3种四逆汤抗脓毒症的药效学差异及急性毒性研究

Study on the Different Effects on a Sepsis Model and Acute Toxicity of Three Kinds of Sini Decoction

目的:比较《中国药典》收录四逆汤、《伤寒论》记载四逆汤及云南省首届国医名师吴荣祖教授经验方四逆汤对小鼠脓毒症模型的药效学差异及急性毒性。方法:采用小鼠盲肠结扎穿孔法复制脓毒症模型,给予3种四逆汤。以动物死亡率、血清炎症因子TNF-α、IL-1β、IL-6含量为指标,比较3种四逆汤药效学差异;小鼠经口给予3种四逆汤水煎液,以小鼠最大给药量测定方法比较3种四逆汤的急性毒性差异。结果:药效学研究结果显示,3种四逆汤均对小鼠盲肠结扎穿孔法致脓毒症模型具有生存保护作用,可降低小鼠死亡率,3种四逆汤均可不同程度减少模型动物血清中炎症因子含量,减轻炎症反应,吴荣祖教授经验方四逆汤减少血清中TNF-α含量较为明显;病理组织学检查显示,3方均可减轻模型动物肺及肝脏损伤;急性毒性实验结果显示,小鼠单次给药的最大给药量:吴荣祖先生经验方四逆汤(288 g生药/kg)>《中国药典》收录四逆汤(256 g生药/kg)>《伤寒论》记载四逆汤(125 g生药/kg)。结论:3种四逆汤均具有一定抗小鼠脓毒症作用,在减少血清中炎症因子TNF-α含量方面吴荣祖先生经验方四逆汤作用较为明显,小鼠经口单次给药的急性毒性以吴荣祖先生经验方四逆汤毒性较低。

Objective To compare the acute toxic effect and pharmacodynamicsof a sepsis model on Sini decoctionfromChinese Pharmacopoeia,Treatise on Febrile Diseasesand Empirical Formula of Wu Rongzu,a famous Chinese medicine practitioner in Yunnan Province.Methods Comparison of the acute toxicity of three kinds of Sini decoction on mice were studied in accordance with classical acute toxicity test methods.The sepsis model was established using cecal ligation and puncture.Three kinds of Sini decoction were administered to mice.The mortality of mice was hematoxylin and eosin stain to compare pharmacodynamics differences with three kings of Sini observed and the serum,lung and livertissue sample were collected.The serum tumor necrosis factor–α(TNF-α),interleukin–1β(IL-1β)and interleukin-6(IL-6)were assayed by ELISA and the pathological changes of the lung and liver tissue were analyzed by decoction.Results The maximum dose were assessed after single dosing,followed by Sini decoction from Empirical Formula of Wu Rongzu(288 g/kg),Chinese Pharmacopoeia(256 g/kg)and the least is the Sini decoction from Treatise on Febrile Diseases(125 g/kg).The results of pharmacodynamic studies showed that three kinds of Sini decoction have protective effect on sepsis model.They could significantly reduce mortality and the content of inflammatory factor to varying degrees.It is obvious that the Sini decoction from Empirical Formula of Wu Rongzu could significantly reduce the content of TNF-α.Histopathological examination showed that three kinds of Sini decoction could alleviate lung and liver damage and reduce inflammation in model animals.Conclusion The Sini decoction from Empirical Formula of Wu Rongzuis less toxic in acute toxicity and significantly reduce the content of TNF-αin the anti-sepsis pharmacodynamics among three kinds of Sini Decoction.