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藏药红景天减弱高原肺动脉高压大鼠肺小血管病理变化和血管内皮生长因子的增高

白玛康卓, 郭燕, 边巴顿珠, 董海, 汪涛, 罗锋, 文富强, 崔超英^*

西藏大学医学院，拉萨 850000；兰州大学基础医学院病理研究所，兰州 730000；西藏自治区藏医药研究院，拉萨 850000；四川大学华西医院呼吸内科，成都 610041

摘要

本研究旨在观察藏药红景天对高原自然环境下建立的肺动脉高压大鼠模型中肺血管重构和血管内皮生长因子(vascular endothelial growth factor, VEGF)表达的影响，探讨其对高原肺动脉高压的防治作用与机制。健康雄性Wistar大鼠50只，随机分为平原对照组、高原10天组、高原30天组、红景天10天组和红景天30天组，每组10只。平原对照组大鼠在成都(海拔500 m)饲养，高原组和红景天组大鼠空运至拉萨(海拔3 700 m)饲养。红景天组大鼠每日给予24%红景天粗提液(10 mL/kg)灌胃，平原对照组和高原组每日给予等体积生理盐水灌胃，分别饲养10天或30天。用右心漂浮导管技术检测平均肺动脉压(mean pulmonary artery pressure, mPAP)；通过称重计算右心肥大指数[RV/(LV + S)]；用透射电镜观察肺小动脉超微结构；用免疫组织化学法检测肺小动脉壁VEGF的表达。结果显示：(1) 高原10天和30天组大鼠的mPAP、RV/(LV + S)明显高于平原对照组(均P < 0.05)，红景天10天组以上指标与高原10天组相比差异无统计学意义(均P > 0.05)，而红景天30天组以上指标均低于高原30天组(P < 0.05)。(2)电镜显示高原10天组肺小动脉内皮细胞呈柱状并向管腔突出，管腔狭窄，内弹力膜不规则，平滑肌细胞细胞器增多；高原30天组上述病理改变更为明显。红景天10天和30天组大鼠血管壁的改变较同时间点高原组明显减轻。(3)高原10天和30天组大鼠肺小动脉VEGF蛋白的表达较平原对照组增加(均P < 0.05)，而红景天30天组VEGF蛋白表达低于高原30天组(P < 0.05)。以上结果提示，藏药红景天对大鼠高原肺动脉高压具有一定治疗作用，其机制可能与抑制VEGF蛋白的表达有关。

关键词： 红景天; 肺动脉高压; 血管内皮生长因子

分类号：R281.4

[Integripetal rhodiola herb attenuates high altitude-induced pulmonary arterial remodeling and expression of vascular endothelial growth factor in rats.] [Article in Chinese]

BAI Ma-Kang-Zhuo, GUO Yan, BIAN Ba-Dun-Zhu, DONG Hai, WANG Tao, LUO Feng, WEN Fu-Qiang, CUI Chao-Ying^*

Medical College of Tibet University, Lhasa 850000, China； Institute of Pathology, Basic Medical College of Lanzhou University, Lanzhou 730000, China； The Tibetan Medicine Research Institute of the Tibet Autonomous Region, Lhasa 850000, China； Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China

Abstract

The aim of this study was to investigate the effect of integripetal rhodiola herb on pulmonary arterial remodeling and expression of vascular endothelial growth factor (VEGF) in high altitude pulmonary hypertension in rats. Fifty healthy male Wistar rats were divided into five groups randomly: Plain control group (LC group), 10-day plateau group (H10 group), 30-day plateau group (H30 group), 10-day rhodiola-treated plateau group (R10 group), and 30-day rhodiola-treated plateau group (R30 group). Each group included 10 rats. The rats in LC group were kept in Chengdu (500 meters above sea level), and rats in H and R groups were kept in Lhasa (3 700 meters above sea level). The rats in R group were daily treated with integripetal rhodiola herb extract (24%, 10 mL/kg) intragastrically for 10 d or 30 d, while rats in LC and H groups were treated with the same volume of saline. Mean pulmonary arterial pressure (mPAP) was detected via a catheter in the pulmonary artery by pressure waveform monitoring. The ratio value of right ventricle weight to left ventricle plus septum weight [RV/(LV + S)] was measured. The microstructure of pulmonary arterioles was examined by electron microscopy. The expression of VEGF in the lung was investigated using immunohistochemistry. The results showed that mPAP and [RV/(LV + S)] in H10 group and H30 group were higher than those in LC group (P < 0.05); but there was no significant difference between H10 group and R10 group (P < 0.05); and mPAP and [RV/(LV + S)] in H30 group were lower than those in H30 group (P < 0.05). Electron microscopy showed that compared to LC group, arteriolar endothelial cells were arranged in a columnar or palisading form, protruding into the lumen, accompanied with luminal stenosis, irregular internal elastic membrane, and proliferation of vascular smooth muscle cells in H groups, which was more obvious in H30 group than in H10 group; while these pathological changes were attenuated in the R groups compared to H groups. The levels of VEGF protein in H groups were also higher than those in LC group (P < 0.05); while the expression of VEGF in R30 group was lower than that in H30 group. In summary, the results show that the integripetal rhodiola herb can attenuate high altitude-induced pulmonary arterial remodeling in rats, and the inhibition of VEGF protein expression by rhodiola may be one of the mechanisms.

Key words: integripetal rhodiola herb; pulmonary hypertension; vascular endothelial growth factor

收稿日期：2010-10-18　　录用日期：2011-01-24

通讯作者：崔超英　　E-mail: cuisangmu@yahoo.com

引用本文：

白玛康卓, 郭燕, 边巴顿珠, 董海, 汪涛, 罗锋, 文富强, 崔超英. 藏药红景天减弱高原肺动脉高压大鼠肺小血管病理变化和血管内皮生长因子的增高[J]. 生理学报 2011; 63 (2): 143-148.

BAI Ma-Kang-Zhuo, GUO Yan, BIAN Ba-Dun-Zhu, DONG Hai, WANG Tao, LUO Feng, WEN Fu-Qiang, CUI Chao-Ying. [Integripetal rhodiola herb attenuates high altitude-induced pulmonary arterial remodeling and expression of vascular endothelial growth factor in rats.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (2): 143-148 (in Chinese with English abstract).