摘要
目的:研究氧化槐定碱(oxysophoridine,OSR)缓解神经病理性疼痛(neuropathic pain,NP)的机制。方法:通过测定机械痛敏,观察OSR的镇痛效果;通过将OSR与γ-氨基丁酸(gamma aminobutyric acid,GABA)合成、代谢相关的激动剂和拮抗剂联用,研究OSR镇痛作用与GABA能神经系统相关机制;采用免疫荧光染色法检测大脑和脊髓内c-Fos免疫阳性细胞表达及c-Fos和谷氨酸脱羧酶(glutamic acid decarboxylase 67,GAD67)、GABA转运体1(γ-aminobutyric acid transporter 1,GAT-1)免疫阳性细胞共表达情况。结果:与Sham组比较,坐骨神经分支选择性损伤(spared nerve injury,SNI)组小鼠机械痛敏升高,c-Fos免疫阳性细胞表达增多,c-Fos和GAD67、GAT-1免疫阳性细胞共表达分别减少和增多。与SNI组比较,OSR 500、1000 mg/kg组机械痛敏降低,OSR 250 mg/kg与拮抗剂联用组痛敏降低,OSR 500 mg/kg与激动剂联用组痛敏升高,OSR 500 mg/kg组小鼠大脑和脊髓的c-Fos和GAD67免疫阳性细胞共表达增多,c-Fos和GAT-1共表达减少。结论:OSR对SNI所致NP小鼠有良好的镇痛作用,可能与通过上调大脑和脊髓中GABA能神经元,增加中枢GABA含量相关。
AIM:To study the mechanism of oxysophoridine(OSR)in relieving neuropathic pain(NP).METHODS:The analgesic effect of OSR was observed by measuring mechanical pain sensitivity.By combining OSR with agonists and antagonists related to synthesis and metabolism of gamma aminobutyric acid(GABA),the mechanism related to analgesic effects of OSR and GABA nervous system is studied.The expression of c-Fos immunopositive cells and the expression of c-Fos and Glutamic acid decarboxylase(Glutamic acid decarboxylase 67)in brain and spinal cord were detected by immunofluorescence staining.Co-expression of GAD67,GABA transporter 1(gamma-Aminobutyric acid Transporter 1,GAT-1)immunopositive cells.RESULTS:Compared with Sham group,spared nerve injury(SNI)group showed increased mechanical pain sensitivity,increased expression of c-Fos immunopositive cells, decreased and increased co-expression of c-Fos and GAD67 and GAT-1 immunopositive cells, respectively.Compared with SNI group, mechanicalalgesia in OSR 500 and 1 000 mg/kg groups was decreased,algesia in OSR 250 mg/kg combined withantagonist group was decreased, and algesia inOSR 500 mg/kg combined with agonist group wasincreased. The co-expression of c-Fos and GAD67immunopositive cells in the brain and spinal cordof OSR 500 mg/kg group increased, while the co-expressionof c-Fos and GAT-1 decreased. CONCLUSION:OSR has a good analgesic effect on NP miceinduced by SNI. The mechanism is that OSR increasesthe content of central GABA by up-regulatingGABAergic neurons in brain and spinal cord.
作者
成帆
石磊
张秀娟
呼延丽
高进贤
CHENG Fan;SHI Lei;ZHANG Xiujuan;HU Yanli;GAO Jinxian(Department of Pharmacy,Gansu Provincial Hospital,Lanzhou 730000,Gansu,China;School of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu,China;Department of Medical Quality Control,Gansu Provincial Hospital,Lanzhou 730000,Gansu,China)
出处
《中国临床药理学与治疗学》
北大核心
2025年第9期1165-1173,共9页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
甘肃省科学技术厅自然科学基金(20JR10RA383,23JRRA1773,24JRRA1056,25JRRA875)
甘肃省人民医院院内科研基金(20GSSY4-26)。
