艾片防治给药对脑缺血再灌注模型大鼠的作用及机制  

Effects and Mechanisms of L-Borneolum on Prevention and Treatment of Cerebral Ischemia-Reperfusion Injury in Rats

作　　者：付尹 王立映 王建[1,2,3] 杨显娟 王佳俊 龚道银 肖琳萱[1,2,3] Fu Yin;Wang Liying;Wang Jian;Yang Xianjuan;Wang Jiajun;Gong Daoyin;Xiao Linxuan(College of Pharmacy,Chengdu University of TCM,Chengdu 611137;Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,Chengdu University of TCM,Chengdu 611137;State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,Chengdu 611137;Affiliated Hospital of Chengdu University of TCM,Chengdu 610075)

机构地区：[1]成都中医药大学药学院,成都611137 [2]成都中医药大学西南特色中药资源重点实验室,成都611137 [3]西南特色中药资源国家重点实验室,成都611137 [4]成都中医药大学附属医院,成都610075

出　　处：《中药药理与临床》2021年第4期101-105,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:81873023,81473371);成都中医药大学中药“性-效-用”理论与实践创新团(编号:CXTD2018004);成都中医药大学西南特色中药资源重点实验室开放研究基金资助项目(编号:2020XSGG025)。

摘　　要：目的:研究艾片对脑缺血再灌注损伤(CIRI)大鼠的脑保护作用及机制。方法:采用防治结合给药方式对线栓法制备的脑缺血再灌注模型大鼠进行干预,测量不同时间点(再灌注4 h、22.5 h、46.5 h和70.5 h)模型大鼠的体温,观察其体温变化;根据mNss评分法对模型大鼠不同时间点(与体温同步)神经功能进行评价;苏木精-伊红(Hematoxylin-eosin, HE)染色法观察模型大鼠缺血侧脑组织病理形态;酶联免疫吸附法检测模型大鼠血清中锰-超氧化物歧化酶(Mn-Superoxide dismutase, Mn-SOD)、活性氧(reactive oxygen species, ROS)及丙二醛(Malondialdehyde, MDA)的水平;蛋白质印记(Western blotting, Wb)法检测模型大鼠缺血侧皮层BCL-2相关X蛋白(BCL-2 Associated X Protein, BAX)蛋白表达。结果:与假手术对照组比较,模型对照组大鼠的体温及各时间点mNss评分均显著升高(P<0.01),溶剂模型组大鼠血清Mn-SOD水平显著降低,血清ROS、MDA含量及缺血侧皮层BAX蛋白表达水平均显著升高(P<0.01);与模型对照组比较,溶剂模型组大鼠各药效学指标无显著性差异;与溶剂模型组比较,艾片0.1、0.2 g/kg组均能显著降低再灌注22.5 h、46.5 h和70.5 h的mNss评分、ROS、 MDA含量及BAX蛋白表达水平,显著升高Mn-SOD水平(P<0.01),并明显改善皮层及海马CA1区病理损伤,艾片0.2 g/kg组还能明显降低体温、再灌注4 h的mNss评分(P<0.05或P<0.01)。结论:艾片可对脑缺血再灌注模型大鼠发挥脑保护作用,其潜在机制可能与抗氧化应激和凋亡有关。Objective:To investigate the protective effect and possible mechanism of L-borneolum against cerebral ischemia-reperfusion injury(CIRI) in rats. Methods: The CIRI rat model was established using Longa method and then intervened with drugs for protection and treatment. The body temperature of CIRI rats was measured at different time points(4 h, 22.5 h, 46.5 h, and 70.5 h after reperfusion) for observing the changes. mNss scoring of CIRI rats was conducted at various time points(synchronizing with body temperature measurement). The pathological features of ischemic brain tissue were detected by hematoxylin-eosin(HE) staining. The levels of Mn-superoxide dismutase(Mn-SOD), reactive oxygen species(ROS), and malondialdehyde(MDA) were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the level of Bcl-2 associated X protein(BAX) was assayed by Western blotting(Wb). Results: Compared with the sham operation group, the model group exhibited significantly increased body temperature and mNss score at each time point(P<0.01). The serum Mn-SOD level in the solvent model group was significantly lowered, while the levels of ROS and MDA in serum and BAX in the ischemic cortex were significantly elevated(P<0.01). The comparison between the model group and the solvent model group revealed no significant differences in pharmacodynamic indexes. Compared with the solvent model group, L-borneolum at both 0.1 g/kg and 0.2 g/kg significantly reduced the mNss score and ROS, MDA, and Bax levels after reperfusion for 22.5 h, 46.5 h, and 70.5 h, increased the level of Mn-SOD(P<0.01), and relieved the pathological damages in the cortex and hippocampus CA1 area. At the same time, L-borneolum at 0.2 g/kg also reduced body temperature(P<0.05) and mNss score after reperfusion for 4 h(P<0.05 or P<0.01). Conclusion: L-borneolum protects CIRI rats away from brain damage possibly by inhibiting oxidative stress and apoptosis.

关 键 词：艾片 脑缺血再灌注 神经功能 抗氧化 抗凋亡 

分 类 号：R285.5[医药卫生—中药学]