He Hong-Jun, Dai Ai-Guo
Graduate School of University of South China, Hunan 421001.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 May;32(5):676-80.
To explore the effects of Feixin Decoction (FXD) on the hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in the rat model of hypoxic pulmonary hypertension (HPH), and to study its mechanisms for treating HPH.
Forty healthy male SD rats were randomly divided into four groups, i. e., the normal control group, the HPH model group, the FXD group, and the Nifedipine group, 10 rats in each group. The HPH rat model was prepared using normal pressure intermittent hypoxia method. 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 Nifedipine (at 20 mg/kg) were given by gastrogavage to rats in the FXD group and the Nifedipine 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 determined. The protein and mRNA expressions of HIF-1alpha and VEGF were detected using immunohistochemistry and in situ hybridization technique.
Compared with the normal control group, mPAP, WA%, and the protein and mRNA expressions of HIF-1alpha 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-1alpha and VEGF significantly decreased in the FXD group (P < 0.01, P < 0.05).
FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1alpha. One of its mechanisms for treating HPH might be partially due to reversing the remodeling of pulmonary vascular smooth muscle.
探讨肺心汤（FXD）对缺氧性肺动脉高压（HPH）大鼠模型中缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的影响，并研究其治疗HPH的机制。
将40只健康雄性SD大鼠随机分为四组，即正常对照组、HPH模型组、FXD组和硝苯地平组，每组10只。采用常压间歇缺氧法制备HPH大鼠模型。除正常对照组外，其余各组大鼠置于自制的缺氧有机玻璃舱内饲养，每日低氧环境8小时，连续14天。然后正常对照组和HPH模型组大鼠灌胃给予蒸馏水（30 mL/kg）。FXD组和硝苯地平组大鼠分别灌胃给予FXD（28 g/kg）和硝苯地平（20 mg/kg），每日1次，连续14天。此外，给药期间持续缺氧14天。末次给药后第2天检测平均肺动脉压（mPAP）。检测肺小动脉形态。测定肺动脉壁面积与管腔面积之比（WA%）。采用免疫组织化学和原位杂交技术检测HIF-1α和VEGF的蛋白及mRNA表达。
与正常对照组比较，模型组mPAP、WA%以及HIF-1α和VEGF的蛋白及mRNA表达均显著升高（P < 0.01，P < 0.05）。与HPH模型组比较，FXD组mPAP、WA%以及HIF-1α和VEGF的蛋白及mRNA表达均显著降低（P < 0.01，P < 0.05）。
FXD通过降低HIF-1α的表达下调VEGF的表达。其治疗HPH的机制之一可能部分是由于逆转肺血管平滑肌的重塑。
