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目的:研究雄黄和含雄黄复方牛黄解毒片对发热模型大鼠应激蛋白(热休克蛋白HSP70、血红素氧合酶HO-1)、炎症介质(IL-1β、IL-6、TNF-α和NO)和补体(C3、C4)的影响,探讨雄黄在复方中“解毒”作用的机理。方法:SD大鼠随机分为4组(15只/组):正常对照组、发热模型组、雄黄组(90 mg/kg)、牛黄解毒片组(1.404 g/kg);各组再设3个亚组(5只/组),分别于药后1、2、4 h取血。采用ELISA法测定血清中HSP70含量、血清炎症细胞因子IL-1β、IL-6和TNF-α水平;双波长分光光度法测定血清中HO-1活力;比色法测定血清中一氧化氮合酶(NOS)及其同工酶(诱导型一氧化氮合酶iNOS)的活力;免疫比浊法测定血清补体C3、C4水平。结果:雄黄和牛黄解毒片均能显著提高血清HSP70水平;显著增强血清HO-1的活力,且在给药后不同时间的HO-1活力升幅的变化趋势与血清中总砷浓度的变化趋势一致;雄黄和牛黄解毒片均能显著降低血清IL-1β水平,给药后4 h基本回复到正常水平;药后2 h,牛黄解毒片可显著降低血清NOS和iNOS的活力;对血清C3、C4水平均无明显影响。结论:一定剂量的雄黄和牛黄解毒片可诱导、激活发热大鼠体内某些应激蛋白(HSP70、HO-1);并且能抑制病理状态下过度释放的炎症介质(IL-1β),复方的抑制作用大于雄黄。提升机体的应激水平和抑制炎症介质可能是雄黄发挥“解毒”作用的途径。
Objective: To investigate the effects of realgar and realgar containing Niuhuangjiedu tablet on the expression of heat stress protein (heat shock protein HSP70, heme oxygenase HO-1), inflammatory mediators (IL-1β, IL-6, TNF- NO) and complement (C3, C4), to explore the mechanism of realgar in compound prescription. Methods: The SD rats were randomly divided into 4 groups (n = 15): normal control group, fever model group, realgar group (90 mg / kg) and Niu Huang Jiedu Tablet group (1.404 g / kg) A subgroup (5 / group), respectively, 1,2,4 h after taking blood. Serum levels of HSP70, IL-1β, IL-6 and TNF-α in serum were measured by ELISA. The activity of HO-1 in serum was measured by dual-wavelength spectrophotometry. The levels of nitric oxide synthase (NOS) and its isoenzymes (iNOS) were detected by enzyme-linked immunosorbent assay (ELISA). Serum C3 and C4 levels were measured by immunoturbidimetry. Results: Both realgar and Niuhuangjiedu tablet could significantly increase serum HSP70 level and significantly increase the activity of serum HO-1, and the trend of HO-1 activity increase at different time after administration was consistent with that of serum total arsenic concentration ; Realgar and Niuhuang Jiedu Tablet can significantly reduce serum IL-1β levels, 4 h after administration returned to normal levels; 2 h after treatment, Niuhuangjiedu tablets can significantly reduce serum NOS and iNOS activity; serum C3, C4 No significant effect on the level. Conclusion: A certain dose of realgar and Niuhuang Jiedu Tablet can induce and activate certain stress proteins (HSP70, HO-1) in fever rats and inhibit the over-release of inflammatory mediators (IL-1β) Inhibition than realgar. Raising the body’s stress levels and inhibiting the inflammatory mediators may be the way Realgar exerts a “detoxification” effect.