Effects And Mechanism Of Long-pulse Gastric Electrical Stimulation Restoring Gastric Motility And The Interstitial Cells Of Cajal In Diabetic Rats

Aims To study the changes of gastric emptying and the interstitial cells of cajal in the antrum of diabetic rats.Methods male Sprague Dawley rats (n=12) were randomized into two groups:the diabetes group (DM group, n=6), diabetes model was induced by streptozotocin (STZ, 60mg/kg, i.p.); the normal control group (control group, n=6). Body weight and blood glucose level was measured before modeling and 0,2,4,6 weeks after modeling. At the end of 6th week, gastric emptying was tested with the help of phenol red irrigation method.Western blot and immunofluorescence were applied to assess the expression of c-kit in the antrum. Transmission electron microscopy was adopted to study the ultrastructure of ICC.Results (1) No significant difference was found in body weight between the DM and control groups before modeling; however, at the end of 2,4,6 weeks after modeling, the body weight in the DM group was markedly decreased compared with that in the control group; (2) No significant difference was found in blood glucose level between the DM and control groups before modeling. At the end of 0,2,4,6 weeks after modeling, blood glucose level of the DM group was significantly increased than that in the control group; (3) Gastric emptying was markedly delayed in the DM group compared to the control group ((55.89±3.32)% vs (76.55±2.36)%, (P= 0.0005); (4) The expression of c-kit protein evaluated by western blot in the antrum was significantly decreased compared with the control group; (5) In the immunofluorescence study, the amount of c-kit+ cells was reduced in diabetic group compared with the control group; (6) The ultrastructure of ICC revealed reduced organelles, swelling mitochondria and endoplasmic reticulum in the DM group compared with the control group.Conclusion The gastric emptying in diabetic rats was significantly delayed, the ultrastructure of ICC was damaged and the level of ICC was decreased compared with the control group.AIM:To investigate the effects of IGF-1 signaling pathway and other relative regulatory factor on ICC in diabetic rats.METHODS:The expression of SCF/c-kit, IGF-1 receptors and 5-HT2B, nNOS in gastric antrum was evaluated by western blotting. Distribution of ICCs was shown by immunolabeling of c-kit while smooth muscle cells and IGF-1 receptors was identified by ?-SMA and IGF-1R. The level of IGF-1 in sera was tested by ELISA. The ultrastucture of ICC was shown by transmission electron microscopy.RESULTS:(1) Compared with the control group, the SCF/c-kit and IGF-1 signal pathway was down-regulated and the expression of 5-HT2B and nNOS was significantily reduced in the DM group; (2) Less c-kit+ cells and IGF-1R+ signal in diabetic rats were observed compared with the control group; (3) The average level of IGF-1 in sera in the DM group was severely decreased.CONCLUSION:the SCF/c-kit and IGF-1 signal pathway was down-regulated and the expression of 5-HT2B and nNOS was significantily reduced in the DM group, which was probably associated with the injury and deficiency of ICC.AIM:To investigate the effects of different parameters of GES on ICC and the role of IGF-1 signaling pathway in diabetic rats.METHODS:The expression of c-kit, M-SCF and IGF-1 receptors of gastric antrum was evaluated by western blotting. Distribution of ICCs was shown by immunolabeling of c-kit while smooth muscle cells and IGF-1 receptors was identified by a-SMA and IGF-IR. The level of IGF-1 in sera was tested by ELISA.RESULTS:(1) There was no significant difference of blood glucose in each group before the model; after modeling and after model 2 weeks,4 weeks and 6 weeks, the true and false stimulation group and diabetes group had no obvious difference; (2) There was no significant difference of body weight in each group before the model; after modeling and after model 2 weeks and 4 weeks, body weight of true stimulated rats was not changed compared with diabetic group; after model 6 weeks, body weight of true stimulated rats compared with diabetic group was increased significantly; (3) Gastric emptying in the DM group was delayed, but improved in all GES groups, especially in the GES2 group. (4) The expression of c-kit, M-SCF and IGF-1R was decreased in the DM group, but increased in all GES groups; (5) immunofluorescence showed after GES treatment, more c-kit+cells among a-SMA+ cells in diabetic rats were observed; (6) The average level of IGF-1 in the DM group was severely decreased, but up-regulated in all GES groups, particularly in the GES2 group; (7) Compared with diabetic group, the ultrastructure of ICC in GES groups showed intact cell membrane, nuclear heterochromatin were decreased, swelling of mitochondrial and endoplasmic reticulum were relieved; SMCs in GES groups were arranged in neat rows, no obvious swelling and few larger cytoplasmic vacuole was observed.CONCLUSION:The results suggested that long pulse GES could promote the regeneration of ICC. IGF-1 signaling pathway might be involved in the mechanism of this process, resulting in improved gastric emptying.