糖尿病大鼠胃窦SCF-Kit信号改变及其对Cajal间质细胞的影响

Change of c-Kit/SCF signaling system and its effect on interstitial cells in gastric antrum of diabetic rats

目的研究糖尿病胃轻瘫大鼠胃Cajal间质细胞(interstitialcellsofCajal,ICC)的形态学改变,测定干细胞因子(stemcellfactor,SCF)及Kit含量变化,探讨糖尿病大鼠胃窦SCF-Kit信号在Cajal间质细胞受损中作用。方法用链尿佐菌素建立大鼠糖尿病模型,3个月后采用美蓝方法测定胃排空速率,对胃窦组织进行透射电镜观察Cajal间质细胞超微结构变化,采用RT-PCR方法测定胃窦平滑肌组织SCFmRNA的表达,Westernblot法检测胃窦平滑肌组织c-kit蛋白变化结果与正常大鼠相比,糖尿病大鼠胃排空明显延迟,胃Cajal间质细胞与其他细胞间的缝隙连接显著减少、结构破坏、连接松散;细胞器变性、减少;胞质广泛溶解;核周间隙增宽。糖尿病大鼠胃窦平滑肌组织SCFmRNA以及c-kit蛋白表达均明显低于正常大鼠。结论SCF-Kit系统受损与糖尿病大鼠胃窦Cajal间质细胞变性、数量减少以及网络结构破坏有关最终导致胃运动障碍。

Objective To investigate the changes of c-Kit/SCF signaling system in gastric antrum of diabetic rats and clarify their effects on interstitial cells of Cajal. Methods Wistar rats were randomly divided into diabetic group and control group. The rats in diabetic group were intraperitoneally injected of streptozotocin, while normal saline for control group. Gastric emptying rate was measured, the ultrastructure of antral tissue was observed through transmission electron microscope, the expressions of SCF mRNA and c-kit protein in muscular layer were measured after diabetic rat model establishment for 3 months. Results In the diabetic rats, gastric emptying time was significantly longer than that of normal rats. The number of the gap junction of interstitial cells of Cajal in gastric antrum of diabetic rats decreased significantly, the ultrastructure and the organelle were damaged, and vacuoles were formed. The expression of SCF mRNA and c-kit protein in muscular layer in gastric antrum of diabetic rats was significantly decreased as compared with that in normal rats. Conclusion c- Kit/SCF signaling system is crucial to the development, phenotype maintenance and function of interstitial cells of Cajal. The degeneration and decrease of interstitial cells of Cajal and loosening of network in gastric antrum of diabetic rats occurred because of impairment of c-kit/SCF signaling system.