摘要
目的:氯化血红素(heme chloride,Hemin)是天然血红素的体外纯化形式,是抗贫血和抗肿瘤药物的重要原材料。本研究旨在分析Hemin对低压氧舱模拟高原性缺氧小鼠组织损伤的保护作用,探讨其在抗高原性缺氧中的作用。方法:随机取30只雄性BALB/c小鼠,分成空白组、阳性药组(乙酰唑胺,200 mg/kg)、Hemin低剂量组(Hemin,15 mg/kg)、Hemin中剂量组(Hemin,30 mg/kg)、Hemin高剂量组(Hemin,60 mg/kg),腹腔注射给药,通过常压密闭缺氧实验探究Hemin的抗缺氧活性,以及筛选最佳给药剂量。随机取36只雄性BALB/c小鼠,分成空白组、缺氧组、阳性药组、Hemin高剂量组,在低压氧舱缺氧24 h,测定不同组别的血浆炎症因子水平和心肌、脑组织、肺组织、肝组织的氧化应激指标如丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH)和超氧化物歧化酶(superoxide dismutase,SOD)的水平;采用HE染色观察小鼠组织病理损伤程度;缺氧探针哌莫硝唑检测Hemin对组织缺氧损伤的保护程度。结果:与空白组相比,阳性药组、Hemin中和高剂量组小鼠的存活时间显著延长(均P<0.05),其中Hemin高剂量组的延长率最高。与缺氧组相比,Hemin高剂量组的小鼠脑组织SOD活力水平、GSH含量显著升高,肺组织MDA含量显著降低(均P<0.05);HE染色和缺氧探针结果表明Hemin对缺氧小鼠肝、心、脑和肺组织造成的损伤具有明显的改善作用,对脑组织损伤改善作用最明显。结论:Hemin对缺氧所致的氧化应激、炎症反应有明显的改善作用,对缺氧所致的组织损伤有明显的保护作用。
Objective:Heme chloride(Hemin)is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs.This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice,and explore its role in anti-plateau hypoxia.Methods:Thirty male BALB/c mice were randomly divided into a blank group,a positive drug group(acetazolomide,200 mg/kg),a Hemin low-dose group(15 mg/kg),a Hemin medium-dose group(30 mg/kg),and a Hemin high-dose group(60 mg/kg)with intraperitoneal injection.The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened.Thirty-six male BALB/c mice were randomly divided into a blank group,a hypoxia group,a positive drug group,and a Hemin high-dose group.The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)levels of myocardium,brain,lung,and liver tissues were measured in different groups with hypoxia for 24 h.The degree of histopathological damage of mice was observed with HE staining.The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole.Results:Compared with the blank group,the survival time of mice in the positive drug group,the Hemin medium-dose group,and high-dose group was significantly extended(all P<0.05),with the highest prolongation rate in the Hemin high-dose group.Compared with the hypoxia group,mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue,and a significant decrease in MDA content of lung tissue(all P<0.05).The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver,heart,brain and lung tissues of mice with hypoxia,and the most obvious effect on that of the brain tissue.Conclusion:Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia,and has obvious protective effect on tissue damage caused by hypoxia.
作者
郭茜文
尹紫悦
程俊飞
张晓静
王荣
李文斌
GUO Qianwen;YIN Ziyue;CHENG Junfei;ZHANG Xiaojing;WANG Rong;LI Wenbin(Department of Pharmacy,940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army,Key Laboratory of the Plateau Medicine,Lanzhou 730050;School of Pharmacy,Gansu University of Traditional Chinese Medicine,Lanzhou 730050,China)
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2023年第10期1437-1444,共8页
Journal of Central South University ：Medical Science
基金
国家自然科学基金(82173738)
中国人民解放军联勤保障部队第九四〇医院科研计划项目(2021yxky005)
医学科技青年培育计划拔尖项目(20QNPY070)。
关键词
氯化血红素
高原性缺氧
药效学
heme chloride
plateau hypoxia
pharmacodynamics
