7-羟乙基白杨素对低压低氧致脑组织损伤的保护作用

Protective Effect of 7-HEC on Brain Tissue Damage Induced by Hypobaric Hypoxia

关键词:  7-羟乙基白杨素  低压低氧  脑损伤  氧化应激  凋亡

Key words:  7-HEC  hypobaric hypoxia  brain damage  oxidant stress  apoptosis

摘要:

目的 研究7-羟乙基白杨素（7-HEC）对低压低氧诱导大鼠脑组织损伤的保护作用。方法 将52只健康♂ Wistar大鼠随机分为正常组、模型组、乙酰唑胺组、7-HEC组，每组13只。连续灌胃给药5 d，末次给药后，除正常组，将其余3组置于低压低氧动物实验舱，升至8 000 m海拔缺氧处理24 h。HE染色观察脑组织病理改变，酶标法检测脑组织中过氧化氢（H₂O₂）和丙二醛（MDA）水平，以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和ATP酶的活力；Western blotting检测蛋白B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白抗体（Bax）及半胱氨酸天冬氨酸特异性蛋白酶3（caspase-3）的表达。结果 与正常组相比，低压低氧导致大鼠脑组织出现明显损伤，H₂O₂和MDA水平显著升高，抗氧化酶SOD、CAT和GSH-Px以及Na⁺-K⁺-ATPase和Ca²⁺-Mg²⁺-ATPase的活力显著降低。7-HEC预处理能够逆转这些变化。此外，低压低氧能够显著升高脑组织中促凋亡蛋白Bax和cleaved caspase-3表达，降低抗凋亡蛋白Bcl-2的表达，而7-HEC能够下调Bax和cleaved caspase-3表达，上调Bcl-2的表达。结论 7-HEC对低压低氧致脑组织损伤具有明显的保护作用，其作用机制可能与其缓解氧化应激，抑制细胞凋亡，改善能量代谢有关。

Abstract:

OBJECTIVE To investigate the protective effect of 7-HEC against hypobaric hypoxia(HH) induced brain injury in rats. METHODS Fifty two ♂ Wistar rats were divided in to normal group, model group, acetazolamide group and 7-HEC group, 13 rats per group. The drugs were intragastrically administrated for 5 consecutive days, except normal group, the rats in other three groups were transferred to 8 000 m in a HH chamber for 24 h after the final administrated. The brain histomorphology of rats were detected by HE staining. Hydrogen peroxide(H₂O₂), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-Px) and ATPase were evaluated using related Kits. The expression of Bcl-2, Bax and cleaved caspase-3 were assessed with Western blotting. RESULTS Compared to normal group, HH induced brain damage as evidenced by the increased level of H₂O₂ and MDA and the decreased of the activity of antioxidant enzyme including SOD, CAT and GSH-Px as well as Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase. Pretreatment with 7-HEC could reverse these changes. Moreover, 7-HEC could inhibit the apoptosis induced by HH via up-regulating the expression of Bax and caspase-3 and down-regulating the expression of Bcl-2. CONCLUSION 7-HEC can suppress the HH-induced brain damage in rats by alleviating oxidative stress, inhibiting apoptosis and improving energy metabolism.