关键词: 髓样细胞白血病因子-1, 胰岛细胞凋亡, 高脂饮食, 肥胖, 2型糖尿病

Abstract: Objective To analyze the expression level of myeloid cell leukemia-1(Mcl-1) and its correlation with cell apoptosis through the establishment of a high-fat diet induced obese rats model, in order to research islet cells injure mechanism. Methods A total of 72 male Sprague-Dawley rats with specific pathogen free (SPF) weaned were randomly assigned to two groups by 1∶2.Finally 24 rats were in normal diet group and 48 rats in high fat diet group.The rats were killed at the end of the 8,16,20,24 weeks of high-fat diet.After that, the obese rats were sieved out and prepared for following experiment.The obese rats were set up as obese group and the normal diet rats were control group.The serum level of free fatty acids was tested by ELISA to analyze the lipid metabolism in obese rats.The microstructure of pancreas was observed by electron microscope.The protein expression of Mcl-1 was examined by immunohistochemical method, and the mRNA level of Mcl-1 was detected by real-time PCR to explore the possible mechanism of obesity β-cell damage in rats.TUNEL method was used to detect islet cell apoptosis situation of the two groups. Results 1) The serum level of free fatty acids of obese rats was significantly higher than that of the control group after high-fat diet for 20 weeks (P<0.01).2) Electron microscope showed that beta-cells in obese group were hyperplastic, and some appeared apoptosis.3) The protein expression level of Mcl-1 was significantly lower in obese group after high-fat diet for 20 weeks (P<0.05).4) Compared with control group, the mRNA level of Mcl-1 was significantly lower in obese group after high-fat diet for 16 weeks (P<0.05).5) The apoptosis rate of the obese group increased significantly than after high-fat diet for 20 weeks (P<0.01).6) The islet cell apoptosis rate of rats was positively correlated with serum FFA(r＝0.536,P<0.01), and negatively correlated with Mcl-1 gene expression(r＝-0.776,P<0.01). Conclusions Islet β-cell morphological abnormalities existed in obese rats, and the expression level of Mcl-1 gene decreases in obese rats.Moreover, rats′ islet cell apoptosis rate was negatively correlated with Mcl-1 gene expression.It is indicated that islet β-cell is damaged in obese rats, and the mechanism might be associated with mitochondrial apoptosis pathway.

Key words: myeloid cell leukemia-1, islet cell apoptosis, high-fat diet, obesity, type 2 diabetes mellitus