机构地区:[1]广州中医药大学临床药理研究所,广东广州510405
出 处:《中药材》2009年第1期73-78,共6页Journal of Chinese Medicinal Materials
基 金:国家自然科学基金资助项目(30672637)
摘 要: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 explore the pharmacological mechanism of Realgar by the way of studying the effects of Realgar and the prescription containing Realgar named Niuhuang Jiedu Tablet on stress response proteins ( heat shock protein 70, HSP70 and heme oxygenase-1, HO-1 ),inflammatory cytokines (IL-1β,IL-6 and TNF-α), activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS), and complements C3, C4 under pathologic status (fever model). Methods: SD ruts were randomly divided into four groups,15 rats in each: untreated normal group, fever model group, Realgar (90 mg/kg) group and Niuhuang Jiedu Tablet (NJT, 1. 404 g/kg) group. Each group was divided into three subgroups (5 ruts/subgroup). Blood samples of the rats in subgroups were collected at 1 h, 2 h and 4 h after administration, respectively. ELISA method was used to determine HSP70, IL-1β, IL-6, and TNF-α levels in serum. Dual wavelength spectrophotometry was used to determine activity of HO-1 in serum. Spectrophotometry was used to test activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS) in serum. Immunonephelometery method was used to test complements C3, CA in serum. Results: Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group. The increase ranges of HO-1 activities at different time post administration changed with the arsenic concentration in rut serum. Realgar and NJT significantly decreased the level of IL-1β in rat serum as compared with fever model group, and the level of IL-1β recovered normaly at 4 h after administration. NJT significantly inhibited activities of NOS and iNOS in rat serum as compared with the fever model group at 2 h after administration. Conclusion: Realgar as contained in certain prescriptions, at certain specific lev
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