肝细胞生长因子对低氧性肺动脉高压小鼠的影响：一项初步研究。
Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study.
机构信息
Department of Cardiovascular and Thoracic Surgery, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
出版信息
Zhongguo Dang Dai Er Ke Za Zhi. 2022 Aug 15;24(8):936-941. doi: 10.7499/j.issn.1008-8830.2203127.
OBJECTIVES
To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH.
METHODS
After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery.
RESULTS
Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (<0.05).
CONCLUSIONS
Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.
目的
研究肝细胞生长因子（HGF）与缺氧性肺动脉高压（HPAH）小鼠治疗反应之间的关系，以及 HGF 作为 HPAH 新型靶向药物的可能性。
方法
成功建模后，将 HPAH 模型小鼠随机分为两组：HPAH 组和 HGF 治疗组（尾静脉注射重组小鼠 HGF 1mg/kg），每组 10 只。10 只正常小鼠作为对照组。5 周后，使用超声心动图测量三尖瓣峰值速度、右心室收缩压、右心室肥厚指数和右心室/体重比；使用格里斯法测量血清中一氧化氮的含量；酶联免疫吸附法测量血清内皮素-1 水平；透射电子显微镜观察肺动脉超微结构变化。
结果
与 HGF 治疗组和正常对照组相比，HPAH 组三尖瓣峰值速度、右心室收缩压、右心室肥厚指数和右心室/体重比明显升高（<0.05）。透射电镜显示 HPAH 组血管内皮细胞大量破坏，小动脉内膜弹性膜排列紊乱，出现破裂和丢失。HGF 治疗组血管内皮细胞结构基本完整，动脉内膜弹性膜结构基本正常。与正常对照组和 HGF 治疗组相比，HPAH 组血清中一氧化氮和内皮素-1 水平明显升高（<0.05）。
结论
增加血清 HGF 水平可以减轻 HPAH 对小鼠心血管系统的影响，可能通过修复内皮细胞损伤、改善血管重塑、恢复肺血管正常的血管舒缩功能。
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