脂肪肝诱导过程中实验动物体内 1,3,7-三甲基黄嘌呤的清除情况

O. Popova, V. S. Ponamarev, A. Kostrova, L. Agafonova
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摘要

肝脏病变在改变包括 1,3,7-三甲基黄嘌呤在内的多种药理活性物质的代谢和清除率方面发挥着重要作用,其原因在于肝脏病变对调节外源性生物活性物质生物转化的酶系统产生了影响。目前,人们正在积极研究各种肝胆疾病,尤其是慢性肝胆疾病中咖啡因清除率的变化,因为根据一些研究人员的研究,正是这类病症的特点是三甲基黄嘌呤药代动力学特征发生了最可预测和最稳定的变化。 这项研究的目的是确定在诱导实验动物(大鼠)患脂肪肝时血清中咖啡因水平的变化。研究在圣彼得堡国立医科大学联邦国家高等教育预算教育机构药理学和毒理学系的活体动物馆中进行。 为了进一步比较 "咖啡因曲线",本研究选择了之前一系列实验中的实验动物。根据药理学和毒理学系开发的方法,使用硫酸锶模拟脂肪肝。 诱导完成后,根据临床和生化指标确认脂肪性肝炎。 根据所进行的研究,我们可以得出结论,这两者之间存在一定的相关性。 例如,在脂肪性肝炎中,咖啡因的消除速度并没有明显减慢,而是出现了一个特征性的长高原(用药后长达 8 小时),随后浓度平稳下降。实验数据可用于创建一个数据库,以评估药代动力学与动物生理状态之间的关系。还需要在其他动物物种上进行类似的实验,这将为兽医专家提供全面的信息,有助于评估病理情况。
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Elimination of 1,3,7-trimethylxanthine in laboratory animals during the induction of fatty hepatosis
Liver pathologies play a significant role in changing the metabolism and clearance of a  number  of  pharmacologically  active  substances,  including  1,3,7-trimethylxanthine, which is explained by their influence on enzyme systems that regulate the biotransformation of exogenous biologically active substances. Currently, changes in caffeine clearance  are  being  actively  studied  in  various hepatobiliary disorders, especially those that are chronic, since it is precisely such pathologies, according to a number of researchers, that are characterized by the most predictable  and  stable  change  in  the  trimethylxanthine  pharmacokinetic  profile.  The  purpose of  the  study  was  to  determine  changes  in serum  caffeine  levels  when  inducing  fatty liver  disease  in  laboratory  animals  (rats). The studies were carried out in the vivarium of  the  Department  of  Pharmacology  and Toxicology  of  the  Federal  State  Budgetary Educational Institution of Higher Education of St. Petersburg State University of Medicine.  Laboratory  animals  from  a  previous series of experiments were selected for the study  in  order  to  further  compare  the “caffeine curves.” Fatty hepatosis was modeled using strontium sulfate according to the methodology  developed  at  the  Department of  Pharmacology  and  Toxicology.  Upon completion of induction, fatty hepatosis was confirmed based on clinical and biochemical signs.  Based  on  the  studies  conducted,  we can conclude that there are certain correlations.  For  example,  in  fatty  hepatosis,  the elimination  of  caffeine  is  not  significantly slowed down with a characteristic long plateau (up to 8 hours after administration), turning into a smooth decrease in concentration. Experimental  data  can  be  used  to  create  a database to assess the relationship between pharmacokinetics and the physiological state of animals. Similar experiments need to be carried out on other animal species, which will create a holistic picture and help in assessing  pathologies  for  veterinary  specialists.
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