火麻仁油及大麻二酚对抑郁模型小鼠行为及炎症反应的影响

Effects of Hemp Seed Oil and Cannabidiol on Behavior and Inflammation in Depression Model Mice

目的:探究火麻仁油及大麻二酚(Cannabidiol,CBD)对慢性不可预测的轻度应激(Chronic unpredictable mild stress,CUMS)模型小鼠行为学及炎症因子的影响。方法:将50只雄性C57BL/6小鼠随机分成5组:空白组、模型组、火麻仁油组(3 mL/kg)、CBD低剂量组(15 mg/kg)、CBD高剂量组(30 mg/kg),试验周期8周,测定小鼠抑郁、焦虑、学习认知能力及炎症因子(肿瘤坏死因子(TNF-α)、白细胞介素-1(IL-1β)和诱导NOS(iNos))的mRNA表达及小胶质细胞的离子化的钙结合衔接分子1(IBA-1)的蛋白表达。结果:与空白组相比,模型组在抑郁和焦虑行为及学习和认知功能有显著差异(P<0.05;P<0.01);与模型组相比,CBD剂量组均显著改善模型小鼠的抑郁焦虑行为并提高了学习认知功能(P<0.05;P<0.01),火麻仁油组显著改善小鼠的蔗糖偏好指数和新物体识别能力(P<0.05)。与空白组相比,模型组小鼠的皮层和海马组织中TNF-α、IL-1β和iNos mRNA表达量显著升高(P<0.05;P<0.01);与模型组相比,CBD剂量组的皮层和海马TNF-α、IL-1β和iNos mRNA表达量均显著降低(P<0.05;P<0.01);火麻仁油组皮层、海马TNF-α和iNos无显著性差异(P>0.05)。免疫组化结果显示,火麻仁油和CBD均抑制炎症介质小胶质细胞的离子化的钙结合衔接分子1(IBA-1)的表达。结论:CUMS小鼠建模成功,火麻仁油能够提高小鼠的抑郁行为及认知能力,并且降低IL-1β表达,CBD可改善小鼠的焦虑症状、提升学习和认知功能,抑制脑组织皮层和海马的炎症反应,从而证明火麻仁油和CBD对CUMS模型小鼠具有一定的作用。

Objective:To explore the effects of hemp seed oil and Cannabidiol(CBD)on the behavior and inflammatory factors of chronic unpredictable mild stress(CUMS)mice.Methods:50 male C57BL/6 mice were randomly divided into 5 groups:Blank group,model group,hemp seed oil group(3 mL/kg),CBD low-dose(15 mg/kg),CBD high-dose group(30 mg/kg),and gavage was continued for 8 weeks.The expression of depression,anxiety,learning and cognitive ability and inflammatory factors(tumor necrosis factor(TNF-α),interleukin-1(IL-1β)and induced NOS(iNos))were measured in mice.Results:Compared with the blank group,the model group had significant differences in depression and anxiety behavior and learning and cognitive functions(P<0.05;P<0.01);compared with the model group,the CBD dose group significantly improved the model mice from the depressive and anxious behavior of mice to the cognitive function of learning(P<0.05;P<0.01);besides,the hemp seed oil group significantly improved the sucrose preference index and new object recognition ability in mice(P<0.05).Compared with the blank group,the expression of TNF-α,IL-1βand iNos mRNA in the cortex and hippocampus of the model group significantly increased(P<0.05;P<0.01);compared with the model group,CBD dose groups showed that the expression of TNF-α,IL-1βand iNos mRNA in the cortex and hippocampus significantly decreased(P<0.05;P<0.01);There was no significant difference in TNF-αand iNos in cortex and hippocampus of the hemp seed oil group(P>0.05).The results of immunohistochemistry showed that hemp seed oil and CBD both inhibited the expression of ionized calcium-binding adaptor molecule 1(IBA-1)of inflammatory mediator microglia.Conclusion:CUMS mice are successfully modeled.Hemp oil can partially improve the depressive behavior and cognitive ability of mice and reduce the expression of IL-1β.The CBD can improve the anxiety symptoms of mice,increase learning and cognitive functions,and inhibit the cortex and hippocampus of brain tissue.The inflammatory response of hemp seed oil and CBD has a certain effect on CUMS model mice.