白头翁皂苷B4栓剂改善大鼠痛风药效学研究

Pharmacodynamic study of Pulsatilla saponin B4 suppository in treatment of gout in rats

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、52 mg·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。

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(TNFα)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 volumemeasurement 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 B4ointment 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 ofserum uric acid, XOD, and BUN in hyperuricemia rats, and reduce the levels of uric acid, BUN, CRE, and MDA in liver, andincreased 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 byformaldehyde in mice (P < 0.01). Conclusion Pulsatilla saponin B4 suppository had anti-gouty arthritis, acute hyperuricemia, antiinflammatory and analgesic effects.