CAJ | 학술논문

目的：通过建立2型糖尿病（T2DM）胃转流手术（GBP）大鼠模型，探讨对肝脏糖代谢相关因子表达的影响。方法将12只SD大鼠随机分为正常对照组（NCD，n＝4）、高脂组（HFD，n＝4），高脂手术组（HFD-GBP， n＝4）；HFD组大鼠经高脂饲料喂养4周后，通过腹腔注射链脲佐菌素构建T2DM模型，比较两组体质量、血糖、口服葡萄糖耐量实验（OGTT）、胰岛素耐量实验（ITT）的变化。2周后，构建HFD-GBP组胃转流手术模型，连续观察2周，比较手术前后两组体质量、血糖浓度的变化，并分别提取3组大鼠肝组织的总RNA和蛋白，通过RT-PCR、Western印迹法检测法呢醇X受体（FXR）、磷酸烯醇式丙酮酸羧基激酶（PEPCK）、葡萄糖?6?磷酸酶（G6Pase）、葡萄糖转运体2（GLUT2）和成纤维细胞生长因子-21（FGF-21）的表达水平。结果与HFD组相比，HFD-GBP组大鼠体质量下降，血糖改善（P＜0.05），术后FXR和GLUT2 mRNA表达明显上调（P＜0.05），PEPCK、G6Pase和FGF-21 mRNA表达也增加；与NCD组相比，HFD和HFD-GBP两组FXR和PEPCK蛋白表达明显升高（P＜0.05）。结论在T2DM大鼠模型中，GBP能有效改善糖代谢；FXR、PEPCK和GLUT2可能参与GBP术后的血糖调节过程。
목적：통과건립2형당뇨병（T2DM）위전류수술（GBP）대서모형，탐토대간장당대사상관인자표체적영향。방법장12지SD대서수궤분위정상대조조（NCD，n＝4）、고지조（HFD，n＝4），고지수술조（HFD-GBP， n＝4）；HFD조대서경고지사료위양4주후，통과복강주사련뇨좌균소구건T2DM모형，비교량조체질량、혈당、구복포도당내량실험（OGTT）、이도소내량실험（ITT）적변화。2주후，구건HFD-GBP조위전류수술모형，련속관찰2주，비교수술전후량조체질량、혈당농도적변화，병분별제취3조대서간조직적총RNA화단백，통과RT-PCR、Western인적법검측법니순X수체（FXR）、린산희순식병동산최기격매（PEPCK）、포도당?6?린산매（G6Pase）、포도당전운체2（GLUT2）화성섬유세포생장인자-21（FGF-21）적표체수평。결과여HFD조상비，HFD-GBP조대서체질량하강，혈당개선（P＜0.05），술후FXR화GLUT2 mRNA표체명현상조（P＜0.05），PEPCK、G6Pase화FGF-21 mRNA표체야증가；여NCD조상비，HFD화HFD-GBP량조FXR화PEPCK단백표체명현승고（P＜0.05）。결론재T2DM대서모형중，GBP능유효개선당대사；FXR、PEPCK화GLUT2가능삼여GBP술후적혈당조절과정。
Objective To establish a rat model of type 2 diabetes mellitus (T2DM) following by gastric bypass (GBP) surgery, and then determine the effect of GBP on the expression of glycometabolism-related factors in the liver. Methods Twelve 6-week-old SD rats were randomly divided into normal chow diet group (NCD, n=4) and high-fat diet group (HFD, n=8). In 4 weeks after high-fat diet, the rats of the latter group were injected with streptozocin (STZ) intraperitoneally to induce T2DM model. Body mass and blood glucose were measured, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were carried out in the NCD and HFD groups, and the results were compared between them. In 2 weeks later, 4 rats of the HFD group underwent GBP surgery and named as HFD-GBP group. After another 2 weeks, body mass and blood glucose were measured again. The expression of farnesoid X receptor (FXR), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), glucose transporter 2 (GLUT-2) and fibroblast growth factor-21 (FGF-21) at mRNA and protein levels in the liver of the 3 groups of rats were detected by RT-PCR and Western blotting respectively. Results Compared with the HFD group, the HFD-GBP group had significantly decreased body mass and improved blood glucose (P<0.05), obviously up-regulated FXR and GLUT2 at mRNA level (P<0.05), and increased mRNA expression of PEPCK, G6Pase and FGF-21. The protein expression levels of FXR and PEPCK were significantly elevated in HFD and HFD-GBP groups than in the NCD group (P<0.05). Conclusion GBP surgery effectively improves glucose metabolism in T2DM rats. FXR, PEPCK and GLUT2 may participate in the blood glucose regulation after the surgery.