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目的:考察两种内毒素致热模型用于中药质量控制生物学评价的可能性及应用条件。方法:用细菌内毒素(lipopo-lysaccharide,LPS)皮下注射建立大鼠急性高热模型,以及用LPS皮下缓释建立大鼠持续发热模型,测定急性高热模型体温、血浆肿瘤坏死因子α(TNF-α)和白介素1β(IL-1β)浓度,以研究将其作为体内“微观指标”的可能性;采用大黄及补中益气汤作用于上述两种模型,检测药物对模型体温的干预,以考察模型对不同作用机理药物的适用性及对药量变化的敏感性。结果:TNF-α和IL-1β与动物体温有明显相关性,但其变化迅速,难以用作检测指标。大黄一次灌服可有效抑制LPS所致大鼠急性高热,呈明显的剂量依赖;补中益气汤连续给予4d可显著降低持续发热模型动物的体温。结论:LPS皮下注射所致大鼠急性发热和皮下缓释所致大鼠持续发热两个模型机理比较清楚、方法较稳定,以体温作为检测指标简单可靠,有望用于相应解热中药质量的生物学评价。
OBJECTIVE: To investigate the feasibility and application conditions of two endotoxin thermotolerance models for biological evaluation of quality control of traditional Chinese medicine. Methods: A rat model of acute hyperthermia was subcutaneously injected with lipopolysaccharide (LPS), and the model of sustained fever in rats was established by subcutaneous slow release of LPS. The body temperature, plasma levels of tumor necrosis factor α (TNF-α ) And interleukin-1β (IL-1β) in order to study the possibility of using it as a “microindicator” in vivo. The effects of rhubarb and Bu Zhong Yi Qi Tang on the above two models were tested for the intervention of drugs on body temperature. To investigate the model of different mechanisms of action of drug applicability and sensitivity to changes in the dose. Results: TNF-α and IL-1β had significant correlation with body temperature of animals, but their changes were rapid and hard to be used as detection indexes. Rhubarb once perfused can effectively inhibit LPS-induced acute hyperthermia in a dose-dependent manner; Buzhongyiqi continuous 4d can significantly reduce the body temperature of animals with persistent fever. CONCLUSION: The mechanism of acute fever and subcutaneous sustained release in rats induced by subcutaneous injection of LPS is relatively clear. The two methods are relatively stable. The body temperature is simple and reliable, which is expected to be used for the corresponding quality of the animals Evaluation.