异搏定通过抑制TXNIP介导的细胞凋亡和炎症减轻高脂喂养小鼠的糖尿病前期神经病变  

Isoprofen Reduces Pre-diabetic Neuropathy in High-fat-fed Mice by Inhibiting TXNIP-mediated Apoptosis and Inflammation

作　　者：叶婷[1] 阿克拜尔·乌普[1] 岳薇薇 马丽[1] Ye Ting;Akebaier·Wupu;Yue Weiwei(Department of Endocrinology,Affiliated Hospital of Traditional Chinese Medicine,Xinjiang Medical University,Xinjiang 830001,China)

机构地区：[1]新疆医科大学附属中医医院内分泌科,乌鲁木齐830001

出　　处：《医学研究杂志》2020年第4期113-117,共5页Journal of Medical Research

基　　金：新疆维吾尔自治区自然科学基金资助项目(2018D01C020)。

摘　　要：目的探究异搏定对糖尿病小鼠前期神经病变的影响及机制。方法30只C57BL/6小鼠分为对照组、模型组和异搏定组,模型组和异搏定组高脂喂养构建糖尿病前期神经病变模型,给药治疗30天,给药期间监测血糖变化;给药结束后检测各组小鼠坐骨神经传导速度;HE染色观察坐骨神经组织病理变化;Elisa和RT-qPCR分别检测小鼠血清和坐骨神经组织中TNF-α、IL-1β、IL-6表达水平;原位缺口末端转移酶标记法(TUNEL)检测各组小鼠坐骨神经细胞凋亡;Western blot法检测各组小鼠坐骨神经组织TXNIP和NLRP3表达水平。结果相比于模型组,异搏定组小鼠给药期间血糖水平显著下降(P<0.05),坐骨神经组织病变显著改善,血清和坐骨神经组织中TNF-α、IL-1β、IL-6表达水平显著下降(P<0.05),细胞凋亡率显著下降(P<0.05);TXNIP和NLRP3表达显著下调(P<0.05)。结论异搏定能够缓解高脂喂养小鼠的糖尿病前期神经病变,其机制为抑制TXNIP的表达而调控炎性反应及细胞凋亡。Objective To investigate the effect and mechanism of verapamil on neuropathy in diabetic mice.Methods Thirty C57BL/6 mice were divided into control group,model group and Isoprofen group.Model group and Isoprofen group were fed with high-fat diet to construct pre-diabetic neuropathy model.The drug was treated for 30 days.After the end of drug administration,the sciatic nerve conduction velocity of each group was detected.HE staining was used to observe the pathological changes of sciatic nerve tissue.Elisa and RT-qPCR were used to detect the expression levels of TNF-α,IL-1βand IL-6 in mouse serum and sciatic nerve tissue,respectively.In situ nick end transferase labeling(TUNEL)was used to detect the apoptosis of sciatic nerve cells in each group.The expression of TXNIP and NLRP3 in sciatic nerve tissues of each group was detected by Western blot.Results Compared with the model group,the blood glucose level of the mice in the Isoprofen group decreased significantly(P<0.05),the lesions of the sciatic nerve tissue were significantly improved,and the expression levels of TNF-α,IL-1βand IL-6 in serum and sciatic nerve tissues were compared.Significantly decreased(P<0.05),apoptosis rate decreased significantly(P<0.05).TXNIP and NLRP3 expression were significantly down-regulated(P<0.05).Conclusion Isoprofen can alleviate pre-diabetic neuropathy in high-fat-fed mice by inhibiting the expression of TXNIP and regulating inflammation and apoptosis.

关 键 词：糖尿病 神经病变 炎症 细胞凋亡 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]