Ⅱ型大麻受体激动剂JWH133对大鼠局灶性脑缺血—再灌注损伤的神经保护作用

Protective Effect of CB2 Agonist JWH133 on Cerebral Ischemia-Reperfusion Injury in Rats

目的探讨Ⅱ型大麻受体(CB2)激动剂JWH133预处理对大鼠局灶性脑缺血-再灌注损伤后作用的机制。方法将健康成年雄性SD大鼠40只随机分为假手术组、脑缺血-再灌注模型组(模型组)、JWH133给药组和溶剂对照组。用改良Zea Longa线栓法建模。Longa评分法评价神经功能,TTC染色法测定缺血侧脑组织及周围血清中白细胞介素(IL)-6和IL-1β水平,TUNEL免疫荧光染色检测大鼠神经元凋亡情况。结果 4组试验大鼠均不同程度出现神经行为功能异常,但JWH133给药组大鼠的神经行为功能恢复明显优于其他3组(P<0.05)。脑切片染色显示,3个手术组大鼠均出现供血区白色梗死灶,但JWH133给药组白色梗死灶较模型组和溶剂对照组缩小(P<0.05)。模型组大鼠脑组织及血清中IL-6、IL-1β水平较假手术组显著升高,JWH133给药组治疗后2种炎性因子水平均有不同程度降低,与溶剂对照组对比均有显著性差异(P<0.05)。TUNEL染色显示,假手术组几乎无凋亡细胞,模型组及溶剂对照组凋亡细胞数量显著增加,JWH133给药组凋亡神经细胞显著减少。结论 JWH133预处理通过抑制脑缺血-再灌注损伤过程发挥神经保护作用,其机制可能与降低IL-6、IL-1β水平及发挥抗凋亡作用有关,尚待进一步探讨。

Objective To investigate the effect of CB2 agonist JWH133 pretreatment on focal cerebral ischemia / reperfusion injury in rats and its underlying mechanism. Methods 40 healthy adult male SD rats were randomly divided into 4 groups（ n = 10）：sham opera- tion group,model group,JWH133 group and solvent control group. The modified ZeaLonga suture method was used to build the models with,theLonga score was used to evaluate the neurological function,the TFC staining methodwas used to determine the content of is- chemic brain tissue and peripheral serum IL-6 and IL-1β,and the TUNEL immunofluorescence stain method was used to detect the apoptosis of rat neurons. Results The rats in the four groups all had different degrees of abnormal neurological function. The JWH133 group was significantly better in the neurological recovery than the other 3 groups（P 〈 0.05）. Brain slice staining showed that all groups had white perforating artery infarct,but the infarctin the JWH133 group was smaller than the model group and control group （P 〈 0.05）. The levels of IL-6 and IL-1β in serum and brain tissue of rats in the model group were significantly higher than the sham operation group（ P 〈 0.05）,and the two inflammatory factors were reduced after treatment of JWH133（ P 〈 0.05）. TUNEL stain- ing showed that there were almost no apoptotic cells in the sham operation group,the number of model group and solvent control group apoptotic ceils was significantly increased, and the apoptotic neurons in JWH133 intervention group were significantly de- creased. Conclusion JWH133 preconditioning may play a neuroprotective role in cerebral ischemia-reperfusion injury,and its mecha- nism may be related to reducing the levels of IL- 6,IL-1β,and playing the role of antiapoptosis. The mechanism of the neuroprotec- tive effect of CB2 agonist JWH133 remains to be further explored.