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目的:观察鸡鸣散(Ji-Ming-San,JMS)对啮齿类动物的毒性及镇痛抗炎作用,探讨其机制及昼夜节律性差异,验证前人关于JMS择时用药的合理性。方法:Bliss法计算JMS半数致死量(LD50)及相同剂量下JMS对小鼠急性死亡率的昼夜差异;热板法、扭体法观察JMS镇痛作用,硝酸还原酶法测定小鼠血清及脑组织一氧化氮(NO)含量及其昼夜差异;耳廓肿胀法和足跖肿胀法观察JMS抗炎作用,紫外分光光度计法测炎症组织前列腺素E2(PGE2)含量及其昼夜差异。结果:JMS对小鼠的急性毒性呈显著的用药时间依赖性,白昼毒性大于夜间;JMS对小鼠模型有良好的镇痛作用,呈昼夜节律性,并与其降低小鼠血清、脑组织NO含量的昼夜差异相吻合;JMS具有良好的抗炎作用,呈昼夜差异性,并与其降低炎性组织中PGE2含量的昼夜差异相吻合。结论:JMS具有良好的镇痛、抗炎作用,并呈昼夜节律性,镇痛作用可能与其降低NO含量有关,抗炎作用可能与其降低PGE2含量有关。
Objective: To observe the toxicity, analgesic and anti-inflammatory effects of Ji-Ming-San (JMS) on rodents, to explore the mechanism and circadian rhythm difference, and to verify the rationality of predecessors’ JMS chronotherapy. METHODS: Bliss method was used to calculate the LD50 of JMS and the difference of day and night in acute mortality of mice treated with JMS at the same dose. The analgesic effect of JMS was observed by hot plate method and writhing method. The serum and brain of mice were measured by nitrate reductase method. Tissue nitric oxide (NO) content and its diurnal variation; ear swelling method and foot edema swelling method to observe the anti-inflammatory effect of JMS, UV spectrophotometer method to measure prostaglandin E2 (PGE2) content of inflammatory tissue and its diurnal differences. RESULTS: The acute toxicity of JMS to mice was time-dependent, and the toxicity of white fleas was greater than that of nocturnal. JMS had a good analgesic effect in mice models and showed circadian rhythm, and it reduced the serum NO and NO content in mice’s serum and brain. The day-night difference was consistent; JMS had a good anti-inflammatory effect, showing diurnal variation, which was consistent with the diurnal variation of PGE2 content in inflammatory tissues. Conclusion: JMS has good analgesic and anti-inflammatory effects, and is circadian rhythm. The analgesic effect may be related to the decrease of NO content, and the anti-inflammatory effect may be related to the decrease of PGE2 content.