山东医药
山東醫藥
산동의약
SHANDONG MEDICAL JOURNAL
2015年
20期
14-17
,共4页
糖尿病%西格列汀%胰岛细胞%细胞凋亡%自噬相关因子%含半胱氨酸的天冬氨酸蛋白水解酶
糖尿病%西格列汀%胰島細胞%細胞凋亡%自噬相關因子%含半胱氨痠的天鼕氨痠蛋白水解酶
당뇨병%서격렬정%이도세포%세포조망%자서상관인자%함반광안산적천동안산단백수해매
diabetes mellitus%sitagliptin%apoptosis%antophagy related fuctors%caspases
目的：观察西格列汀对2型糖尿病小鼠胰岛β细胞自噬相关因子Atg3、Atg12与Beclin1表达的影响，探讨其治疗机制。方法将30只9周龄雄性db／db小鼠随机平均分为2组，DT组灌胃给予西格列汀（80 mg／kg）， DC组给予等量饮用水，每日给药1次，治疗5周。测定血糖、血清胰岛素与组织胰岛素水平；免疫荧光技术观察胰岛形态结构；实时荧光定量PCR法分析胰岛β细胞Atg3、Atg12与Beclin1 mRNA的表达；免疫组织化学方法测定胰岛β细胞Beclin1蛋白表达；并盒分析胰岛β细胞Caspase3活性改变。结果西格列汀治疗5周后，与DC组比较， DT组小鼠血糖降低（P＜0．01），血清胰岛素及组织胰岛素水平增加（P均＜0．01）。 DC组小鼠胰岛α细胞散布于胰岛中，所占比例大；DT组小鼠胰岛β细胞居于胰岛中央部，所占比例大。与DC组相比，DT组小鼠胰岛β细胞Caspase 3活性及Atg12、Atg3、Beclin1 mRNA相对表达降低（P均＜0．01），Beclin1蛋白表达减少（P＜0．01）。结论西格列汀通过下调2型糖尿病小鼠胰岛β细胞自噬相关因子Atg12、Atg3与Beclin1的表达，抑制胰岛β细胞凋亡，改善胰岛的结构与β细胞功能。
目的：觀察西格列汀對2型糖尿病小鼠胰島β細胞自噬相關因子Atg3、Atg12與Beclin1錶達的影響，探討其治療機製。方法將30隻9週齡雄性db／db小鼠隨機平均分為2組，DT組灌胃給予西格列汀（80 mg／kg）， DC組給予等量飲用水，每日給藥1次，治療5週。測定血糖、血清胰島素與組織胰島素水平；免疫熒光技術觀察胰島形態結構；實時熒光定量PCR法分析胰島β細胞Atg3、Atg12與Beclin1 mRNA的錶達；免疫組織化學方法測定胰島β細胞Beclin1蛋白錶達；併盒分析胰島β細胞Caspase3活性改變。結果西格列汀治療5週後，與DC組比較， DT組小鼠血糖降低（P＜0．01），血清胰島素及組織胰島素水平增加（P均＜0．01）。 DC組小鼠胰島α細胞散佈于胰島中，所佔比例大；DT組小鼠胰島β細胞居于胰島中央部，所佔比例大。與DC組相比，DT組小鼠胰島β細胞Caspase 3活性及Atg12、Atg3、Beclin1 mRNA相對錶達降低（P均＜0．01），Beclin1蛋白錶達減少（P＜0．01）。結論西格列汀通過下調2型糖尿病小鼠胰島β細胞自噬相關因子Atg12、Atg3與Beclin1的錶達，抑製胰島β細胞凋亡，改善胰島的結構與β細胞功能。
목적：관찰서격렬정대2형당뇨병소서이도β세포자서상관인자Atg3、Atg12여Beclin1표체적영향，탐토기치료궤제。방법장30지9주령웅성db／db소서수궤평균분위2조，DT조관위급여서격렬정（80 mg／kg）， DC조급여등량음용수，매일급약1차，치료5주。측정혈당、혈청이도소여조직이도소수평；면역형광기술관찰이도형태결구；실시형광정량PCR법분석이도β세포Atg3、Atg12여Beclin1 mRNA적표체；면역조직화학방법측정이도β세포Beclin1단백표체；병합분석이도β세포Caspase3활성개변。결과서격렬정치료5주후，여DC조비교， DT조소서혈당강저（P＜0．01），혈청이도소급조직이도소수평증가（P균＜0．01）。 DC조소서이도α세포산포우이도중，소점비례대；DT조소서이도β세포거우이도중앙부，소점비례대。여DC조상비，DT조소서이도β세포Caspase 3활성급Atg12、Atg3、Beclin1 mRNA상대표체강저（P균＜0．01），Beclin1단백표체감소（P＜0．01）。결론서격렬정통과하조2형당뇨병소서이도β세포자서상관인자Atg12、Atg3여Beclin1적표체，억제이도β세포조망，개선이도적결구여β세포공능。
Objective To investigate the effect of sitagliptin treatment on the expression of autophagy related genes Atg3, Atg12 and Beclin1 in the islet βcells of type 2 diabetic mice.Methods Thirty nine-month-old male db/db mice were randomly divided into two groups , mice in the sitagliptin treatment group ( DT group ) were intragastrically adminis-tered with sitagliptin (80 mg/kg), and mice in the diabetic control group (DC group) were administered with the same a-mount of water .All drug and water was administered once a day for five weeks .Blood glucose , plasma insulin and pancre-atic insulin content were examined .The morphology of islets was analyzed by immunofluorescence .The mRNA expression of Atg3, Atg12 and Beclin1 in the isletβcells was determined by real-time fluorescent quantitative PCR .The expression of Beclin1 protein was examined by immunohistochemistry .The caspase3 activity in the islet βcells was analyzed by commer-cial kit.Results After five-week treatment with sitagliptin , the blood glucose levels in the DT group were lower than those of the DC group (P<0.01), and plasma insulin and pancreatic insulin content were increased significantly in the DT group as compared with those of the DC group (all P<0.01).Theαcells in the DC group distributed to the whole islets with higher proportion , and βcells in the DT group mainly located in the center of islet with high proportion .The mRNA expression of Atg3, Atg12 and Beclin1 in the DT group was significantly decreased as compared with that of the DC group (all P<0.01), and the Beclin1 protein expression was decreased in the DT group as compared with that of the DC group (P<0.01).Conclusion Sitagliptin inhibits the islet βcell apoptosis and improves islet structure and βcell function by down-regulating the expression of Atg3, Atg12 and Beclin1 in the islet βcells of type 2 diabetic mice.
