目的 基于蛋白激酶B（protein kinaseB，Akt）/细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）/核因子-κB（nuclear factor-κB，NF-κB）通路探究松果菊苷对缺氧性肺动脉高压（hypoxic pulmonary hypertension，HPH）新生大鼠肺血管重塑的影响。方法 按照随机数字表法将Wistar新生大鼠分为对照组、模型组、大花红景天口服液（1.78mL/kg）组、松果菊苷（40mg/kg）＋Akt激活剂SC79（0.04μg/kg）组和松果菊苷低、高剂量（15、40mg/kg）组，每组12只。除对照组外，其余组大鼠缺氧15d制备HPH模型；对照组大鼠不进行缺氧处理。从缺氧第1天至第15天，各给药组给予相应药物，检测各组大鼠在第3、7、11、15天的肺动脉压；末次给药24h后，检测各组大鼠右心室肥大指数；采用苏木素-伊红（HE）染色检测各组大鼠肺血管形态，并计算肺小动脉中层血管壁厚度占肺小动脉外径的百分比（MT）、肺小动脉中层横截面积占总横截面积的百分比（MA）；采用Masson染色检测各组大鼠肺组织纤维化；采用Westernblotting检测大鼠肺组织中Akt/ERK/NF-κB信号通路相关蛋白表达。结果 与对照组比较，模型组大鼠肺动脉压、右心室肥大指数、MT、MA、胶原纤维面积占比均显著升高（P＜0.05），肺组织中p-Akt、p-ERK1、p-NF-κB p65蛋白表达水平均显著升高（P＜0.05）；与模型组比较，松果菊苷各剂量组和大花红景天口服液组以上指标均显著降低（P＜0.05）；Akt激活剂SC79明显减弱了高剂量的松果菊苷对HPH新生大鼠肺血管重塑的保护作用（P＜0.05）。结论 松果菊苷能够通过抑制Akt/ERK/NF-κB信号通路抑制HPH新生大鼠的肺血管重塑。

Objective To investigate the effect of echinacoside on pulmonary vascular remodeling of neonatal rats with hypoxic pulmonary hypertension (HPH) based on protein kinase B (Akt)/extracellular regulated protein kinase (ERK)/nuclear factor-κB (NF- κB) pathway.Methods Wistar neonatal rats were randomly divided into control group, model group, Rhodiola Oral Liquid (大花红 景天口服液, 1.78 mL/kg) group, echinacoside (40 mg/kg) + Akt activator SC79 (0.04 μg/kg) group and echinacoside low- and highdose (15, 40 mg/kg) groups, with 12 rats in each group. Except the control group, rats in other groups were hypoxic for 15 d to prepare HPH model; Rats in control group were not treated with hypoxia. From 1st day to 15th day of hypoxia, corresponding drugs were given to each administration group, and pulmonary artery pressure of rats in each group was detected on 3rd, 7th, 11th and 15th day. 24 h after the last administration, right ventricular hypertrophy index of rats in each group was detected. Hematoxylin-eosin (HE) staining was used to detect the pulmonary vascular morphology of rats in each group, and percentage of thickness of pulmonary arterioles’ middle vascular wall to the outer diameter of pulmonary arterioles (MT) and percentage of pulmonary arterioles’ middle cross-sectional area to the total cross-sectional area (MA) were calculated. Masson staining was used to detect pulmonary fibrosis of rats in each group. The expressions of Akt/ERK/NF-κB signaling pathway related proteins in lung tissue of rats were detected by Western blotting.Results Compared with control group, pulmonary artery pressure, right ventricular hypertrophy index, MT, MA and percentage of collagen fiber area in model group were significantly increased (P<0.05), p-Akt, p-ERK1 and p-NF-κB p65 protein expressions in lung tissue were significantly increased (P<0.05). Compared with model group, the above indexes in each dose group of echinacoside and Rhodiola Oral Liquid group were significantly decreased (P<0.05). Akt activator SC79 obviously weakened the protective effect of high-dose echinacoside on pulmonary vascular remodeling in neonatal rats with HPH (P<0.05).Conclusion Echinacoside can inhibit pulmonary vascular remodeling in neonatal rats with HPH by inhibiting Akt/ERK/NF-κB signaling pathway.

R285.5