Kim S S, Jang H J, Oh M Y, Lee J H, Kang K S
Department of Anesthesia and Pain Medicine, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea.
Department of Surgery, Ulsan University College of Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea.
Transplant Proc. 2018 Nov;50(9):2847-2853. doi: 10.1016/j.transproceed.2018.03.033. Epub 2018 Mar 16.
The transplantation of isolated pancreatic islets is a promising treatment for diabetes. Curcumin has been used for its pharmacologic effects, such as antidiabetic and anti-inflammatory activities. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative THC treatment can attenuate ischemic damage and apoptosis before islet transplantation.
Islets isolated from Balb/c mice were randomly divided into 2 groups and cultured in medium supplemented with or without THC. In vitro islet viability and function were assessed. After treatment with a cytokine cocktail consisting of tumor necrosis factor-α, interferon-β, and interleukin-1β, islet cell viability, function, and apoptotic status were determined. Proteins related to apoptosis were analyzed using INS-1 cell after streptozocin treatment.
There was no difference in cell viability between the 2 groups. Islets cultured in the medium supplemented with THC showed 1.3-fold higher glucose-induced insulin secretion than the islets cultured in the medium without THC. After treatment with a cytokine cocktail, glucose-induced insulin release, and NO of the islets were significantly improved in THC-treated islets compared with islets not treated with THC. Apoptosis was significantly decreased, and B-cell lymphoma-2 was elevated in the THC-treated group. The streptozocin-treated INS-1 cell produced significantly higher levels of and B-cell lymphoma-2-associated X protein, caspase-3, and caspase-9 than INS-1 treated with THC.
These results suggest that preoperative THC administration enhances islet function before transplantation and attenuates the cytokine-induced damage associated with apoptosis.
孤立胰岛移植是一种很有前景的糖尿病治疗方法。姜黄素因其药理作用,如抗糖尿病和抗炎活性而被使用。四氢姜黄素(THC)是姜黄素的主要代谢产物之一,据报道具有抗氧化和抗炎活性。本研究检验术前THC治疗可减轻胰岛移植前缺血损伤和细胞凋亡这一假设。
从Balb/c小鼠分离的胰岛随机分为2组,在添加或不添加THC的培养基中培养。评估体外胰岛活力和功能。用由肿瘤坏死因子-α、干扰素-β和白细胞介素-1β组成的细胞因子混合物处理后,测定胰岛细胞活力、功能和凋亡状态。用链脲佐菌素处理后的INS-1细胞分析与凋亡相关的蛋白质。
两组细胞活力无差异。在添加THC的培养基中培养的胰岛,其葡萄糖诱导的胰岛素分泌比在不添加THC的培养基中培养的胰岛高1.3倍。用细胞因子混合物处理后,与未用THC处理的胰岛相比,用THC处理的胰岛中葡萄糖诱导的胰岛素释放和一氧化氮水平显著改善。凋亡显著减少,且THC处理组中B细胞淋巴瘤-2升高。与用THC处理的INS-1细胞相比,经链脲佐菌素处理的INS-1细胞产生的B细胞淋巴瘤-2相关X蛋白、半胱天冬酶-3和半胱天冬酶-9水平显著更高。
这些结果表明,术前给予THC可增强移植前胰岛功能,并减轻与细胞凋亡相关的细胞因子诱导的损伤。