肺压方)on Pulmonary Arterial Pressure and Oxidative Stress in Monocrotaline-induced Pulmonary Hypertension Model Rats

目的探讨舒肺压方治疗肺动脉高压的可能作用机制。方法 80只SD大鼠随机分为对照组(20只)和造模组(60只),造模组大鼠采用野百合碱(MCT)单次性腹腔注射60 mg/kg诱导14天建立肺动脉高压模型。将造模成功的50只大鼠随机分为模型组、西地那非组和舒肺压方低、中、高剂量组,每组10只。对照组和模型组大鼠给予1 ml/100 g蒸馏水灌胃,西地那非组给予西地那非溶剂25 mg/kg灌胃,舒肺压方低、中、高剂量组分别给予浓度为0.2925、0.5850、1.1700 g/ml的舒肺压方溶液1 ml/100 g灌胃,各组均每日灌胃1次。灌胃14天后检测大鼠右心室收缩压(RVSP)、平均肺动脉压(mPAP),计算右心室肥厚指数(RVHI),检测血清活性氧(ROS)、丙二醛(MDA)含量及谷胱甘肽过氧化物酶(GSH-Px)及过氧化氢酶(CAT)活性,并通过HE染色观察各组大鼠肺组织病理形态学变化。结果与对照组比较,模型组大鼠RVSP、mPAP、RVHI水平及ROS、MDA含量显著升高,GSH-Px、CAT活性显著降低(P<0.01),HE染色显示肺动脉内皮连续性破坏,肺小动脉血管壁呈现不规则间断性肥厚,管腔部分狭窄。与模型组比较,西地那非组及舒肺压方各剂量组肺动脉管壁厚度及管腔狭窄程度改善明显;西地那非组和舒肺压方中、高剂量组RVSP、mPAP、RVHI显著降低(P<0.05或P<0.01),舒肺压方高、中剂量组ROS、MDA含量降低,CAT活性升高(P<0.05或P<0.01)。与舒肺压方低剂量组比较,舒肺压方高、中剂量组CAT活性显著升高,舒肺压方高剂量组MDA含量显著降低(P<0.01)。结论舒肺压方可降低肺动脉高压模型大鼠肺动脉压及肺动脉病理损伤,减轻氧化应激反应,可能是治疗肺动脉高压的机制之一。

ObjectiveTo explore the possible mechanism of Shufeiya Formula(舒肺压方)on pulmonary arterial hypertension(PAH).Methods group(n=60),and 60 mg/kg monocrotaline(MCT)was intraperitoneally injected for 14 days in the modeling group to establish the PAH model.The successfully modeled 50 rats were randomly divided into a model group,a positive drug group,and Shufeiya Formula low,medium,and high dose groups,with 10 rats in each group.The rats in the control group and the model group were given 1 ml/100 g distilled water by gavage;the positive drug group was given25 mg/kg sildenafil by gavage;the Shufeiya Formula low,medium and high dose groups were administered with Shufeiya Formula solution by gavage at the concentration of 0.2925,0.5850 and 1.1700 g/ml,respectively.The interventions in all groups were administered once daily.After 14 consecutive days,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured;the right ventricular hypertrophy index(RVHI)was calculated;the serum content of reactive oxygen species(ROS)and malondialdehyde(MDA),and the glutathione peroxidase(GSH-Px)and catalase(CAT)activities were detected;HE staining was used to assess the pathomorphological changes of lung tissues.Results mPAP and RVHI,and the content of ROS and MDA in the model group significantly increased,while the GSH-Px and CAT activities significantly decreased(P<0.01);the HE staining results showed that the pulmonary artery endothelium in the model group was continuously destructed;irregular and intermittent hypertrophy were seen in the pulmonary arterioles,and there was partial stenosis of the lumen.Compared to the model group,the positive drug group and Feishuya Formula groups at different doses significantly improved the pulmonary artery wall thickness and lumen stenosis degree;the positive drug group and Feishuya Formula medium and high dose groups had lower RVSP,mPAP and RVHI levels(P<0.05 or P<0.01);Feishuya Formula medium and high dose groups had decreased ROS and MDA content,as well as increased CAT activity(P<0.05 or P<0.01).Compared to those in the Feishuya Formula low dose group,the CAT activity significantly increased in the medium and high dose groups,and the MDA content was reduced in the high dose group(P<0.01).Conclusion Feishuya Formulacan decrease the the pulmonary artery pressure,relieve the pathological damage of pulmonary artery,and reduce the oxidative stress,which may be the possible mechanism of treating PAH.