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同步进行胰十二指肠切除术和注射链脲佐菌素用于食蟹猴糖尿病建模

Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys.

作者信息

Park H, Park J B, Kim J H, Lee K W, Lee H S, Kim G-S, Shin D-Y, Oh S-H, Jin S-M, Kim S J

机构信息

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Transplant Proc. 2017 Jun;49(5):1142-1149. doi: 10.1016/j.transproceed.2017.03.012.

DOI:10.1016/j.transproceed.2017.03.012
PMID:28583545
Abstract

BACKGROUND

In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM.

METHODS

IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model.

RESULTS

Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys.

CONCLUSIONS

Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals.

摘要

背景

在胰岛移植的实验动物模型中,稳定诱导胰岛素依赖型糖尿病(IDDM)以及从供体胰腺分离胰岛至关重要。在非人灵长类动物中,通过全胰切除术诱导IDDM并获取胰岛会导致外分泌功能不必要的丧失,且可能引发与IDDM相关的疾病。

方法

用链脲佐菌素(STZ)诱导IDDM会伴随STZ的药物毒性,并且需要处死另一只动物来获取胰岛。在本研究中,我们在非人灵长类动物模型中进行了次全胰切除术并联合减少剂量的STZ注射,以诱导IDDM并获取胰岛。

结果

12只食蟹猴在接受次全胰切除术的同时接受了低剂量STZ注射(60mg/kg)。所有猴子术后恢复良好,无并发症。这些动物被诱导出了IDDM。从切除的胰腺中分离出57,691±16,050个胰岛,并移植到其他猴子体内。

结论

次全胰切除术与低剂量STZ注射相结合是一种有效且安全的方法,可创建胰岛素依赖型糖尿病动物模型,同时无需处死额外动物就能提供足够数量的新鲜胰岛细胞用于同种异体移植。

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Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys.同步进行胰十二指肠切除术和注射链脲佐菌素用于食蟹猴糖尿病建模
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引用本文的文献

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Sci Rep. 2021 Apr 21;11(1):8617. doi: 10.1038/s41598-021-88166-y.
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Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model.同种异体胰岛在非人类灵长类动物模型中的整体肝组织学分析。
Sci Rep. 2020 Jan 21;10(1):793. doi: 10.1038/s41598-020-57701-8.