去甲汉黄芩素对急性低压低氧诱导脑组织损伤的改善作用研究
Ameliorative effect of norwogonin on brain tissue injury induced by acute hypobaric hypoxia
景临林 1邹蓓蕾 1王格格 2马慧萍1
作者信息
- 1. 中国人民解放军联勤保障部队第九四○医院药剂科,全军高原医学实验室,甘肃兰州 730050;西安交通大学第一附属医院药学部,陕西西安 710061
- 2. 中国人民解放军联勤保障部队第九四○医院药剂科,全军高原医学实验室,甘肃兰州 730050
- 折叠
摘要
目的:研究去甲汉黄芩素改善急性低压低氧诱导小鼠脑组织损伤的作用与机制.方法:将雄性BALB/c小鼠78只随机分成6组:正常对照组,低压低氧组,芦丁组(200 mg·kg-1),去甲汉黄芩素低剂量(50 mg·kg-1)、中剂量(100 mg·kg-1)和高剂量组(200 mg·kg-1).药物组腹腔注射给药,正常对照组和低压低氧组腹腔注射生理盐水.将小鼠置于模拟海拔8000 m的低氧舱中暴露24 h以构建急性低压低氧脑组织损伤模型.HE染色评估脑组织病理变化;试剂盒检测脑组织中H2O2、MDA、SOD和GSH的水平以评估氧化应激状态;ELISA检测脑组织中IL-1β、TNF-α和IL-6的含量以评估炎性反应;Western blot检测缺氧相关蛋白(HIF-1α和VEGF)、抗氧化应激相关蛋白(Nrf2和HO-1)、炎性相关蛋白(NF-κB和TNF-α)以及凋亡相关蛋白(Bax、Bcl-2和Cleaved caspase3)的表达.结果:与正常对照组相比,低压低氧组小鼠脑组织出现病理学改变,脑组织中H2O2、MDA、IL-1β、TNF-α和IL-6 的含量显著升高,SOD和 GSH水平显著降低,HIF-1α、VEGF、Nrf2、HO-1、NF-κB、TNF-α、Bax和Cleaved caspase-3蛋白表达升高,Bcl-2蛋白表达降低,Bax/Bcl-2的比值升高.去甲汉黄芩素预处理能够逆转这些变化.结论:去甲汉黄芩素通过抑制氧化应激、炎性反应和细胞凋亡缓解急性低压低氧诱导的小鼠脑组织损伤.
Abstract
OBJECTIVE To explore the effects and mechanisms of norwogonin(Now)in ameliorating brain tissue injury induced by acute hypobaric hypoxia(AHH)in mice.METHODS A total of 78 male BALB/c mice were randomized into six groups of normal control,HH,rutin(200 mg·kg-1),low-dose(50 mg·kg-1),medium-dose(100 mg·kg-1)and high-dose(200 mg·kg-1)norwogonin.Drugs were administered by an intraperitoneal injection in normal control group.HH groups received saline intraperitoneally.Mice were exposed to a low-oxygen chamber at a simulated altitude of 8 000 m for 24 h for modeling of AHH-induced brain tissue injury.Hematoxylin eosin(HE)stain was utilized for assessing pathological changes.The levels of hydrogen peroxide(H2O2),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in brain tissues were measured for assessing the state of oxidative stress.Enzyme-linked immunosorbent assay(ELISA)was employed for detecting the levels of interleukin-1β(IL-1β),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in brain tissues for assessing inflammatory responses.Western blot was utilized for quantifying the expression levels of hypoxia-related proteins[hypoxia-inducible factor-1α(HIF-1α)& vascular endothelial growth factor(VEGF)],antioxidative stress-related proteins[nuclear factor erythroid 2-related factor 2(Nrf2)& heme oxygenase 1(HO-1)],inflammation-related proteins[nuclear factor kappa-B(NF-κB)& TNF-α]and apoptosis-related proteins[Bcl-2-associated X protein(Bax)&B cell lymphoma 2(Bcl-2)& cleaved cas-pase-3].RESULTS As compared with control group,brain tissues of HH group showed some pathological changes.The levels of H2O2,MDA,IL-1β,TNF-α and IL-6 rose markedly while the levels of SOD and GSH declined significantly.Also the expres-sions of VEGF,Nrf2,HO-1,NF-κB,TNF-α,Bax and cleaved caspase-3 were elevated,the expression of Bcl-2 dropped and the ratio of Bax/Bcl-2 spiked.Norwogonin pretreatment reversed these changes.CONCLUSION Norwogonin alleviates AHH-induced brain tissue injury in mice through suppressing oxidative stress,inflammatory responses and apoptosis.
关键词
急性低压低氧/去甲汉黄芩素/脑损伤/氧化应激/炎性反应/细胞凋亡Key words
acute hypobaric hypoxia/norwogonin/brain injury/oxidative stress/inflammatory response/cell apoptosis引用本文复制引用
出版年
2024
NETL
NSTL
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