首页|黄芩苷通过调控人脑星形胶质细胞上TRPV4/AQP4改善OGD/R所致的细胞水肿

黄芩苷通过调控人脑星形胶质细胞上TRPV4/AQP4改善OGD/R所致的细胞水肿

扫码查看
目的:研究黄芩苷(BA)对氧糖剥夺(OGD/R)诱导损伤的人脑星形胶质细胞SVGp12的影响,从抑制钙离子内流和细胞水肿的角度,调控离子通道瞬时受体电位香草素受体4型通道蛋白(TRPV4)和水通道蛋白4(AQP4).方法:首先BA在SVGp12细胞上的安全用药浓度进行筛选,其次筛选OGD/R细胞模型,选用OGD/R(4 h/2 h)的方法模拟细胞在脑中缺血缺氧的环境,将分组设定为正常组、Model组、BA组(5 µ mol/L),并加入TRPV4抑制剂HC067047和激动剂GSK1016790A进行对照.用吸光度法测定了细胞活力,ELISA法测定细胞乳酸脱氢酶(LDH)渗透率,Western Blot法观察TRPV4和AQP4的表达,流式细胞术测定细胞内Ca2+浓度.结果:BA在12.5 µmol/L及更低的浓度范围内对正常培养的SVGp12细胞活力不产生影响;在OGD/R(4h/2h)的条件下,SVGp12细胞的OD值降低约50%(P<0.01);OGD/R诱导损伤后,BA的浓度为5 µmol/L时细胞活力值最高(P<0.01);BA能够改善GSK1016790A诱导后的SVGp12细胞的活力(P<0.05);BA能降低SVGp12细胞的LDH渗透率(P<0.05);BA能够抑制TRPV4和AQP4的表达(P<0.05);BA能够降低SVGp12细胞内Ca2+浓度(P<0.01).结论:BA对OGD/R诱导的SVGp12细胞具有保护作用,可能是通过抑制OGD/R后TRPV4和AQP4通道蛋白的上调,从而减少Ca2+内流并抑制细胞肿胀.
Baicalin improves cell edema caused by OGD/R by regulating TRPV4/AQP4 on human brain astrocytes
Objective:To investigate the effects of Baicalin(BA)on human astrocyte SVGp12 with oxygen-glucose depriration/reperfusion(OGD/R)-induced injury,to regulate ion channel transient receptor potential vanilloid 4(TRPV4)and aquaporin 4(AQP4)from the perspective of inhibiting calcium influx and cell edema.Methods:The safe drug concentration of BA on SVGp12 cells and the OGD/R cell model were screened.OGD/R(4 h/2 h)method was used to simulate the environment of ischemia and hypoxia in the brain,and the groups were set into Control group,Model group,and BA group(5 μmol/L).At the same time,TRPV4 inhibitor HC067047 and agonist GSK1016790A were added.The cell viability was determined by absorbance,the permeability of lactate dehydrogenase(LDH)by ELISA,the expression of TRPV4 and AQP4 by Western Blot and the concentration of Ca2+by flow cytometry.Results:BA had no effect on the viability of SVGp12 cells in the concentration range of 12.5 μmol/L and lower.Under the condition of OGD/R(4 h/2 h),the OD value of SVGp12 cells decreased by about 50%(P<0.01).After OGD/R induced injury,the cell viability was the highest when BA concentration was 5 μmol/L(P<0.01).BA could improve the activity of SVGp12 cells induced by GSK1016790A(P<0.05).BA decreased LDH permeability of SVGp12 cells(P<0.05).BA could inhibit the expression of TRPV4 and AQP4(P<0.05).BA could decrease the Ca2+concentration in SVGp12 cells(P<0.01).Conclusion:BA has a protective effect on OGD/R-induced SVGp12 cells,possibly by inhibiting the up-regulation of TRPV4 channel protein and AQP4 channel protein after OGD/R,thereby reducing Ca2+influx and inhibiting cell swelling.

AstrocytesBaicalinBrain edemaCellular edemaTransient receptor potential vanilloid 4(TRPV4)Aquaporin 4(AQP4)

郑晓宇、张业昊、宋文婷、丁昭、黄子珊、刘建勋

展开 >

中国中医科学院西苑医院基础医学研究所,中药药理北京市重点实验室,国家中医心血管疾病临床医学研究中心,北京 100091

广东药科大学中医药研究院,广州 511436

星形胶质细胞 黄芩苷 脑水肿 细胞水肿 TRPV4 水通道蛋白4

国家自然科学基金重点项目

82030124

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(5)