Cajal间质细胞介导急性胰腺炎引起的胃肠道动力障碍

Interstitial cells of Cajal mediate acute pancreatitis-caused gastrointestinal dysmotility

目的探讨Oddi括约肌Cajal间质细胞(interstitial cells of Cajal,ICC)在家兔实验性重症急性胰腺炎(severe acute pancreatitis,SAP)中的变化。方法共有16只新西兰雌性白兔随机分为两组(n=8):假手术组和SAP组;逆行注射5%牛磺胆酸钠(1.0 mL/kg)进入胰管建立SAP家兔模型。建模8 h后处死动物。胰腺和Oddi括约肌切除,并进行常规病理检查。免疫组化染色,用于检测Oddi括约肌的c-kit阳性细胞。通过实时聚合酶链反应检测c-kit的mRNA的表达,Western印迹法对c-kit和nNOS蛋白的表达进行了评估。用透射电子显微镜观察ICC的超微结构。结果 SAP组胰腺组织中有出血、坏死和大量的炎性细胞浸润。SAP组Oddi括约肌中c-kit阳性细胞密度(56.11±7.09)明显低于假手术组(88.47±10.49,P<0.01)。SAP组c-kit的蛋白和mRNA水平分别为假手术组的54.7%和47.1%(P<0.01),均明显低于假手术组。SAP组的ICC表现出相同的变化趋势,如线粒体空泡化,不规则的空泡和松动的桥粒样连接。结论c-kit阳性细胞的减少和ICC超微结构的变化导致的c-kit信号通路阻断与SAP引起的肠道运动功能障碍密切相关。

Objective To investigate the changes of the interstitial cells of Cajal （ICC） of sphincter of Oddi in rabbits with severe acute pancreatitis （SAP）. Methods A total of 16 New Zealand white rabbits were randomly divided into 2 groups （ n = 8 ）, a sham operation group （ S group） and a SAP group. Rabbit SAP model was established by retrograde injection of 5% sodium taurocholate （1.0 mL/kg） into the pancreatic duct. Eight hours after the operation, animals were sacrificed. The pancreas and sphincter of Oddi were harvested and undergone routine pathological examination. Immunohistochemical staining was used to detect the c-kit-positive cells in the sphincter of Oddi. The expression levels of c-kit and nNOS were analyzed by real-time polymerase chain reaction and Western blotting. ICC uhrastructure was observed by transmission electron microscopy. Results The pancreatic tissues of the SAP group had hemorrhage, necrosis, and a large number of inflammatory cell infiltration. The c-kit-positive cell density in the sphincter of Oddi in the SAP group was significantly lower than that in the S group. The average c-kit-positive cell density in the S group was 88.47 ± 10.49 and that of the SAP group 56. 11 ± 7.09. Protein and mRNA levels of c-kit in the SAP group were 54.7% and 47.1% of those of the S group. ICC in the SAP group showed mitochondria vacuolization, irregular vacuoles and loosen desmosomes like connection. Conclusion The blockage of c-kit signaling pathway caused by ICC ultrastructural changes and the reduction of c-kit-positive cells is closely related to the intestinal dysmotilitv triggered by SAP.