大麻素Ⅱ型受体对LPS诱导小鼠黑质区COX-2和iNOS基因表达的影响  

EFFECT OF CANNABINOID TYPEⅡRECEPTORS ON LIPOPOLYSACCHARIDE-INDUCED GENE EXPRESSION OF CYCLOO-XYGENASE-2 AND INDUCIBLE NITRIC OXIDE SYNTHASE IN THE SUBSTANTIA NIGRA OF MICE

作　　者：王炳超[1] 孙琳[1] 朱天立 马泽刚[1] WANG Bingchao;SUN Lin;ZHU Tianli;MA Zegang(Department of Physiology,School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院生理学教研室,山东青岛266071

出　　处：《青岛大学学报（医学版）》2023年第3期371-374,共4页Journal of Qingdao University(Medical Sciences)

基　　金：山东省重点研发计划资助项目(2019GSF108095)。

摘　　要：目的探索大麻素Ⅱ型(CB2)受体对脂多糖(LPS)诱导小鼠黑质(SN)区炎症反应的作用。方法将18只8周龄雄性野生型(WT)C57BL/6小鼠随机分为WT对照组、WT LPS组和WT LPS+JWH133(CB2受体激动剂)组,12只8周龄雄性CB2受体敲除(CB2-KO)C57BL/6小鼠随机分为CB2-KO对照组和CB2-KO LPS组。对照组小鼠单次双侧SN立体定位注射生理盐水,其余各组小鼠注射等体积的LPS,然后连续腹腔注射JWH133或生理盐水14 d。应用实时荧光定量PCR技术检测各组小鼠SN中环氧化酶2(COX-2)和诱导型一氧化氮合酶(iNOS)基因的表达。结果与WT对照组相比,WT LPS组小鼠SN区COX-2和iNOS基因表达水平升高,差异有统计学意义(F=20.9、21.4,q=5.536、5.518,P<0.01);JWH133能明显抑制LPS诱导的COX-2和iNOS基因表达上调(q=5.170、4.553,P<0.05);与WT LPS组相比,CB2-KO LPS组小鼠COX-2和iNOS基因表达明显上调,差异有统计学意义(q=4.150、5.496,P<0.05)。结论激活CB2受体能够抑制LPS诱导小鼠SN区COX-2和iNOS基因的表达,缺失CB2受体能够促进LPS诱导小鼠SN区COX-2和iNOS基因的表达。Objective To investigate the effect of cannabinoid receptor-2(CB2)on lipopolysaccharide(LPS)-induced inflammatory response in the substantia nigra(SN)of mice.Methods A total of 18 male C57BL/6 wild-type(WT)mice,aged 8 weeks,were randomly divided into WT control group,WT LPS group,and WT LPS+JWH133(a CB2 receptor agonist)group,and 12 male CB2 receptor-knockout(CB2-KO)C57BL/6 mice were randomly divided into CB2-KO control group and CB2-KO LPS group.The mice in the control group received a single stereotactic injection of normal saline into the bilateral SN,and those in the other groups were injected with an equal volume of LPS,followed by the intraperitoneal injection of JWH133 or normal saline for 14 consecutive days.Quantitative real-time PCR was used to measure the mRNA expression levels of cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in the SN.Results Compared with the WT control group,the WT LPS group had significant increases in the mRNA expression levels of COX-2 and iNOS in the SN(F=20.9,21.4;q=5.536,5.518;P<0.01).JWH133 significantly inhibited the upregulated mRNA expression of COX-2 and iNOS induced by LPS(q=5.170,4.553;P<0.05).Compared with the WT LPS group,the CB2-KO LPS group had significant increases in the mRNA expression levels of COX-2 and iNOS(q=4.150,5.496;P<0.05).Conclusion Activation of CB2 receptor can inhibit LPS-induced mRNA expression of COX-2 and iNOS in the SN of mice,while deletion of CB2 receptor can promote LPS-induced mRNA expression of COX-2 and iNOS.

关 键 词：受体 大麻酚 CB2 脂多糖类 炎症 环氧化酶2 一氧化氮合酶 

分 类 号：R338.2[医药卫生—人体生理学]