CB1拮抗剂利莫那班联合CB2激动剂JWH133对脑缺血再灌注病理损伤保护作用的研究

发布时间：2018-06-08 02:32

本文选题：利莫那班 + JWH　；参考：《中国现代医学杂志》2015年10期

【摘要】：目的探讨大麻系统(ECS)药物CB1拮抗剂利莫那班联合CB2激动剂JWH133预处理对大鼠脑缺血再灌注损伤的神经保护作用机制。方法将健康成年雄性SD大鼠随机分为假手术组、模型组、JWH133组和LHGY组(利莫那班+JWH133)。造模前1 h用二甲基亚砜(DMSO)溶解药物,预处理腹腔注射给药;其他两组注射等体积生理盐水,改良ZEA-LONGA线栓法建立大鼠右脑中动脉缺血再灌注模型。采用Longa评分法进行神经功能评分,TTC染色测量脑梗死体积,测定缺血侧脑组织及周围血清中和白细胞介素-6(IL-6)和白细胞介素-10(IL-10)含量,比色法检测诱导型一氧化氮合酶(i NOS)活性的表达。结果模型组、JWH133组和LHGY组均出现不同程度的神经行为功能异常,两组神经行为功能恢复明显好于其他两组(P0.05),LHGY组表现略优于JWH133组(P0.05)。其中,脑切片TTC染色显示JWH133组和LHGY组均较模型组白色梗死灶缩小(P0.05),后者梗死面积程度小于前者(P0.05)。模型组大鼠脑组织及血清中IL-6含量比假手术组含量有较显著的升高,IL-10则相反;而JWH133组和LHGY组治疗后两种炎性因子呈现不同程度的反相变化(P0.05)。与假手术组相比,模型组脑组织中i NOS活性明显升高;JWH133组和LHGY组脑组织中i NOS活力均明显降低(P0.05)。结论 JWH133组和LHGY组预处理后通过抑制脑缺血再灌注损伤过程中的炎性反应而发挥神经保护作用,其机制可能与调节IL-6、IL-10和i NOS等因子水平有关。而CB1拮抗剂利莫那班联合CB2激动剂JWH133给药方案产生一定程度的叠加效果,这也提示ECS对脑缺血再灌注损伤产生神经保护作用机制尚待进一步探讨。
[Abstract]:Objective to investigate the neuroprotective mechanism of CB1 antagonist rimonaban combined with CB2 agonist JWH133 on cerebral ischemia-reperfusion injury in rats. Methods healthy adult male Sprague-Dawley rats were randomly divided into sham-operated group, model group (JWH133) and LHGY group (Rimonaban JWH133). One hour before the model was made, dimethyl sulfoxide (DMSO) was used to dissolve the drug, and the other two groups were injected intraperitoneally with the same volume of normal saline, and the model of right middle cerebral artery ischemia reperfusion was established by modified ZEA-LONGA method. The volume of cerebral infarction was measured by using Longa score and TTC staining. The contents of interleukin-6 (IL-6) and interleukin-10 (IL-10) in and around the ischemic cerebral tissue were measured. The activity of inducible nitric oxide synthase (iNOS) was detected by colorimetry. Results there were different degrees of neurobehavioral dysfunction in JWH133 group and LHGY group, and the recovery of neurobehavioral function in both groups was better than that in the other two groups (P0.05 and LHGY), which was slightly better than that in JWH133 group. TTC staining showed that both JWH133 group and LHGY group were smaller than the model group in white infarct size (P0.05), and the infarct area of the latter group was smaller than that of the former group (P0.05). The level of IL-6 in the brain and serum of the model group was significantly higher than that of the sham operation group, while the level of IL-10 in the JWH133 group and the LHGY group was significantly higher than that in the sham operation group, while the two inflammatory factors in the JWH133 group and the LHGY group showed different degrees of reverse changes after treatment (P 0.05). Compared with the sham-operated group, the activity of iNOS in the brain tissue of the model group was significantly higher than that of the JWH133 group and the LHGY group, and the activity of iNOS in the brain tissue of the model group was significantly lower than that of the control group. Conclusion the neuroprotective effect of JWH133 and LHGY groups may be related to the regulation of IL-6 / IL-10 and iNOS levels by inhibiting the inflammatory response during cerebral ischemia-reperfusion injury in JWH133 and LHGY groups. The combination of CB1 antagonist rimonaban and CB2 agonist JWH133 has a superposition effect to some extent, which suggests that the neuroprotective mechanism of ECS on cerebral ischemia-reperfusion injury remains to be further explored.
【作者单位】：重庆三峡医药高等专科学校;重庆医科大学;重庆市妇幼保健院;
【基金】：重庆市基础与前沿研究计划项目(No:cstc2014jcyj A10049) 2014年6月重庆市高等学校青年骨干教师资助计划重庆市卫生局医学科研项目(No:20121096)
【分类号】：R965

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