基于TLR4/NF-κB信号通路研究右美托咪定对脑卒中后中枢痛大鼠的镇痛机制

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Abstract Objective To observe the analgesic effect of intraperitoneal injection of Dexmedetomidine on central pain (CPSP) after stroke in rats through TLR4/NF-κB signaling pathway. Methods Thirty SD rats were selected randomly from 90 SD rats for sham operation group, and the remaining 60 rats were modeled by injecting type Ⅳ collagenase into ventralis posterolateral nucleus (VPL). The thermal withdrawal latency (TWL) was measured three days after modeling. The rats with reduced TWL were divided into model group and intervention group by random number table method, with 30 rats in each group. The intervention group was intraperitoneal injected Dexmedetomidine 50 μg/kg for seven consecutive days and the model group was injected with the same amount of narmal saline. TWL values of rats were measured one day before modeling (T0), 10 d after modeling (T1), 17 d after modeling (T2), and 31 d after modeling (T3). Western blot was used to detect protein expression in VPL at T3. The changes of VPL microglia and neurons were observed by immunofluorescence. The release of inflammatory mediators in VPL was detected by enzyme-linked immunosorbent assay. Results In model group and intervention group, TWL at T1-T3 was lower than T0, TWL at T2-T3 was lower than T1, and TWL at T3 was lower than T2 (P ＜ 0.05). The TWL at T1-T3 in the model group was lower than that in the sham operation group, and the TWL at T1-T3 in the intervention group was higher than that in the sham operation group (P ＜ 0.05). Compared with sham operation group, the expression of TLR4 and pNF-κB in VPL of model group was significantly increased (P ＜ 0.05). Compared with model group, the expression of TLR4 and pNF-κB in VPL of intervention group was decreased (P ＜ 0.05). There was no significant difference in NF-κB expression in VPL among the three groups (P ＞ 0.05). Compared with sham operation group, the number of VPL neurons in model group decreased (P ＜ 0.05); compared with model group, there was no significant difference in the number of VPL neurons in the intervention group (P ＞ 0.05). The levels of IbA-1, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in VPL of model group were increased compared with that of sham operation group (P ＜ 0.05), while the levels of IBA-1 and inflammatory factors TNF-α, IL-1β, and IL-6 in VPL of intervention group were decreased compared with that in model group (P ＜ 0.05). Conclusion Dexmedetomidine treat the CPSP may inhibit the proliferation and activation of microglial cells and the progression of neuroinflammation through the TLR4/NF-κB signaling pathway.

Key words： TLR4/NF-κB signaling pathway TLR4/NF-κB signaling pathway Central post-stroke pain Dexmedetomidine Microglia Central sensitization

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	HUANG Dingli ZOU Wanyun ZHANG Ying LIU Qing

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HUANG Dingli ZOU Wanyun ZHANG Ying LIU Qing. Based on TLR4/NF-κB signaling pathway study the pain mechanism of Dexmedetomidine on central pain in rats after stroke[J]. 中国医药导报, 2022, 19(22): 30-33,38.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2022/V19/I22/30

