双水杨酸酯通过抑制内质网应激缓解高脂饮食小鼠的高血糖状态  

Salsalate alleviates hyperglycemia by inhibiting endoplasmic reticulum stress in high fat diet induced obese mice

作　　者：袁心露[1] 聂丽 盖领[2] 姚宁华[2] 顾云娟[1] 朱晓晖[1] 孙诚[3] 崔世维[1] 

机构地区：[1]南通大学附属医院内分泌科,南通226001 [2]南通大学附属医院肿瘤科,南通226001 [3]南通大学江苏省神经再生重点实验室,南通226001

出　　处：《第二军医大学学报》2018年第2期220-225,共6页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81471037);江苏省南通市科技项目课题(MS22015126;MS22016071;HS2014036;HS2013024)~~

摘　　要：目的探讨双水杨酸酯(SAL)对高脂饮食喂养的小鼠血糖水平的影响。方法高脂饮食联合0.5%SAL(SAL组,n=5)或联合生理盐水(对照组,n=5)饲养8周龄C57BL/6J雄性小鼠40 d,行胰岛素耐量试验(ITT)和葡萄糖耐量试验(GTT),提取肝脏总RNA和蛋白,用q PCR和蛋白质印迹法检测内质网应激相关蛋白CCAAT增强子结合蛋白同源蛋白(CHOP)、内质网Dna J同系物4(ERDJ4)、葡萄糖调节蛋白(GRP)78和GRP94的表达水平。结果 SAL组小鼠随机血糖水平低于对照组(P<0.05),并且GTT提示糖耐量更好,但2组空腹胰岛素水平差异无统计学意义;ITT提示2组胰岛素刺激后血糖变化未见明显差异。SAL组小鼠肝脏组织GRP78和GRP94的m RNA表达水平也均较对照组低(P均<0.05),SAL组小鼠肝脏组织CHOP、ERDJ4、GRP78和GRP94的蛋白表达水平均较对照组低(P<0.05或P<0.01)。结论 SAL通过抑制内质网应激通路缓解高脂饮食小鼠的高血糖状态,并且这一过程不依赖于胰岛素作用。Objective To explore the effect of salsalate on the glucose metabolism of obese mice induced with high fat diet（HFD）. Methods Eight week-old male C57 BL/6 J mice were fed with HFD in combination with 0.5% of salsalate（SAL group, n=5） or normal saline（control group, n=5） for 40 days. The effect of salsalate on serum glucose level was examined by glucose tolerance test（GTT） and insulin tolerance test（ITT）. The expressions of endoplasmic reticulumn related proteins, including CCAAT/enhancer-binding protein homologous protein（CHOP）, endoplasmic reticulumlocalized Dna J 4（ERDJ4）, glucose regulated protein（GRP）78 and GRP94, were measured by q PCR and Western blotting. Results The random blood glucose level of obese mice were significantly lower in the SAL group than that in the control group（P0.05）, and GTT showed that the mice in the SAL group had better glucose tolerance. However, there was no significant difference in fasting insulin level between the two groups. ITT showed there was no difference in the change of blood glucose after insulin stimulation between the two groups. The m RNA expressions of GRP78 and GRP94 and protein expressions of CHOP, ERDJ4, GRP78 and GRP94 were significantly lower in the SAL group than those in the control group（P0.05 or P0.01）. Conclusion Salsalate can alleviate the hyperglycemia of obese mice induced with HFD by inhibiting endoplasmic reticulum stress, and the effect is independent of the insulin secretion.

关 键 词：糖尿病 高脂饮食 双水杨酸酯 内质网应激 胰岛素 血糖 

分 类 号：R362[医药卫生—病理学]