p38丝裂原活化蛋白激酶信号通路在炎性痛大鼠吗啡耐受形成中的作用  

Effects of p38 mitogen activated protein kinase pathway in inflammatory pain rats with morphine tolerance

作　　者：董莹 韩金玉 孙姗 赵洪伟 王国林[2] Dong Ying;Han Jinyu;Sun Shan;Zhao Hongwei;Wang Guolin(Department of Anesthesiology,Tianjin Medical University Institute and Hospital,National Clinical Research Center,Tianjin's Clinical Research Center for Cancer,Tianjin 300060;Department of Anesthesiology,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学肿瘤医院麻醉科,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,天津300060 [2]天津医科大学总医院麻醉科,天津30052

出　　处：《神经解剖学杂志》2020年第5期536-540,共5页Chinese Journal of Neuroanatomy

基　　金：天津自然科学基金(06YFJMJC08600)。

摘　　要：目的:探讨p38 MAPK抑制剂SB203580对炎性痛吗啡耐受大鼠背根神经节(DRG)辣椒素受体(VR1)及磷酸化辣椒素受体(p-VR1)表达的影响。方法:24只健康成年SD大鼠随机分为对照组(control)、吗啡处理组(morphine)和吗啡联合p38 MAPK抑制剂SB203580处理组(morphine+SB203580)。利用踝关节腔注射完全弗氏佐剂(CFA)的方法制备大鼠炎性痛模型,通过鞘内置管方法给予吗啡或者吗啡联合SB203580处理,通过热板法测定各组大鼠的缩足潜伏期(PWL),利用Western Blot检测各组大鼠DRG中VR1及p-VR1的表达。结果:与基础值比较,morphine+SB203580组给药前及给药4~7 d时大鼠的PWL缩短(P <0.05);与吗啡处理组比较,吗啡联合SB203580处理组给药4~7 d时PWL延长(P <0.05);与对照组比较,吗啡处理组和吗啡联合SB203580处理组大鼠DRG中VR1及p-VR1表达上调(P <0.05);与吗啡处理组比较,吗啡联合SB203580处理组大鼠DRG中p-VR1水平降低(P <0.05)。结论:p38 MAPK抑制剂SB203580能够抑制炎性痛大鼠吗啡耐受的形成,背根神经节处VR1表达及磷酸化与吗啡耐受有关,p38 MAPK信号传导通路参与了大鼠慢性吗啡耐受的形成。Objective: To investigate the change of expression of vanilloid receptor 1(VR1) and phospho-vanilloid receptor 1(p-VR1) in dorsal root ganglion in rats with chronic inflammatory pain-morphine tolerance.Methods: 24 healthy adult SD rats are between control and morphine treatment and between morphine and morphine combined with the P38 MAPK inhibitor SB203580.It is between morphine and SB203580.The rat model of inflammatory pain was prepared by injecting complete Freundell adjuvant(CFA) into the ankle cavity.Morphine or morphine combined with SB203580 was treated by the method of intrathecal sheath tube.The paw contraction incubation period(PWL) of each group was determined by hot plate method,and the expressions of VR1 and p-VR1 in DRG of each group were detected by Western Blot.Results: Compared with basline,it is estimated that SB203580 groups will achieve PWL reduction before administration and between 4 and 7 days after administration(P < 0.05);Compared with morphine treatment group,morphine combined with SB203580 treatment group received 4-7 days of PWL extension(P < 0.05);Compared with the control group,the expressions of VR1 and p-VR1 in DRG of morphine treated group and morphine combined with SB203580 group were up-regulated(P < 0.05);Compared with morphine treated group,morphine combined with SB203580 treated group reduced the p-VR1 level in DRG(P < 0.05).Conclusion: p38 MAPK inhibitor SB203580 can inhibit the formation of morphine tolerance in rats with inflammatory pain.The expression and phosphorylation of VR1 in dorsal root ganglia are related to morphine tolerance,and the p38 MAPK signaling pathway is involved in the formation of chronic morphine tolerance in rats.

关 键 词：P38 MAPK抑制剂 吗啡耐受 辣椒素受体 关节炎 大鼠 

分 类 号：R614[医药卫生—麻醉学]