芪参益气滴丸对低压缺氧大鼠多器官损伤的保护作用及机制研究

Protective effects and mechanisms of Qishen Yiqi Dripping Pills on multi-organ injury in low-pressure hypoxia rats

关键词:  芪参益气滴丸  急性高原病  水通道蛋白4  低氧诱导因子-1α  血管内皮细胞生长因子受体2

Key words:  Qishen Yiqi Dripping Pills  acute mountain sickness  AQP4  HIF-1α  VEGFR2

摘要:

[目的] 建立急性高原病（AMS）大鼠模型，探究芪参益气滴丸（QSYQ）对低压缺氧大鼠多器官损伤的保护作用及其分子机制。[方法] 不同剂量芪参益气滴丸预防给药7 d后，低压氧舱模拟8 000 m海拔制备AMS大鼠模型，检测脑、肺湿干比率，采用小动物超声评估心功能，肺功能仪测定肺功能，伊文思蓝染色法检测血脑屏障通透性，生化试剂盒检测血清超氧化物歧化酶（SOD）、丙二醛（MDA）水平，苏木精-伊红（HE）染色观察心脑肺病理改变，免疫组化染色分析脑、肺组织中水通道蛋白4（AQP4）表达水平，蛋白免疫印迹（Western blot）法检测脑、肺组织低氧诱导因子-1α（HIF-1α）和血管内皮细胞生长因子受体2（VEGFR2）蛋白表达。[结果] 芪参益气滴丸降低AMS大鼠脑、肺水肿程度，改善心肺功能，降低血脑屏障通透性，抑制氧化应激，改善低氧对脑、肺组织病理学损伤。AMS大鼠脑、肺组织中AQP4、HIF-1α和VEGFR2蛋白表达显著提升，芪参益气滴丸能够明显抑制其表达。[结论] 芪参益气滴丸对AMS大鼠心、脑、肺组织器官损伤具有保护作用，可能通过HIF-1α/VEGF和AQP4通路发挥作用。

Abstract:

[Objective] To establish a rat model of acute mountain sickness（AMS） and investigate the protective effect of Qishen Yiqi Dripping Pills on multi-organ damage in rats with low-pressure hypoxia and its molecular mechanism. [Methods] After different doses of Qishen Yiqi Dripping Pills were administered for 7 days，the AMS rat model was prepared in a low-pressure oxygen chamber simulating an altitude of 8 000 m. Brain and lung wet-dry weight ratios were detected，cardiac function was evaluated by small animal ultrasound，lung function was determined by pulmonary function meter，blood-brain barrier permeability was detected by Evans blue staining，serum SOD and MDA levels were detected by biochemical kit，and pathological changes in the heart，brain，and lungs were observed by HE staining. Immunohistochemical staining was used to analyse the expression level of AQP4 protein in brain and lung tissues，and Western blot detected the expression of HIF-1α and VEGFR2 protein in brain and lung tissues. [Results] Qishen Yiqi Dripping Pills reduced the degree of brain and lung oedema，improved cardiopulmonary function，lowered the permeability of blood-brain barrier，inhibited oxidative stress，and ameliorated the pathological damage of brain and lung tissues caused by hypoxia in AMS rats. The expression of AQP4，HIF-1α，and VEGFR2 proteins was significantly elevated in the brain and lung tissues of AMS rats，and Qishen Yiqi Dripping Pills markedly inhibited this elevation. [Conclusion] Qishen Yiqi Dripping Pills has a protective effect on organ damage in heart，brain and lung tissues of AMS rats，and may act through the HIF-1α/VEGF and AQP4 pathways.