Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation
Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation
复制标题
卡巴胆碱可改善兔颌下腺移植后早期的分泌。
DOI：
10.1111/j.1601-0825.2009.01633.x
复制
发表时间：
2010-05-01
期刊：
影响因子：
3.8
通讯作者：
Yu, G. Y.
中科院分区：
文献类型：
--
作者：
Shi, L.;Cong, X.;Yu, G. Y.
目的：探讨下颌下腺（SMG）移植后毒蕈碱受体信号通路的变化以及卡巴胆碱是否改善移植SMG的分泌。材料与方法：在兔模型中进行自体SMG移植。从术后第1-7天起，将卡巴胆碱（1μM）注入移植的腺体中。通过 RT-PCR、免疫印迹或免疫荧光测量 M1 和 M3 毒蕈碱受体、水通道蛋白-5 (AQP5) 和磷酸化细胞外信号调节激酶 1/2 (p-ERK1/2) 的表达。采用放射免疫法测定肌醇1,4,5-三磷酸(IP3)的含量。结果：移植后SMGs唾液流量减少。此外，M1和M3受体及其下游信号分子IP3、p-ERK1/2和AQP5的表达均降低。移植腺体中显示腺泡细胞萎缩。然而，在卡巴胆碱治疗 7 天后，所有这些改变都被逆转。此外，卡巴胆碱还直接增加培养的新生兔SMG细胞中AQP5的mRNA表达和ERK1/2的磷酸化。结论：乙酰胆碱的缺乏和毒蕈碱受体信号通路的下调与移植的SMGs的早期功能低下有关。卡巴胆碱治疗可能是一种新的治疗策略，可在 SMG 移植后早期改善分泌并预防沃顿管阻塞。
Objectives:To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs.Materials and methods:SMG autotransplantation was performed in a rabbit model. Carbachol (1 mu M) was infused into the transplanted glands from postoperative day 1-7. The expression of the M1 and M3 muscarinic receptors, aquaporin-5 (AQP5), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by RT-PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5-trisphosphate (IP3) was measured by radioimmunoassay.Results:Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP3, p-ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells.Conclusion:A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton's duct in the early phase after SMG transplantation.