摘要
目的研究青花椒碱对慢性炎性疼痛小鼠的作用和机制。方法将C57BL/6小鼠随机分为5组:正常对照组、模型组、吲哚美辛组(5 mg/kg)和青花椒碱低(10 mg/kg)、高(40 mg/kg)剂量组,每组6只。除正常对照组外,其余各组小鼠均采用左后足下注射完全弗氏佐剂的方法,诱导慢性炎性疼痛小鼠模型。诱导3 d后,按对应分组开始口服给药,连续给药3 d,正常对照组和模型组给予等体积生理盐水。给药结束后,采用机械性缩足阈值(PWT)和热缩足潜伏期(PWL)评价小鼠疼痛程度;使用试剂盒检测血清致痛因子和炎症因子水平;采用代谢组学方法表征血清代谢物水平,并进行差异代谢物和代谢通路分析;通过Western Blot检测左足组织代谢通路相关蛋白表达。结果与正常对照组比较,模型组小鼠PWT和PWL明显降低(P<0.05),血清致痛因子和炎性因子水平明显升高(P<0.05);与模型组比较,青花椒碱组小鼠PWT、PWL、血清致痛因子和炎性因子水平均得到明显逆转(P<0.05)。血清代谢组学发现花生四烯酸代谢可能为青花椒碱主要调控途径。与正常对照组比较,模型组小鼠左足组织环氧合酶-2(COX-2)和脂氧合酶-5(LOX-5)表达明显升高(P<0.05),细胞色素P4504A(CYP4A)表达明显降低(P<0.05);与模型组比较,青花椒碱组小鼠左足COX-2、LOX-5和CYP4A表达均得到明显逆转(P<0.05)。结论青花椒碱对慢性炎性疼痛小鼠具有明显的镇痛作用,其机制可能与其抑制花生四烯酸代谢有关。
Objective To investigate the effects and mechanisms of schinifoline on chronic inflammatory pain in mice.Methods C57BL/6 mice were randomly divided into five groups:normal control group,model group,indomethacin group(5 mg/kg),and low-dose(10 mg/kg)and high-dose(40 mg/kg)groups of schinifoline,with 6 mice in each group.Except for the normal control group,all other groups of mice were induced with chronic inflammatory pain mouse models by injecting complete Freund's adjuvant into the left posterior foot.After 3 days of induction,oral administration was started according to the corresponding groups for 3 consecutive days.The normal control group and model group were given equal volumes of physiological saline.After drug administration,paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were measured to evaluate pain levels;levels of serum algesic factors and inflammatory cytokines were detected using commercial kits;the serum metabolite profiles were characterized via metabolomics,followed by differential metabolite and pathway analysis;Western Blot was used to detect protein expression of pathway-related molecules in the left paw tissue.Results Compared with the normal control group,the model group exhibited significantly decreased PWT and PWL(P<0.05),with markedly elevated levels of serum algesic factors and inflammatory cytokines(P<0.05).Compared with the model group,schinifoline-treated groups showed significant reversal in PWT,PWL,and the levels of serum algesic factors and inflammatory cytokines(P<0.05).The serum metabolomics revealed that arachidonic acid metabolism might be the main regulatory pathway of schinifoline.Compared with the normal control group,the model group showed significantly increased expression of cyclooxygenase-2(COX-2)and lipoxygenase-5(LOX-5)and decreased expression of cytochrome P4504A(CYP4A)in left paw tissue(P<0.05).Compared with the model group,schinifoline groups exhibited significant reversal in the expression of COX-2,LOX-5,and CYP4A(P<0.05).Conclusion Schinifoline has a significant analgesic effect in mice with chronic inflammatory pain,and its mechanism may be related to its inhibition of arachidonic acid metabolism.
作者
张雪琴
严宝飞
郑康
张鹏鹏
ZHANG Xueqin;YAN Baofei;ZHENG Kang;ZHANG Pengpeng(Department of Anesthesiology,Pukou Traditional Chinese Medicine Hospital Affiliated to China Pharmaceutical University,Nanjing 211800,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046,China)
出处
《药学前沿》
2026年第1期52-60,共9页
China Pharmacist
基金
南京市卫生科技发展专项资金项目(YKK23235)
江苏医药职业学院校地协同创新研究项目(20239704)。
关键词
青花椒碱
完全弗氏佐剂
慢性炎性疼痛
代谢组学
花生四烯酸
镇痛
代谢通路
Schinifoline
Complete Freund’s adjuvant
Chronic inflammatory pain
Metabolomics
Arachidonic acid
Analgesia
Metabolic pathway
