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一种新的垂体功能障碍灵长类动物模型。

A new primate model of hypophyseal dysfunction.

机构信息

Department of Neurosurgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan.

Department of Endocrinology and Diabetes, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

出版信息

Sci Rep. 2021 May 24;11(1):10729. doi: 10.1038/s41598-021-90209-3.

Abstract

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey's general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

摘要

对于垂体再生医学,有必要在猴子中创建垂体模型以进行未来的临床前研究;然而,之前的研究报告表明,在猴子中进行垂体切除术并不总是安全或令人满意的。本研究旨在使用更安全的手术技术在食蟹猴中创建垂体功能障碍模型,并为该模型建立垂体激素替代治疗方案。对一只 7.8 岁、体重 5.45 公斤的健康成年雄性食蟹猴进行经蝶窦内镜下经口经蝶窦垂体切除术,以创建垂体功能障碍模型,用于未来的再生研究。在导航支持下进行经蝶窦内窥镜手术以进行垂体切除术。这些程序有助于确认在不进行额外骨切除的情况下完全切除垂体,并防止脑脊液漏等并发症。通过病理检查和计算机断层扫描确认完全切除。通过内分泌检查包括刺激试验来验证垂体功能减退。术后,对垂体功能减退的猴子的一般情况进行激素替代治疗,从而实现长期生存。微创和安全手术方法的成功以及长期生存表明已在食蟹猴中创建了垂体功能障碍模型;因此,该方案可用于未来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee64/8144576/8beff583ff06/41598_2021_90209_Fig1_HTML.jpg

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