7-羟乙基白杨素对低压缺氧致PC12细胞损伤的改善作用及机制  

Investigation on improvement effects and mechanism of 7-hydroxyethyl chrysin on PC12 cell injury induced by hypobaric hypoxia

作　　者：张冬梅 高迎春 张洁 景临林 马慧萍 ZHANG Dongmei;GAO Yingchun;ZHANG Jie;JING Linlin;MA Huiping(Dept.of Pharmacy,the 940th Hospital of Joint Logistics Support Force of PLA/Lab of PLA for High Altitude Medicine,Lanzhou 730050,China)

机构地区：[1]联勤保障部队第九四〇医院药剂科/全军高原医学实验室,兰州730050

出　　处：《中国药房》2023年第4期402-406,412,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81872796);甘肃省科技计划资助项目(No.22JR11RA014);第九四〇医院院内科研项目(No.2021yxky046,No.2022yxky004)。

摘　　要：目的探讨7-羟乙基白杨素(7-HEC)对低压缺氧致PC12细胞损伤的改善作用及可能机制。方法以大鼠肾上腺嗜铬细胞瘤细胞系PC12为对象,以低压缺氧(5%CO_(2)、94%N2、1%O_(2)、54004 Pa)条件培养,考察不同浓度7-HEC(100、10、1、0.1、0.01μmol/L)对低压缺氧细胞存活率的影响;检测7-HEC(1μmol/L)对低压缺氧细胞中乳酸脱氢酶(LDH)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,凋亡率,周期,以及细胞中活化的胱天蛋白酶3(cleaved caspase-3)、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。结果与对照组比较,低压缺氧组细胞的存活率显著降低(P<0.01);10、1、0.1μmol/L的7-HEC可逆转低压缺氧导致的细胞存活率降低(P<0.05或P<0.01)。与对照组比较,低压缺氧组细胞上清液中LDH含量、细胞中MDA含量、凋亡率、G1期细胞比例和细胞中cleaved caspase-3蛋白的表达水平均显著升高;细胞中SOD活性,S期、G2期细胞比例和细胞中Bcl-2/Bax比值均显著降低(P<0.05或P<0.01)。与低压缺氧组比较,7-HEC组细胞中LDH、MDA含量,凋亡率,G1期细胞比例和cleaved caspase-3蛋白的表达水平均显著降低;SOD活性、G2期细胞比例、Bcl-2/Bax比值均显著升高(P<0.01)。结论7-HEC可明显提高低压缺氧细胞的存活率,降低上清液中LDH含量,改善细胞周期阻滞,降低细胞凋亡率;其对低压缺氧细胞损伤的改善作用可能与抑制caspase-3/Bax/Bcl-2通路的激活有关。OBJECTIVE To investigate the improvement effects and possible mechanism of 7-hydroxyethyl chrysin(7-HEC)on PC12 cell injury induced by hypobaric hypoxia.METHODS The rat adrenal pheochromocytoma cell line PC12 was cultured under low-pressure hypoxia(5%CO_(2),94%N2,1%O_(2),54004 Pa)to investigate the different concentrations of 7-HEC(100,10,1,0.1,0.01μmol/L)on the survival rate of hypoxic cells;the effects of 7-HEC(1μmol/L)on the contents of lactate dehydrogenase(LDH)and malondialdehyde(MDA),superoxide dismutase(SOD)activity,apoptotic rate,cell cycle,and the expressions of cleaved caspase-3,Bcl-2 and Bax were detected.RESULTS Compared with control group,the survival rate of cells in hypobaric hypoxia group was decreased significantly(P<0.01);10,1,0.1μmol/L 7-HEC could reverse the decrease of cell survival rate caused by hypobaric hypoxia(P<0.05 or P<0.01).Compared with control group,LDH content in supernatant,MDA content in cells,apoptotic rate,the proportion of cells at G1 stage and the protein expression of cleaved caspase-3 were increased significantly in hypobaric hypoxia group,while SOD activity in cells,the proportion of cells at S stage and G2 stage and Bcl-2/Bax ratio were decreased significantly(P<0.05 or P<0.01).Compared with hypobaric hypoxia group,the contents of LDH and MDA,apoptotic rate,the proportion of cells at G1 stage and the expression of cleaved caspase-3 in 7-HEC group were decreased significantly,while SOD activity,the proportion of cells at G2 stage and Bcl-2/Bax ratio were increased significantly(P<0.01).CONCLUSIONS 7-HEC can significantly increase the survival rate of hypobaric hypoxia cells,reduce the LDH content in supernatant,improve cell cycle arrest,and reduce the rate of apoptosis.Its improvement effects on hypobaric hypoxia cell injury may be related to the inhibition of caspase-3/Bax/Bcl-2 pathway activation.

关 键 词：7-羟乙基白杨素 PC12细胞 低压缺氧 细胞凋亡 caspase-3/Bax/Bcl-2通路 

分 类 号：R966[医药卫生—药理学]