[1]梁莹莹,王 欣,刘 芹,等.化合物DXL-A-22抗神经病理性疼痛作用及机制研究[J].中国药理学通报,2019,(10):1357-1363.[doi:10.3969/j.issn.1001-1978.2019.10.007]
 LIANG Ying-ying,WANG Xin,LIU Qin,et al.Anti-neuropathic pain effect of compound DXL-A-22[J].Chinese Pharmacological Bulletin,2019,(10):1357-1363.[doi:10.3969/j.issn.1001-1978.2019.10.007]
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化合物DXL-A-22抗神经病理性疼痛作用及机制研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年10期
页码:
1357-1363
栏目:
论著
出版日期:
2019-09-15

文章信息/Info

Title:
Anti-neuropathic pain effect of compound DXL-A-22
文章编号:
1001-1978(2019)10-1357-07
作者:
梁莹莹1王 欣2刘 芹1王 丁1杜小雷2李润涛2蒋益民3叶 加1
北京大学 1.药学院分子与细胞药理学系、 2.药学院化学生物学系、 3.医药卫生分析中心,北京 100191
Author(s):
LIANG Ying-ying1WANG Xin2LIU Qin1WANG Ding1DU Xiao-lei2LI Run-tao2JIANG Yi-min3YE Jia1
1.Dept of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences; 2.Dept of Chemical Biology,School of Pharmaceutical Sciences; 3.Dept of Medical and Healthy Analysis Center,Peking University,Beijing 100191,China
关键词:
螺环哌嗪季铵盐化合物DXL-A-22 抗神经病理性疼痛 CCI CaMKⅡα/CREB信号通路 JAK2/STAT3信号通路 TNF-α c-Fos
Keywords:
spirocyclopiperazinium salt compound DXL-A-22 anti-neuropathic pain CCI CaMKⅡα/CREB signaling pathway JAK2/STAT3 signaling pathway TNF-α c-Fos
分类号:
R-332; R322.81; R322.85; R342.2; R441.1; R741.02; R916.4
DOI:
10.3969/j.issn.1001-1978.2019.10.007
文献标志码:
A
摘要:
目的 研究螺环哌嗪季铵盐化合物DXL-A-22抗神经病理性疼痛作用及机制。方法 以坐骨神经慢性压迫性损伤(CCI)模型评价DXL-A-22的抗神经病理性疼痛作用; Western blot和qPCR技术研究DXL-A-22的作用机制; 极限实验评价DXL-A-22的急性毒性。结果 与溶媒组比较,DXL-A-22(2、 1、 0.5 mg·kg-1,i.g.)剂量依赖性提高CCI大鼠机械刺激缩足反应阈值和热刺激缩足潜伏期(P<0.05,P<0.01),术后d 7痛阈提高率分别为108%、86%和71%,最大镇痛百分率分别为77%、56%和43%; DXL-A-22(2 mg·kg-1)明显降低背根神经节(DRG)p-CaMKⅡα、p-CREB,p-JAK2、p-STAT3蛋白表达,以及TNF-α、c-Fos mRNA表达(P<0.05,P<0.01),抑制率分别为37%、48%、35%、58%、39%和32%; 明显降低脊髓TNF-α、c-Fos mRNA表达(P<0.01),抑制率分别为47%和72%; 无明显毒性反应。结论 螺环哌嗪季铵盐化合物DXL-A-22能明显抑制大鼠坐骨神经慢性压迫性损伤引起的神经病理性疼痛,无明显毒性,其机制可能与抑制DRG CaMKⅡα/CREB和JAK2/STAT3信号通路,降低DRG及脊髓TNF-α、c-Fos mRNA表达相关。
Abstract:
Aim To investigate the anti-neuropathic pain effect of DXL-A-22 and further to explore the potential mechanisms.Methods The anti-neuropathic pain effect was evaluated by chronic constriction injury(CCI)model.The potential anti-neuropathic pain mechanisms of DXL-A-22 was studied by Western blot and qPCR.The acute toxicity was evaluated by ultimate test.Results DXL-A-22(2,1,0.5 mg·kg-1,i.g.)dose-dependently elevated the mechanical withdrawal threshold(MWT)and the paw withdrawal latency(PWL)in CCI rats(P<0.05,P<0.01),the percentage of pain threshold elevation(PTE%)and the percentage of Maximal Possible Effect(MPE%)was 108%,86%,71% and 77%,56%,43% respectively on day 7 post-operation.DXL-A-22(2 mg·kg-1,i.g.)significantly reduced the expression of p-CaMKⅡα,p-CREB,p-JAK2,p-STAT3 proteins and TNF-α mRNA,c-Fos mRNA in DRG(P<0.05,P<0.01),and the percent inhibition was 37%,48%,35%,58%,39% and 32% respectively.The expression of TNF-α mRNA and c-Fos mRNA in spinal cord was reduced by 47% and 72% respectively in CCI rats(P<0.01).Acute toxicity test showed that DXL-A-22 had no obvious toxicity reaction.Conclusions Spirocyclopiperazinium salt compound DXL-A-22 exerts significant antinociceptive effect on CCI model.The anti-neuropathic pain effect of DXL-A-22 may be related to the inhibition of CaMKⅡα/CREB and JAK2/STAT3 signaling pathways,and the inhibition of the mRNA expression of TNF-α and c-Fos.

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备注/Memo

备注/Memo:
收稿日期:2019-07-20,修回日期:2019-08-16 基金项目:国家自然科学基金资助项目(No 81870876,81470050); 北京市自然科学基金资助项目(No 7122097) 作者简介:梁莹莹(1993-),女,硕士生,研究方向:神经免疫药理学,E-mail:yxyliangying@163.com; 叶 加(1961-),女,博士,教授,硕士生导师,研究方向:神经免疫药理学,通讯作者,E-mail:yejia@bjmu.edu.cn
更新日期/Last Update: 2019-09-15