Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function.
Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function.
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DOI：
10.1038/s41598-023-35820-2
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发表时间：
2023-06-05
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性胰腺炎是一种使人衰弱的疾病，影响着全世界数百万人。这些患者遭受阵阵剧烈疼痛，止痛药物只能勉强缓解疼痛，并且可能需要进行大手术，发病率和死亡率很高。此前，我们证明了“化学胰腺切除术”，即胰腺导管内输注稀乙酸溶液，可以消融外分泌胰腺，同时保留内分泌胰腺。值得注意的是，化学胰腺切除术解决了慢性炎症，减轻了雨蛙胰腺炎模型中的异常性疼痛，并改善了葡萄糖稳态。在此，我们广泛测试了化学胰腺切除术在 NHP 中的可行性，并验证了我们之前发表的试点研究。我们对腹部和骨盆进行了连续计算机断层扫描 (CT) 扫描，分析了背根神经节，测量了血清酶，并进行了组织学和超微结构评估以及胰腺内分泌功能测定。根据连续 CT 扫描，化学胰腺切除术导致胰腺体积损失。免疫组织化学和透射电子显微镜证明外分泌胰腺消融与内分泌胰岛保存。重要的是，化学胰腺切除术并没有增加收获的背根神经节中的促伤害性标记物。此外，化学胰腺切除术将体内和体外的胰岛素分泌提高到超正常水平。因此，这项研究可能为将该手术应用于慢性胰腺炎或其他需要胰腺切除术的患者提供基础。
Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that “chemical pancreatectomy,” a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.
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DOI：
10.1016/j.pan.2017.11.012
发表时间：
2018-01
期刊：
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
影响因子：
--
作者：
Machicado JD;Chari ST;Timmons L;Tang G;Yadav D
通讯作者：
Yadav D
DOI：
10.1016/j.cgh.2020.10.036
发表时间：
2022-01
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Faghih M;Phillips AE;Kuhlmann L;Afghani E;Drewes AM;Yadav D;Singh VK;Olesen SS;Pancreatic Quantitative Sensory Testing (P-QST) Consortium
通讯作者：
Pancreatic Quantitative Sensory Testing (P-QST) Consortium
影响因子：
3.9
作者：
MCGEACHIN, RL;GLEASON, JR;ADAMS, MR
通讯作者：
ADAMS, MR
影响因子：
3.1
作者：
Ramsey ML;Conwell DL;Hart PA
通讯作者：
Hart PA
DOI：
10.2174/1871530320666200423095700
发表时间：
2020
期刊：
Endocrine, metabolic & immune disorders drug targets
影响因子：
--
作者：
Kandikattu HK;Venkateshaiah SU;Mishra A
通讯作者：
Mishra A