环状八肽OCP2对高原缺氧小鼠心肌组织损伤的保护作用研究OA
Effect of cyclic octapeptide OCP2 on myocardial tissue damage in mice exposed to high-altitude hypoxia
目的 探讨环状八肽OCP2对高原缺氧小鼠心肌损伤的保护作用及潜在分子机制.方法 将60只BALB/c小鼠随机均分为空白对照(Control)、缺氧模型(Model)、乙酰唑胺(ACZ)以及OCP2低、中、高剂量(OCP2-L/M/H)组.各组腹腔单次注射相应药物10 min后,置于模拟海拔8 000 m的低压氧舱内.24 h后采集心脏组织,用于心肌病理学观察、氧化应激及炎症因子水平检测,并测定缺氧诱导因子1α(HIF-1α)、核因子E2相关因子2(Nrf2)、过氧化物酶体增殖激活受体-γ辅激活因子-1α(PGC-1α)及过氧化物酶体增殖物激活受体(PPARγ)的蛋白表达量.结果 与空白对照组相比,缺氧模型组心肌细胞出现排列紊乱、肿胀、染色变浅,病理评分显著增加(P＜0.01);过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)含量明显下降(P＜0.01),而丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)以及HIF-1α、Nrf2的表达水平均显著上升(P＜0.01);同时PGC-1α和PPARγ表达显著降低(P＜0.05或P＜0.01).相较于缺氧模型组,各OCP2剂量组的心肌病理评分显著降低(P＜0.05或P＜0.01),细胞肿胀及排列不齐等病变明显改善;SOD、CAT、GSH水平以及PGC-1α、PPARγ蛋白表达均明显回升(P＜0.05或P＜0.01),而TNF-α、IL-1β、IL-6、MDA及HIF-1α、Nrf2的表达均显著下降(P＜0.05或P＜0.01).结论 OCP2对高原缺氧诱发的小鼠心肌组织损伤具有良好保护效应,其机制可能与其有效抑制HIF-1α活性、阻断HIF-1α与Nrf2及PPARγ/PGC-1α信号轴之间的协同有关,从而最终抑制炎症因子释放并提升抗氧化能力.
Objective Exploring the protective effects and potential molecular mechanisms of cyclic peptide OCP2 on myocardial injury in mice exposed to high altitude hypoxia.Methods Sixty male BALB/c mice were divided randomly into Control,Model,acetazolamide(ACZ),and OCP2 low-,medium-,and high-dose(OCP2-L/M/H)groups.After single intraperitoneal administration of the corresponding medication for 10 minutes,each group was placed in a simulated altitude environment of 8 000 m.Heart tissue was collected 24 hours later to observe pathological changes in myocardial tissue and measure levels of oxidative stress and inflammatory factors,including hypoxia-inducible factor 1α(HIF-1α),nuclear factor erythroid 2-related factor 2(Nrf2),peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α),and peroxisome proliferator-activated receptor γ(PPARγ).Results Compared with the Control group,myocardial tissue cells in the Model group were disordered and swollen,with lighter staining and significantly higher pathological scores(P＜0.01).Superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels were significantly decreased(P＜0.01),malondialdehyde(MDA),tumor necrosis factor(TNF)-α,interleukin(IL)-1 β,IL-6,HIF-1α,and Nrf2 expression levels were significantly increased(P＜0.01),and PGC-1α and PPARγ levels were markedly decreased(P＜0.05 or P＜0.01).Compared with the Model group,pathological scores of cardiac tissue in each OCP2-dose group were significantly reduced(P＜0.05 or P＜0.01)and muscle fiber swelling and misalignment were alleviated.The SOD,CAT,and GSH contents and expression levels of PGC-1α and PPARγ were significantly increased(P＜0.05 or P＜0.01),while the TNF-α,IL-1β,IL-6,and MDA contents HIF-1α,and Nrf2 expression levels were significantly decreased(P＜0.05 or P＜0.01).Conclusions OCP2 can protect against myocardial tissue damage in high-altitude hypoxic mice,possibly via the effective inhibition of HIF-1α activity,thereby disrupting its synergistic effect with Nrf2 and PPARγ/PGC-1αsignaling axes,ultimately inhibiting the production of inflammatory factors and improving antioxidant capacity.
张佩;魏旭;章自会;蒲中枢;张梅;高玉海;申栋帅;陈克明
兰州理工大学生命科学与工程学院,兰州 730050||中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050兰州理工大学生命科学与工程学院,兰州 730050||中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050兰州理工大学生命科学与工程学院,兰州 730050||中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050中国人民解放军联勤保障部队第九四〇医院基础医学实验室,兰州 730050||甘肃省干细胞与基因药物重点实验室,兰州 730050
医药卫生
环状八肽OCP2高原缺氧小鼠心肌组织
cyclic octapeptide OCP2high-altitude hypoxiamousemyocardial tissue
《中国比较医学杂志》 2026 (11)
46-54,9
甘肃省科技重大专项(24ZDFA008)甘肃省自然科学基金(24JRRA010,25JRRA432).
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