替米沙坦对野百合碱诱导大鼠肺动脉高压的影响及机制研究

Effect and mechanism of telmisartan on monocrotaline-induced pulmonary hypertension in rats

目的探讨替米沙坦激活的过氧化物酶体增殖物激活受体γ(PPARγ)对大鼠肺动脉高压的影响及其机制。方法皮下注射野百合碱复制大鼠肺动脉高压模型,将大鼠分为模型组、治疗组、干预组及对照组。治疗组每天给予替米沙坦10 mg/kg灌胃处理,模型组不予治疗,干预组在治疗组基础上给予GW96625 mg/kg腹腔注射。3周后取材,测量各组大鼠右心室收缩压(RVSP),肺动脉平均压(mPAP),计算右心室肥大指数(RVHI),苏木精-伊红染色观察肺动脉炎症反应情况,酶联免疫吸附试验检测肺组织匀浆中TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)水平,Western blotting检测PPARγ表达差异。结果4组mPAP、RVSP及RVHI比较,差异有统计学意义(P<0.05),模型组较对照组高(P<0.05),治疗组、干预组较模型组低(P<0.05),干预组RVHI高于治疗组(P<0.05)。模型组和干预组PPARγ相对表达量较对照组降低(P<0.05),治疗组较模型组升高(P<0.05)。模型组、治疗组、干预组MCP-1、IL-6及TNF-α水平较对照组升高(P<0.05),治疗组、干预组较模型组降低(P<0.05),干预组较治疗组升高(P<0.05)。结论替米沙坦对野百合碱诱导的大鼠肺动脉高压有预防作用,可能与其激活PPARγ,抑制炎症反应有关。

Objective To investigate the effect of telmisartan-activated peroxisome proliferator-activated receptorγ(PPARγ)on the inflammatory response of rat pulmonary hypertension.Methods The rat pulmonary hypertension model was constructed by subcutaneous injection of monocrotaline.The rats were divided into pulmonary hypertension model group,telmisartan treatment group,GW9662 intervention group and blank control group.The treatment group was given telmisartan(10 mg/kg)daily,and the model group was not treated.The intervention group was given GW9662(5 mg/kg)intraperitoneally on the basis of telmisartan(10 mg/kg)per day.After 3 weeks,the right ventricular systolic pressure,the mean pulmonary artery pressure,the right ventricular hypertrophy index,the pulmonary inflammatory response were observed by HE staining,the levels of TNF-α,IL-6 and MCP-1 in lung tissue homogenate were detected by ELISA,and the expression of PPARγwas detected by Western blot.Results There were significant differences in mPAP,RVSP and RVHI levels among the four groups(P<0.05),higher in the model group than in the control group(P<0.05),lower in the treatment group and the intervention group than in the model group(P<0.05),and higher in the intervention group than in the treatment group(P<0.05).The relative expression of PPARγin the model group and the intervention group was lower than that in the control group(P<0.05),and that in the treatment group was higher than that in the model group(P<0.05).The levels of MCP-1,IL-6 and TNF-αin the model group,the treatment group and the intervention group were higher than those in the control group(P<0.05),the treatment group and the intervention group were lower than those in the model group(P<0.05),and the intervention group were higher than those in the treatment group(P<0.05).Conclusions The preventive effect of telmisartan on monocrotaline-induced pulmonary hypertension in rats may be related to its inhibition of inflammatory response by activation of PPARγ.