方彦玲 许丽萍 连超炜 张浩

【摘要】 目的：探究西格列汀對糖尿病大鼠胰岛β细胞CXC趋化因子10（chemokine ligand-10，CXCL10）及其受体表达的影响。方法：将90只SD大鼠按照随机数字表法分为干预组30只（高脂高糖饲料喂养+西格列汀灌胃）、模型组30只（高脂高糖饲料喂养+生理盐水灌胃）和空白组30只（普通饲料喂养+生理盐水灌胃）。检测两组大鼠给药前后血糖指标变化，苏木精-伊红（hematoxylin-eosin，HE）染色观察胰岛细胞组织学改变，并比较两组大鼠胰岛β细胞CXCL10及其受体mRNA和蛋白水平。结果：治疗前，干预组及模型组FPG、FINS、HOMAIR均明显高于空白组，ISI均明显低于空白组，差异均有统计学意义（P<0.05）;治疗8周后，干预组FPG、FINS、HOMAIR均明显低于模型组，ISI明显高于模型组，差异均有统计学意义（P<0.05）。干预组细胞数少于空白组，但多于模型组，差异均有统计学意义（P<0.05）。干预组CXCL10及CXCL3的mRNA、蛋白表达水平均明显低于模型组，均高于空白组;干预组TLR4的mRNA、蛋白表达水平均显著高于模型组和空白组，差异均有统计学意义（P<0.05）。结论：西格列汀能够明显降低糖尿病大鼠的FPG、FINS水平，并下调糖尿病大鼠胰岛β细胞CXCL10及其受体的表达量。

【关键词】 糖尿病 西格列汀 胰岛β细胞 CXC趋化因子10 CXC趋化因子3

[Abstract] Objective： To investigate the effect of sitagliptin on the expression of CXC chemokine 10 （CXCL10） and its receptor in pancreatic beta cells of diabetic rats. Method： A total of 90 SD rats were divided into 30 intervention group （high-fat high-sugar diet feeding with siglitine gavage）， 30 model group （high-fat high-sugar diet feeding with normal saline gavage） and 30 blank group （general feed feeding with normal saline gavage）.Hematoxylin-eosin （HE） staining was used to observe the histological changes of islet cells， and the mRNA and protein levels of CXCL10 and its receptor were compared between the two groups. Result： Before treatment， FPG， FINS and HOMAIR in the intervention group and model group were significantly higher than those in the blank group， and ISI were significantly lower than that in the blank group， with statistically significant differences （P<0.05）; 8 weeks after treatment， FPG， FINS and HOMAIR in the intervention group were significantly lower than those in the model group， and ISI was significantly higher than that in the model group， with statistically significant differences （P<0.05）. The number of cells in the intervention group was less than that in the blank group， but more than that in the model group， the differences were statistically significant （P<0.05）. The mRNA， protein expression levels of CXCL10 and CXCL3 in the intervention group were significantly lower than those in the model group， and higher than those in the blank group， and the mRNA， protein expression level of TLR4 in the intervention group were significantly higher than those in the model group and the blank group （P<0.05）. Conclusion： Siglitine can significantly reduce the FPG and FINS levels of diabetic rats， and down-regulate the expression of CXCL10 and its receptor in the pancreatic islet of diabetic rats.

[Key words] Diabetes Sitagliptin Islet β cells CXC chemokine ligand-10 CXC chemokine ligand-3

糖尿病是常见的一种代谢疾病，是由环境和遗传因素共同导致的，该病病程长、病情复杂、并发症多[1]。二肽基肽酶4（dipeptidyl peptidase 4 inhibitor，DPP-4）抑制剂是一种新型降糖药，其能够抑制胰岛素降解，增加餐后胰岛素水平[2-3]，其中西格列汀是最常用的一种药物。有研究显示，西格列汀通过抑制DPP-4，上调胰高血糖素样肽-1基因表达，增加胰岛细胞增殖分化，进而降低甘油三酯，改善血糖[4]。CXC趋化因子10（chemokine ligand-10，CXCL10）是趋化因子的一个亚族组成部分，其与受体结合，具有趋化炎性反应的作用，与多种疾病发生均相关[5]。文献[6-7]研究显示，CXCL10参与胰岛β细胞凋亡。目前，有关DPP-4抑制剂西格列汀对糖尿病的治疗效果及糖尿病患者血清中CXCL10的表达意义研究较多[8]，有关DPP-4抑制剂对胰岛β细胞CXCL10及其受体表达的影响研究较少。本研究旨在探讨DPP-4抑制剂西格列汀对CXCL10及其受体表达的影响。……