[1] 谭娟，李晓敏，苟晨，等.经颅直流电刺激对脑卒中后中枢性疼痛患者的镇痛效果研究[J].川北医学院学报，2021， 36（6）：753-756.
[2] 赵庆祥，吴小娟，王德强，等.脑卒中后疼痛的诊疗进展[J].国际麻醉学与复苏杂志，2020，41（12）：1201-1205.
[3] 周静，袁大华，王玉凯，等.普瑞巴林在脑卒中后中枢神经痛治疗中的观察研究[J].中国医药科学，2021，11（10）：184-186，216.
[4] 田英瑞，王雪，薛冰华，等.慢性应激下脑内高糖诱导小鼠海马小胶质细胞M1型极化[J].营养学报，2022，44（1）：1-7.
[5] 高哲健祎，谢开宇，徐义勇，等.蛇床子素对骨癌痛大鼠的镇痛作用及对TLR4/NF-κB信号通路的影响[J].中医药导报，2022，28（1）：25-30.
[6] 姜爽，颜丽晖，夏蓉，等.阿片类药物所致痛觉敏化的神经炎症免疫机制[J].中国疼痛医学杂志，2021，27（11）：851-855.
[7] 曾学晴，杨彬，周鑫，等.右美托咪定通过抑制脊髓星形胶质细胞活化改善甲醛诱导的急性炎性痛[J].解剖学报，2021，52（5）：681-685.
[8] 肖凡，罗振中，卢俊，等.右美托咪定预给药对切口痛大鼠脊髓胶质细胞的影响[J].实用医学杂志，2018，34（7）：1111-1114.
[9] 赵义，彭祖菊，龙明锦，等.右美托咪定抑制脂多糖诱导N9小胶质细胞的炎症因子及凋亡[J].中国煤炭工业医学杂志，2019，22（6）：635-639.
[10] 张静婧，李姝睿，王琼，等.丁苯酞联合TLR4抗体鼓室给药小鼠梅尼埃病模型的实验研究[J].中华耳科学杂志，2022，20（1）：15-20.
[11] 李银霞，高敏，白雪，等.绿原酸通过抑制AMPA受体的突触表达缓解慢性炎性疼痛[J].中国药理学通报，2021， 37（9）：1251-1256.
[12] Shyu BC，He AB，Yu YH，et al. Tricyclic antidepressants and selective serotonin reuptake inhibitors but not anticonvulsants ameliorate pain，anxiety，and depression symptoms in an animal model of central post-stroke pain [J]. Mol Pain，2021，17：17448069211063351.
[13] Yeo J，Park S. Effect of dexmedetomidine on the development of mechanical allodynia and central sensitization in chronic post-ischemia pain rats [J]. J Pain Res，2018， 11：3025-3030.
[14] 吴磊，颜曼，邱春玉.鸡血藤醇提物对小鼠炎性痛的影响[J]，湖北科技学院学报（医学版），2019，33（6）：461-464.
[15] 肖鸿智.加巴喷丁联合度洛西汀治疗脑卒中后中枢性疼痛的临床疗效[J].临床合理用药杂志，2020，13（36）：37-39.
[16] 袁建容，龚泽辉，蒙利娇，等.脑卒中后中枢性疼痛的康复治疗研究进展[J].中国康复医学杂志，2022，37（1）：121-124.
[17] 原晓玲，杨发明，王维峰.普瑞巴林联合小剂量奥氮平对卒中后中枢痛的临床观察[J].中西医结合心脑血管病杂志，2018，16（12）：1757-1759.
[18] 陆晏精，赵中.慢性疼痛发病相关生物医学、心理学机制研究进展[J].山东医药，2021，61（3）：103-106.
[19] 张威，马保新.大麻素受体2型与疼痛的关系[J].福建医药杂志，2021，43（5）：125-126.
[20] 覃勤，夏天，李月发，等.枢经热疗对神经病理性疼痛模型大鼠的镇痛作用及机制[J].中国组织工程研究，2022， 26（26）：4199-4204.
[21] 邵帅，陈彦霖，地里热巴提·地力木拉提，等.麝香保心丸对小鼠缺血性脑卒中的保护作用及机制[J].复旦学报（医学版），2021，48（3）：292-299.
[22] Wongpun J，Chanmanee T，Tocharus C，et al. The effects of festidinol treatment on the D-galactose and aluminum chloride-induced Alzheimer-like pathology in mouse brain [J]. Phytomedicine，2022，98：153925.
[23] 罗莉，韩尊，冯瑞雪，等.小胶质细胞在缺血性脑卒中活化的常见信号通路[J].赣南医学院学报，2021，41（8）：844-850.
[24] 龚拯，韦慧君，栗俊，等.右美托咪定药理及其对器官保护作用的研究进展[J].中国临床新医学，2020，13（10）：1065-1069.
[25] 魏碧玉，李凌海，刘伟.右美托咪定对重要器官保护作用研究进展[J].转化医学杂志，2020，9（6）：384-387.