塞络通通过激活Nrf2/HO-1信号通路改善OGD/R诱导脑微血管内皮细胞损伤  

Sailuotong improves OGD/R induced injury of brain microvascular endothelial cells by up-regulating Nrf2/HO-1 signaling pathway

作　　者：范晓迪[1] 姚明江[1] 李澎[1] 徐立[1] FAN Xiao-di;YAO Ming-jiang;LI Peng;XU Li(Beijing Key Lab of Pharmacology of Chinese Materia Medica,Institute of Basic Medical Sciences,Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]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,北京100091

出　　处：《中国药理学通报》2020年第7期1018-1023,共6页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金资助项目(No.7194314);国家自然科学基金资助项目(No.81873040);国家科技重大专项项目(No.2018ZX09737009)。

摘　　要：目的基于脑微血管内皮细胞保护,探讨塞络通(SLT)治疗脑缺血损伤的机制。方法培养人脑微血管内皮细胞株;SLT与细胞共孵育,CCK-8法测定细胞活力,确定药物安全浓度范围;建立细胞OGD/R模型,以SLT进行干预,CCK-8法测定细胞活性;检测细胞超氧化物歧化酶(SOD)活力,细胞还原型谷胱甘肽(GSH)含量,细胞上清液血红素加氧酶(HO-1)含量,细胞HO-1、Nrf2表达水平;最后加入Nrf2抑制剂,观察其对SLT治疗作用的影响,基于抗氧化、Nrf2/HO-1通路验证药物治疗机制。结果 OGD/R导致细胞活力、SOD活力、GSH含量明显下降,HO-1含量增加;SLT显著抑制细胞活性、SOD活力、GSH的下降,进一步增加HO-1含量,并上调Nrf2/HO-1蛋白的表达;塞络通的治疗作用被Nrf2抑制剂取消。结论 SLT通过激活Nrf2/HO-1信号通路发挥其对OGD/R诱导脑微血管内皮细胞损伤的保护作用。Aim To discuss the therapeutic mechanism of Sailuotong on cerebral ischemia injury based on the protection of microvascular endothelial cells.Methods The human brain microvascular endothelial cell strain was cultivated.Cell vitality was measured by cell counting Kit-8(CCK-8)in order to determine the range of drug safety in SLT and cell incubating.The OGD/R model was established to determine cell activity of the cells,the levels of superoxide dismutase(SOD),glutathione(GSH),heme oxygenase(HO-1)and the levels of Nrf2 and HO-1 expression by intervening SLT.Finally,the Nrf2 inhibitor was added to observe the effect of SLT therapy,which was based on the anti-oxidant and Nrf2/HO-1 pathway to verify the drug treatment mechanism.Results Cell viability,SOD,GSH levels were reduced and HO-1 levels were up-regulated in OGD/R induced hCMEC/D3.Treatment with SLT increased the cell viability,SOD,GSH and HO-1 levels.The expressions of Nrf2 and HO-1 were up-regulated obviously in SLT treatment.All the above indicated that ML385 completely reversed the protection effect of SLT.Conclusions SLT is demonstrated to protect human brain microvascular endothelial cell injury through the antioxidant action mediated by Nrf2/HO-1 signaling pathway.

关 键 词：核因子相关因子2 血红素加氧酶-1 脑微血管内皮细胞 氧葡萄糖剥夺/复氧 氧化应激损伤 塞络通 

分 类 号：R282.71[医药卫生—中药学] R322.12[医药卫生—中医学]