Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Int J Mol Med. 2018 May;41(5):2909-2916. doi: 10.3892/ijmm.2018.3490. Epub 2018 Feb 13.
Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav 1.2 and Cav 2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA. Next, in AR42J cells with either knock-out or overexpression of ghrelin, Cav 1.2 and Cav 2.2 expression was examined using western blot analysis, and intracellular calcium [Ca2+]i was detected with confocal microscopy. In this study, the ghrelin serum level was highest in the ANP group and was higher in the AEP group than the normal group. Expression of Cav 1.2 and Cav 2.2 in the ANP and AEP groups was higher than in the respective control groups. The serum IL-1β and TNF-α levels were significantly higher in the ANP group compared to the other groups. Cav 1.2 and Cav 2.2 expression and [Ca2+]i decreased in ghrelin knockdown AR42J cells but increased in ghrelin overexpressing cells. In conclusion, Cav 1.2 and Cav 2.2 expression increased in ANP. The [Ca2+]i level, which is mediated by Cav 1.2 and Cav 2.2 expression, is directly regulated by ghrelin in pancreatic acinar cells, and serum ghrelin levels may be involved in the severity of acute pancreatitis.
胃饥饿素影响胰腺内分泌和外分泌功能，调节细胞内钙离子 [Ca2+]i 水平，并在急性胰腺炎中具有抗炎作用。本研究探讨了内源性胃饥饿素在急性胰腺炎中 Cav1.2（L 型钙通道）和 Cav2.2（N 型钙通道）表达中的作用。为此，建立了急性水肿性胰腺炎（AEP）和急性坏死性胰腺炎（ANP）大鼠模型。通过免疫组织化学检测大鼠胰腺组织中 Cav1.2 和 Cav2.2 的表达；通过 ELISA 检测血清胃饥饿素、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平。接下来，在敲除或过表达胃饥饿素的 AR42J 细胞中，通过 Western blot 分析检测 Cav1.2 和 Cav2.2 的表达，并用共聚焦显微镜检测细胞内钙离子 [Ca2+]i。在本研究中，ANP 组的血清胃饥饿素水平最高，AEP 组高于正常组。ANP 和 AEP 组的 Cav1.2 和 Cav2.2 表达均高于相应对照组。与其他组相比，ANP 组的血清 IL-1β 和 TNF-α 水平显著升高。胃饥饿素敲低的 AR42J 细胞中 Cav1.2 和 Cav2.2 的表达和 [Ca2+]i 降低，而过表达胃饥饿素的细胞中则增加。综上所述，ANP 中 Cav1.2 和 Cav2.2 的表达增加。由 Cav1.2 和 Cav2.2 表达介导的 [Ca2+]i 水平，在胰腺腺泡细胞中受胃饥饿素的直接调节，血清胃饥饿素水平可能参与急性胰腺炎的严重程度。
