黄芩素对缺氧致大鼠皮质神经元细胞损伤的保护作用及机制  

Protective effect and mechanism of baicalein on hypoxia-induced cortical neuron injury in rats

作　　者：张冬梅 张洁 石志群 张朋朋 谭宏强 马慧萍 ZHANG Dongmei;ZHANG Jie;SHI Zhiqun;ZHANG Pengpeng;TAN Hongqiang;MA Huiping(Dept.ofPharmacy,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12期1431-1436,共6页China Pharmacy

基　　金：甘肃省科技计划项目(No.22JR11RA014);甘肃省卫生健康行业科研项目(No.GSWSKY2022-46);第九四〇医院院内科研项目(No.2021yxky046,No.2022yxky004)。

摘　　要：目的探讨黄芩素对缺氧致大鼠皮质神经元细胞损伤的保护作用及可能机制。方法以大鼠皮质神经元RN-C细胞为研究对象,以缺氧条件(5%CO_(2)、94%N2、1%O_(2))培养24 h,考察不同浓度黄芩素(0.01、0.1、1、10、100μmol/L)对缺氧RN-C细胞存活率的影响,并检测黄芩素(浓度为0.1μmol/L)对缺氧细胞的乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,细胞迁移率、凋亡率和细胞周期,以及对缺氧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,缺氧组细胞的存活率显著降低(P<0.01);0.01、0.1、1μmol/L黄芩素可以逆转缺氧导致的细胞存活率降低(P<0.05或P<0.01)。划痕实验显示,黄芩素可显著升高缺氧RN-C细胞的迁移率(P<0.01)。与对照组比较,缺氧组细胞上清液中LDH活性、细胞中MDA含量、凋亡率和G1期细胞比例显著增加,SOD活性、G2+S期细胞比例显著降低(P<0.01);细胞中cleaved caspase-3蛋白的表达量显著上升,Bcl-2/Bax比值均显著下降(P<0.05或P<0.01)。与缺氧组比较,黄芩素组细胞显著逆转了上述指标(P<0.01)。结论黄芩素能促进缺氧条件下大鼠皮质神经元细胞的增殖和迁移,改善缺氧诱导的细胞凋亡和细胞周期阻滞,降低上清液中LDH活性,降低细胞脂质过氧化水平,提高抗氧化水平;其机制可能与调控caspase-3/Bax/Bcl-2通路有关。OBJECTIVE To explore the protective effect and possible mechanism of baicalein on hypoxia-induced cortical neuron injury in rats.METHODS The cortical neurons of rats(RN-C cells)were studied and cultured under hypoxic conditions(5%CO_(2),94%N2,1%O_(2))for 24 hours;the effects of different concentrations of baicalein(0.01,0.1,1,10,100μmol/L)on the survival rate of hypoxic RN-C cells were investigated;the effects of baicalein(0.1μmol/L)on the activities of lactate dehydrogenase(LDH)and superoxide dismutase(SOD),the content of malondialdehyde(MDA),migration rate,apoptotic rate,cell cycle and the expressions of cleaved caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2 X protein(Bax)were all detected.RESULTS Compared with control group,the survival rate of cells in the hypoxia group was significantly reduced(P<0.01);0.01,0.1 and 1μmol/L baicalein could reverse survival rate of hypoxia-induced cortical neurons(P<0.05 or P<0.01).Scratch experiments showed that baicalein significantly increased the migration rate of hypoxic RN-C cells(P<0.01).Compared with control group,the activity of LDH in the supernatant and the content of MDA in the cells,apoptotic rate and the proportion of cells in G1 phase,were significantly increased in the hypoxia group,while SOD activity and the proportion of cells in G2+S phase was decreased significantly(P<0.01).The protein expressions of cleaved caspase-3 were increased significantly,while the ratio of Bcl-2/Bax in cells was significantly reduced(P<0.05 or P<0.01).Compared with hypoxia group,the above indexes were all reversed significantly in baicalein group(P<0.01).CONCLUSIONS Baicalein can promote the proliferation and migration of cortical neurons,improve hypoxia-induced cell apoptosis and cell cycle distribution,decrease the activity of LDH in supernatant and the level of cellular lipid peroxidation,and improve antioxidant levels.Its mechanism may be related to regulating the caspase-3/Bax/Bcl-2 pathway.

关 键 词：黄芩素 大鼠皮质神经元细胞 缺氧 神经保护 caspase-3/Bax/Bcl-2 

分 类 号：R965[医药卫生—药理学]