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链脲佐菌素诱导的小鼠(BALB/c)糖尿病模型并非用于研究1型糖尿病治疗中移植程序的有效模型。

Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes.

作者信息

Wszola Michal, Klak Marta, Kosowska Anna, Tymicki Grzegorz, Berman Andrzej, Adamiok-Ostrowska Anna, Olkowska-Truchanowicz Joanna, Uhrynowska-Tyszkiewicz Izabela, Kaminski Artur

机构信息

Foundation of Research and Science Development, 01-793 Warsaw, Poland.

Chair and Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warsaw, Poland.

出版信息

Biomedicines. 2021 Nov 29;9(12):1790. doi: 10.3390/biomedicines9121790.

Abstract

Type 1 diabetes (T1D) is characterized by the destruction of over 90% of the β-cells. C-peptide is a parameter for evaluating T1D. Streptozotocin (STZ) is a standard method of inducing diabetes in animals. Eight protocols describe the administration of STZ in mice; C-peptide levels are not taken into account. The aim of the study is to determine whether the STZ protocol for the induction of beta-cell mass destruction allows for the development of a stable in vivo mouse model for research into new transplant procedures in the treatment of type 1 diabetes. Forty BALB/c mice were used. The animals were divided into nine groups according to the STZ dose and a control group. The STZ doses were between 140 and 400 mg/kg of body weight. C-peptide was taken before and 2, 7, 9, 12, 14, and 21 days after STZ. Immunohistochemistry was performed. The area of the islet and insulin-/glucagon-expressing tissues was calculated. Mice who received 140, 160, 2 × 100, 200, and 250 mg of STZ did not show changes in mean fasting C-peptide in comparison to the control group and to day 0. All animals with doses of 300 and 400 mg of STZ died during the experiment. The area of the islets did not show any differences between the control and STZ-treated mice in groups below 300 mg. The reduction of insulin-positive areas in STZ mice did not exceed 50%. Streptozotocin is not an appropriate method of inducing a diabetes model for further research on transplantation treatments of type 1 diabetes, having caused the destruction of more than 90% of the β-cell mass in BALB/c mice.

摘要

1型糖尿病(T1D)的特征是超过90%的β细胞被破坏。C肽是评估T1D的一个指标。链脲佐菌素(STZ)是在动物中诱导糖尿病的标准方法。有八种方案描述了在小鼠中施用STZ的方法;但未考虑C肽水平。本研究的目的是确定用于诱导β细胞团块破坏的STZ方案是否能够建立一个稳定的体内小鼠模型,用于研究1型糖尿病治疗中的新移植程序。使用了40只BALB/c小鼠。根据STZ剂量将动物分为九组和一个对照组。STZ剂量在140至400毫克/千克体重之间。在注射STZ之前以及之后的第2、7、9、12、14和21天采集C肽。进行了免疫组织化学分析。计算胰岛以及表达胰岛素/胰高血糖素的组织的面积。接受140、160、2×100、200和250毫克STZ的小鼠与对照组以及第0天相比,平均空腹C肽没有变化。所有接受300和400毫克STZ剂量的动物在实验过程中死亡。在低于300毫克的组中,对照组和接受STZ治疗的小鼠之间的胰岛面积没有显示出任何差异。STZ小鼠中胰岛素阳性区域的减少不超过50%。链脲佐菌素不是诱导糖尿病模型以进一步研究1型糖尿病移植治疗的合适方法,因为它已导致BALB/c小鼠中超过90%的β细胞团块被破坏。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/8698562/83ab327c405b/biomedicines-09-01790-g001.jpg

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