摘要
目的探讨肺心汤对低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)模型大鼠低氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响及其治疗HPH的作用机制。方法将40只健康雄性SD大鼠随机分为正常对照组、模型组、肺心汤组和硝苯地平组,每组10只。采用常压间断缺氧法复制HPH大鼠模型。除正常对照组外,其余各组均置于自制的有机玻璃缺氧舱中饲养,每天缺氧8h,持续14天后,正常对照组及模型组以30mL/kg蒸馏水灌胃;肺心汤组及硝苯地平组以相应药物灌胃(28g/kg、20mg/kg),均每天1次,连续灌胃14天,且在给药同时继续间断缺氧14天。末次给药后次日行平均肺动脉压力(mean pulmonary arter ypressure,mPAP)检测、肺小动脉形态学检测,测定肺动脉管壁面积/管总面积比值(WA%);分别采用免疫组织化学及原位杂交技术检测HIF-1α和VEGF的蛋白及mRNA表达。结果与正常对照组比较,模型组mPAP、WA%、HIF-1α和VEGF蛋白及mRNA表达明显增加(P<0.01,P<0.05);与模型组比较,肺心汤组mPAP、WA%、HIF-1α和VEGF蛋白及mRNA表达明显减少(P<0.01,P<0.05)。结论肺心汤通过降低HIF-1α的表达而下调其靶基因VEGF的表达,部分逆转肺血管平滑肌重塑可能是其治疗HPH的作用机制之一。
Objective To explore the effects of Feixin Decoction （FXD） on the hypoxia-inducible factor- la （HIF-la） and vascular endothelial growth factor （VEGF） in the rat model of hypoxic pulmonary hypertension （HPH）, and to study its mechanisms for treating HPH. Methods Forty healthy male SD rats were randomly di- vided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifediping group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia meth- od. Except the normal control group, rats in the rest groups were fed in a self-made hypoxic plexiglass cabin, with the poor oxygen condition for 8 h daily for 14 successive days. Then the distilled water （at 30 mL/kg） was given by gastrogavage to rats in the normal control group and the HPH model group. FXD （at 28 g/kg） and Nife- diping （ at 20 mg/kg） were given by gastrogavage to rats in the FXD group and the Nifediping group respectively, once daily, for 14 successive days. Besides, hypoxia was continued for 14 days while medicating. The mean pulmonary artery pressure （mPAP） was detected on the second day after the last medication. The morphology of the pulmonary arteriole was detected. The ratio of pulmonary artery wall area and tube area （WA%） was deter- mined. The protein and mRNA expressions of HIF-la and VEGF were detected using immunohistochemistry and in situ hybridization technique. Results Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-la and VEGF significantly increased in the model group （P 〈 0.01, P 〈 0.05）. Compared with the HPH model group, mPAP, WA%, and the protein and mRNA expressions of HIF-la and VEGF significantly decreased in the FXD group （ P 〈0.01, P 〈0.05）. Conclusions FXD down-regulated the ex- pression of VEGF through decreasing the expression of HIF-1 a. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular sm
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2012年第5期676-680,共5页
Chinese Journal of Integrated Traditional and Western Medicine
基金
湖南省中医药科研计划项目重点课题(No.2009007)
关键词
肺心汤
肺动脉高压
低氧诱导因子
血管内皮生长因子
Feixin Decoction
pulmonary arterial hypertension
hypoxia inducible factor
vascular endo-thelial growth factor
