芍药苷激活2型大麻素受体保护脑缺血再灌注大鼠海马神经元

Protective effect of paeoniflorin on the hippocampus in rats with cerebral ischemiareperfusion through activating cannabinoid receptor 2

目的探究芍药苷通过激活2型大麻素受体(CBR2)对脑缺血再灌注大鼠神经的保护作用。方法 144只雄性SD大鼠随机分为假手术组、模型组、溶媒组、10mg/kg芍药苷组、40mg/kg芍药苷组、CBR2选择性拮抗剂3mg/kg AM630组、40mg/kg芍药苷联合3mg/kg AM630组、CBR2选择性激动剂3mg/kg HU308处理组。线栓法制作大鼠局灶性脑缺血/再灌注模型。观察芍药苷对神经功能缺损评分、梗塞体积、脑水肿的影响;采用HE染色观察脑组织病理形态学改变;采用免疫组织化学染色法观察芍药苷对海马区环氧合酶2(COX-2)和caspase-3表达的影响。结果芍药苷能显著改善脑缺血大鼠神经功能评分,降低梗塞体积及缺血侧脑含水量,减轻脑组织病变,抑制海马区caspase-3和COX-2的表达;但预先注射AM630可显著拮抗芍药苷的脑神经保护作用。结论 CBR2可能参与芍药苷对脑缺血再灌注大鼠海马神经元的保护作用。

Objective To investigate the protective effect of paeoniflorin on hippocampal neurons in rats subjected to cerebral ischemia and reperfusion through activating cannabinoid receptor 2（CBR2）.Methods A total of 144 male SD rats were randomly divided into sham-operation group,cerebral ischemia-reperfusion model group,menstruum group,10 and 40mg / kg paeoniflorin groups,3mg / kg CBR2 selective antagonist AM630 group,40mg / kg paeoniflorin combined with 3mg / kg AM630 group,and 3mg / kg CBR2 selective agonist HU308 treatment group.Focal cerebral ischemia-reperfusion models were made by inserting a monofilament suture into internal carotid artery.The neurological scores,infarction volume and cerebral edema were detected careful y to find out the effect of paeoniflorin on neurons.Pathological changes were observed by HE staining.The expressions of caspase-3 and cyclooxygenase 2（COX-2） in hippocampal CA1 region were determined by immunohistochemistry.Results Paeoniflorin significantly decreased the neurological scores,infarction volume and cerebral edema.In addition,paeoniflorin relieved the pathological changes and inhibited the expressions of caspase-3 and COX-2 in hippocampus CA1 area.But injecting AM630 in advance obviously counteracted the neuroprotective effect of paeoniflorin.Conclusion CBR2 may participate in the protective effect of paeoniflorin on hippocampal neurons of cerebral ischemia-reperfusion rat models.