王征,伍成文,陈豪,施森,曾宏,刘勇.二肽基肽酶-Ⅳ抑制剂通过激活ERK1/2和NF-κB信号通路促进2型糖尿病小鼠主动脉血管钙化[J].转化医学杂志,2019,8(3):144-148
二肽基肽酶-Ⅳ抑制剂通过激活ERK1/2和NF-κB信号通路促进2型糖尿病小鼠主动脉血管钙化
Study on DPP-4 in the promotion of aortic vascular calcification in type 2 diabetic mice by activating ERK1/2 and NF-κB signaling pathways
  
DOI:
中文关键词:  糖尿病小鼠  血管钙化  二肽基肽酶-Ⅳ  细胞外调节蛋白激酶  与kappa基因相结合的核因子
英文关键词:Diabetic mice  Vascular calcification  Dipeptidyl peptidase-4 (DPP-4)  Extracellular regulated protein kinases(ERK1/2)  Nuclear factor kappa gene binding (NF-κB)
基金项目:国家自然科学基金(81270358)
作者单位
王征 西南医科大学附属医院血管外科 
伍成文 西南医科大学附属医院血管外科 
陈豪 西南医科大学附属医院血管外科 
施森 西南医科大学附属医院血管外科 
曾宏 西南医科大学附属医院血管外科 
刘勇 西南医科大学附属医院血管外科 
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中文摘要:
      目的 探讨2型糖尿病小鼠发生主动脉血管钙化后,机体内二肽基肽酶-Ⅳ(dipeptidyl peptidase-4,DPP-4)、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK1/2)与kappa基因相结合的核因子(nuclear factor-kappa gene binding,NF-κB)等变化及相关机制的研究。方法 对正常小鼠(对照组)与糖尿病小鼠均进行高糖高脂饲料喂养,按照不同的给药方式进行分组治疗后,通过血液检测各组小鼠血糖及ELISA试剂盒检测各组小鼠DPP-4浓度变化,通过钙离子试剂盒测定主动脉中钙离子含量,通过Von Kossa钙化染色测定各组小鼠腹主动脉钙化情况,通过免疫组化与Western blot实验测定血管组织各蛋白的表达情况。结果与对照组比较,糖尿病组小鼠血糖含量、主动脉钙离子含量、DPP-4浓度及血管钙化程度均升高(P<0.05);与糖尿病组比较,西格列汀及各抑制剂组小鼠血糖含量、主动脉钙离子含量、DPP-4浓度及血管钙化程度均降低(P<0.05)。与对照组比较,糖尿病组p-ERK与NF-кB蛋白表达量显著增加(P<0.05);与糖尿病组比较,西格列汀及各抑制剂组p-ERK与NF-κB蛋白表达量显著减少(P<0.05)。结论 糖尿病小鼠体内DPP-4含量明显增多,从而激活ERK1/2与NF-κB信号通路,促进其主动脉血管发生钙化。
英文摘要:
      Objective To explore the changes of dipeptidyl peptidase-4 (DPP-4), extracellular regulated protein kinases(ERK1/2)and nuclear factor-kappa gene binding (NF-κB)in the body and the related mechanisms after aortic calcification in type 2 diabetic mice. Methods Both normal mice (control group) and diabetic mice were fed with high-glucose and high-fat fodder. The mice were divided into 6 groups according to different administration modes, the blood glucose of each group was detected by blood, and the concentration of DPP-4 in mice was detected by ELISA kits. Calcium ion kit was used to determine the calcium ion content in aorta. The abdominal aortic calcification in each group was determined by Von Kossa calcification staining. The expression levels of proteins in vascular tissues were determined by immunohistochemistry and Western blot. Results Compared with control group, the contents of blood glucose and aorta calcium ion, DPP-4 concentration and vascular calcification were significantly increased in diabetic mice group (P<0.05). Compared with diabetic mice group, the contents of blood glucose and aorta calcium ion, DPP-4 concentration and vascular calcification were significantly decreased in sitagliptin group and different inhibitors groups (P<0.05). The expression levels of p-ERK and NF-κB proteins were significantly increased in diabetic mice group compared with those in control group (P<0.05). The expression levels of p-ERK and NF-κB proteinw were significantly decreased in sitagliptin group and different inhibitors groups compared with those in diabetic mice group (P<0.05). ConclusionThe DPP-4 content in diabetic mice is significantly increased, thus activating ERK1/2 and NF-κB signaling pathways and promoting aortic vascular calcification.
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