黄芩苷通过抑制星形胶质细胞TRPV4和AQP4治疗脑缺血再灌注引起的大鼠脑水肿  

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes

作　　者：郑晓宇[1,2] 宋文婷 张业昊[2] 曹慧 刘建勋 ZHENG Xiao-yu;SONG Wen-ting;ZHANG Ye-hao;CAO Hui;LIU Jian-xun(Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Key Laboratory of Pharmacology of Chinese Materia Medica,Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院,西苑医院,基础医学研究所,北京市中药药理重点实验室,北京100091

出　　处：《中国中药杂志》2022年第4期1031-1038,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金重点项目(8203000944)。

摘　　要：该文旨在研究黄芩苷对脑缺血再灌注损伤所引起的脑水肿大鼠的药效学作用及作用机制,并从抑制星形胶质细胞肿胀的角度探讨治疗脑缺血再灌注损伤和脑水肿的有关机制,对相关中药治疗脑缺血疾病具有借鉴意义。实验中采用大脑中动脉闭塞法(线栓法)制作大鼠脑缺血模型,将大鼠随机分为正常组、模型组、黄芩苷高剂量(20 mg·kg^(-1))组和黄芩苷低剂量(10 mg·kg^(-1))组,分别测定大鼠脑缺血后6、24 h的神经行为学、脑指数、脑含水量、脑梗死面积,大脑切片后采用苏木素-伊红(hematoxylin-eosin,HE)染色观察黄芩苷对脑皮层组织病理形态的影响,ELISA法测定脑组织中总谷胱甘肽(L-glutathione,GSH)和谷氨酸(glutamic acid,Glu)的含量,免疫印迹法(Western blot)测定脑组织中胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、水通道蛋白4(aquaporin-4,AQP4)、瞬时受体电位香草素受体4型通道(transient receptor potential vanilloid receptor 4,TRPV4)的含量,免疫组织化学染色法观察GFAP的表达情况,在机制探讨过程中采用黄芩苷低剂量组为给药组。实验结果显示,模型组大鼠的神经行为学评分(脑缺血6、24 h)、脑含水量和脑梗死面积均显著增加,黄芩苷高、低剂量均可降低大鼠的神经行为学评分、脑含水量和脑梗死面积;模型组大鼠脑组织中GSH的含量显著降低,Glu的含量显著增加,黄芩苷低剂量组可明显增加GSH的含量并降低Glu的含量;免疫组织化学染色可见模型组GFAP表达明显增加,星形胶质细胞肿胀并增殖,黄芩苷低剂量组可显著改善此情况;免疫印迹法结果显示,模型组大鼠脑皮层中GFAP、TRPV4、AQP4的表达均明显增加,黄芩苷低剂量组可显著降低它们的表达。病理学可见模型组大鼠大脑皮层结构损伤严重,黄芩苷低剂量组可明显改善皮层区病理损伤。以上结果表明,黄芩苷可有效改善大鼠脑缺血再灌注损伤所This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling,which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine.To be specific,middle cerebral artery occlusion(suture method)was used to induce cerebral ischemia in rats.Rats were randomized into normal group,model group,high-dose baicalin(20 mg·kg^(-1))group,and low-dose baicalin(10 mg·kg^(-1))group.The neurobehavior,brain index,brain water content,and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia.Brain slices were stained with hematoxylin and eosin(HE)for the observation of pathological morphology of cerebral cortex after baicalin treatment.Enzyme-linked immunosorbent assay(ELISA)was employed to determine the content of total L-glutathione(GSH)and glutamic acid(Glu)in brain tissue,Western blot to measure the content of glial fibrillary acidic protein(GFAP),aquaporin-4(AQP4),and transient receptor potential vanilloid type 4(TRPV4),and immunohistochemical staining to observe the expression of GFAP.The low-dose baicalin was used for exploring the mechanism.The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia),brain water content,and cerebral infarction area of the model group were increased,and both high-dose and low-dose baicalin can lower the above three indexes.The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group.Low-dose baicalin can elevate the content of GSH and lower the content of Glu.According to the immunohistochemical staining result,the model group demonstrated the increase in GFAP expression,and swelling and proliferation of astrocytes,and the low-dose baicalin can significantly improve this situation.The results of Western blot showed that the expression of GFAP,TRPV4,and AQP4 in the cerebral cortex of the model group inc

关 键 词：黄芩苷 星形胶质细胞 脑缺血 GFAP AQP4 TRPV4 

分 类 号：R285.5[医药卫生—中药学]