评价利用妊娠期糖尿病模型寻找大鼠子代糖尿病的药物矫正方法的前景

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Pharmacokinetics and Pharmacodynamics Pub Date : 2023-07-20 DOI:10.37489/2587-7836-2023-2-45-53
A. Solomina, A. Rodina, K. Kachalov, A. D. Zakharov, A. Durnev
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引用次数: 0

摘要

妊娠期糖尿病(GDM)导致母体-胎盘-胎儿系统葡萄糖稳态失衡,导致子代产前和产后异常。缺乏普遍认可的gdm模型使寻找预防和纠正后代异常的发病手段变得复杂。采用食物负荷(高热量饮食)联合低剂量糖尿病原链脲佐菌素的模型(HCD-STZ模型)在病因、发展机制和临床发现方面似乎是最接近的。因此,我们的目的是建立和评估GDM的HCD-STZ模型的适用性,以记录后代的异常情况,并确定其药物纠正的可能性。大鼠及其胎儿是研究对象。GDM的建模包括让大鼠保持高热量饮食(NCD)至少10周,然后在妊娠第一天单次注射低剂量STZ。在HCD联合链脲佐菌素25 mg/kg剂量组中,GDM的高血糖特征在不到40%的动物中记录。这一事实不允许对后代的产前和产后发育异常进行可靠的评估。因此,所使用的模型不希望找到GDM对后代影响的药理学纠正方法。
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Evaluating the prospects of using gestational diabetes mellitus model to find means of pharmacological correction of the disorders in rat offspring
Imbalance of glucose homeostasis in the mother-placenta-fetus system in case of gestational diabetes mellitus (GDM) leads to pre- and postnatal abnormalities in offspring. Lack of universally recognized GDM-model complicates the search for pathogenetic means to prevent and correct abnormalities in offspring. A model using food load (high-calorie diet) in combination with low doses of diabetogen streptozotocin (HCD-STZ model) seems to be one of the closest in causes, mechanisms of development and clinical findings. Hence, the aim was to work out and assess the suitability of HCD-STZ model of GDM in order to register abnormalities in the offspring and determine the possibility of their pharmacological correction. Rats and its fetuses were the objects of the study. Modeling of GDM involved keeping rats on a high-calorie diet (NCD) for at least 10 weeks followed by a single injection of low-dose STZ on the first day of gestation. The hyperglycemia characteristic of GDM is recorded in less than 40 % of animals in HCD group combined with streptozotocin at a dose of 25 mg/kg. This fact does not allow a reliable assessment of abnormalities of antenatal and postnatal development of offspring. Thus, the model used is not promising for finding means of pharmacological correction of the effect of GDM on offspring.
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来源期刊
CiteScore
4.90
自引率
4.00%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.
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