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环状多肽OCP 2对高原缺氧小鼠脑组织保护作用OA

The protective effect of cyclic peptide OCP 2 on brain tissue in high-altitude hypoxic mice

中文摘要英文摘要

目的 明确OCP 2的抗高原缺氧活性和对高原缺氧小鼠脑组织的保护作用.方法 观察小鼠在不同给药间隔和不同剂量下常压密闭缺氧存活时间.60只小鼠随机分为空白对照组、缺氧模型组、乙酰唑胺组、OCP 2低、中、高剂量组,每组10只,空白对照组置于屏障环境,其余组置于模拟海拔8000 m.24 h后,脑组织进行病理学分析,测定缺氧相关指标.结果 10 min为最优给药间隔,OCP 2(5~100 mg·kg-1)明显提高常压密闭缺氧小鼠存活时间.与空白对照组相比,缺氧模型组病理评分明显升高;过氧化氢酶(catalase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)含量明显降低,过氧化物酶体增殖物激活 受 体-γ(peroxisome proliferators-activated receptors-γ,PPARγ)及其辅激活因子-1α(PPARγ coactivator 1 alpha,PGC1α)表达量明显降低;白介素-6(interleukin-6,IL-6)等炎症因子、丙二醛(malondialdehyde,MDA)含量及缺氧诱导因子1α(hypoxia-inducible factor 1-alpha,HIF-1α)表达量明显升高.与缺氧模型组相比,OCP 2各组病理评分明显下降;SOD、CAT和GSH含量,PGC-1α和PPARγ表达量明显升高,IL-6等炎症因子和MDA含量及HIF-1α表达量明显降低.结论 OCP 2对高原缺氧小鼠脑损伤有良好的保护作用,可能与提高抗氧化能力、抑制炎症因子和HIF-1α/PGC1α/PPARγ信号通路有关.

Aim To clarify the anti-high-altitude hy-poxia activity of OCP 2 and its protective effect on brain tissue of high-altitude hypoxia mice.Method The survival time of mice under atmospheric pressure and hypoxia at different dosing intervals and doses were observed.Sixty mice were randomly divided into a blank control group,an hypoxia model group,an ac-etazolamide group,and OCP 2 low-,medium-,and high-dose groups,with 10 mice in each group.The blank control group was placed in a barrier environ-ment,while the remaining groups were placed at a simulated altitude of 8000 m.After 24 hours,patho-logical analysis of brain tissue was performed to deter-mine hypoxia related indicators.Results The optimal dosing interval was 10 minutes,and OCP 2(5-100 mg·kg-1)significantly improved the survival time of mice under atmospheric pressure and hypoxia.Com-pared with the blank control group,the pathological score of the hypoxia model group significantly in-creased.The levels of catalase(CAT),superoxide dismutase(SOD),and glutathione(GSH)were sig-nificantly reduced,and the expression levels of peroxi-some proliferators activated receptors-γ(PPAR γ)and its co activator 1 alpha(PGC1 α)were significantly re-duced.The levels of inflammatory factors such as in-terleukin-6(IL-6),malondialdehyde(MDA),and hy-poxia inducible factor 1 alpha(HIF-1 alpha)signifi-cantly increased.Compared with the hypoxia model group,the pathological scores of each OCP2 group sig-nificantly decreased.The levels of SOD,CAT,and GSH,as well as the expression levels of PGC-1 α and PPAR γ,significantly increased,while the levels of in-flammatory factors such as IL-6,MDA,and HIF-1 α expression significantly decreased.Conclusion OCP 2 has a good protective effect on brain injury in mice with high altitude hypoxia,which may be related to im-proving antioxidant capacity,inhibiting inflammatory factors and HIF-1α/PGC1α/PPARγ pathway.

魏旭;张佩;章自会;魏振龙;高玉海;赵映申;冷非凡;申栋帅;陈克明

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医药卫生

OCP 2高原缺氧脑损伤氧化应激炎症反应HIF-1α/PGC1α/PPARγ信号通路

OCP 2high altitudes hypoxiabrain in-juryoxidative stressinflammatory responseHIF-1α/PGC1α/PPARγ signaling pathway

《中国药理学通报》 2026 (4)

651-659,9

甘肃省科技重大专项(No 24ZDFA008)甘肃省自然科学基金资助项目(No 22JR5RA1052,24JRRA010,25JRRA432)

10.12360/CPB202508071

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