摘要
目的 研究白头翁皂苷B4栓剂抗痛风作用.方法 应用混合脂肪酸甘油酯制备白头翁皂苷B4栓剂;使用尿酸钠诱导大鼠急性痛风性关节炎模型,观察白头翁皂苷B4栓剂(9、18、36 mg·kg-1,直肠给药)对大鼠踝关节肿胀度的影响,试剂盒法检测血清炎症因子单核细胞趋化蛋白-1(MCP-1)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,HE染色后观察踝关节组织病理学变化;使用氧嗪酸钾诱导大鼠急性高尿酸血症,给予别嘌醇(阳性药,22 mg·kg-1,ip给药)和白头翁皂苷B4栓剂低、中、高剂量(9、18、36 mg·kg-1),试剂盒法检测大鼠血清中尿酸、黄嘌呤氧化酶(XOD)、尿素氮(BUN)水平,检测肝脏组织中尿酸、BUN、肌酐(CRE)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)水平,HE染色后检测肾脏组织病理学变化;使用角叉菜胶诱导大鼠足肿胀建立炎症动物模型,足容积测量仪观察白头翁皂苷B4栓剂对肿胀率的影响;使用甲醛诱导小鼠致痛模型,观察白头翁皂苷B4栓剂(13、26、52mg·kg-1)对舔足次数的影响.结果 与模型组比较,白头翁皂苷B4栓剂能够显著抑制尿酸钠诱导急性痛风性关节炎大鼠的关节肿胀(P＜0.05、0.01、0.001),降低血清炎症因子MCP-1、TNF-α、IL-6、IL-1β水平(P＜0.05、0.01、0.001);降低氧嗪酸钾诱导的高尿酸血症大鼠血清尿酸、XOD、BUN水平,降低肝脏中尿酸、BUN、CRE和MDA水平,升高肝脏中GSH-Px、CAT水平(P＜0.05、0.01、0.001),改善肾脏组织病理改变;显著抑制角叉菜胶诱导大鼠足肿胀(P＜0.05);显著减少甲醛诱导小鼠致痛模型的舔足次数(P＜0.01).结论 白头翁皂苷B4栓剂具有抗痛风性关节炎、抗急性高尿酸血症及抗炎镇痛作用.
Abstract
Objective To study the anti-gout effect of Pulsatilla saponin B4 suppository.Methods Pulsatilla saponin B4 suppository was prepared using a mixture of fatty acid glycerides;rats were induced with sodium urate to develop acute gouty arthritis,and the effects of the suppository(9,18,36 mg·kg-1,rectal administration)on the degree of ankle edema were observed,and the levels of inflammatory cytokines monocyte chemotactic protein-1(MCP-1),interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)in the serum were detected using a kit,and the pathological changes in the ankle tissue were observed by HE staining;rats were induced with oxalic acid potassium to develop acute hyperuricemia,and allopurinol(a positive control,22 mg·kg-1,ip administration)and the low,medium,and high doses of Pulsatilla saponin B4 suppository(9,18,36 mg·kg-1)were given,and the levels of uric acid,xanthine oxidase(XOD),and blood urea nitrogen(BUN)in the serum were detected using a kit,and the levels of uric acid,BUN,creatinine(CRE),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and catalase(CAT)in the liver tissue were detected,and the pathological changes in the kidney tissue were observed by HE staining;rats were induced with agarose to establish an inflammatory animal model,and the suppository was observed to affect the degree of edema using a foot volume measurement instrument.Mice were induced with formaldehyde to establish a pain model,and the effect of the suppository(13,26,and 52 mg·kg-1)on the number of licking feet was observed.Results Compared with the model group,Pulsatilla saponin B4 ointment could significantly inhibit the joint swelling induced by sodium urate in acute gouty arthritis rats(P＜0.05,0.01,0.001),reduce the levels of inflammatory factors MCP-1,TNF-α,IL-6,and IL-1β in serum(P＜0.05,0.01,0.001),reduce the levels of serum uric acid,XOD,and BUN in hyperuricemia rats,and reduce the levels of uric acid,BUN,CRE,and MDA in liver,and increased the levels of GSH-Px and CAT in liver(P＜0.05,0.01,0.001),improve the pathological changes of renal tissue;significantly inhibit the paw swelling induced by carrageenan(P＜0.05),significantly reduce the licking foot frequency induced by formaldehyde in mice(P＜0.01).Conclusion Pulsatilla saponin B4 suppository had anti-gouty arthritis,acute hyperuricemia,anti-inflammatory and analgesic effects.
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