摘要
目的探讨白细胞介素17A(interleukin 17A,IL-17A)对1型糖尿病(type 1 diabetes mellitus,T1DM)模型Ins2^(Akita)(Akita)小鼠海马神经炎症的影响。方法雄性Akita、IL-17A^(-/-)Akita以及同窝出生的野生型C57BL/6小鼠分别作为T1DM模型组,IL-17A缺陷T1DM模型组和正常对照组。ELISA检测IL-17A含量;血糖仪检测小鼠血糖,天平称量小鼠体质量;免疫荧光组织化学染色检测Iba-1阳性激活小胶质细胞形态及数量,NeuN和TUNEL双染检测神经元凋亡;Real-time PCR检测TNF-α基因表达水平;Western blot法检测CD11b、TNF-α、cleaved-caspase3蛋白表达水平。结果糖尿病小鼠血糖较野生小鼠明显升高、体质量下降,小胶质细胞激活数目明显增多,CD11b蛋白表达增高,TNF-α基因和蛋白表达水平增高,cleaved-caspase3蛋白表达水平升高;而IL-17A缺陷糖尿病小鼠较糖尿病小鼠血糖下降、体质量增加,小胶质细胞激活数目下降,CD11b蛋白表达下降,海马TNF-α基因和蛋白表达水平下降,cleaved-caspase3蛋白表达水平下降。结论 IL-17A缺陷可减轻T1DM小鼠海马小胶质细胞激活促发的神经炎症,进一步减少神经元凋亡。
In recent years, more and more attention has been paid to the involvement of IL-17A in diabetes.Our purpose is to investigate the effects of IL-17A in neuroinflammation of hippocampus in type 1 diabetes mellitus(T1DM) Ins2^Akitamice. Male Akita, IL-17A-/-Akita and wide-type mice from the same litter were selected as T1DM group, IL-17A deficiency T1DM group and control group. ELISA was used to detect the content of IL-17A;the blood glucose and weight of mice were detected by the blood glucose meter and balance, respectively;immunofluorescence histochemical staining was used to detect the morphology and number of Iba-1 positive activated microglia, and apoptosis ratio of neuron. Real-time PCR was used to detect the mRNA expression of TNF-α;Western blot analysis was employed to examine the expression of CD11 b, TNF-α and cleaved-caspase3. Data showed that in T1DM mice, the blood glucose was increased, the weight was decreased, the expression of TNF-αand Cleaved-caspase3 were increased and the number of activated microglia and the apoptosis rate of neuron were increased significantly. While in IL-17A deficiency T1DM mice, the blood glucose was decreased, the weight was increased, the number of activated microglia, the expression of CD11b, TNF-α and cleaved-caspase-3 and the apoptosis of neuron were decreased, compared with T1DM group. These combined data suggested that IL-17A deficiency alleviates the neuroinflammation induced by microglial activation in the hippocampus of T1DM mice.
作者
方小霞
刘金虎
翟小润
陈亚春
邱一华
彭聿平
FANG Xiaoxia;LIU Jinhu;ZHAI Xiaorun;CHEN Yachun;QIU Yihua;PENG Yuping(Department of Physiology,School of Medicine,Nantong University,Nantong 226001,China;Function Laboratory,School of Medicine,Nantong University,Nantong 226001,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2019年第4期308-314,共7页
Immunological Journal
基金
国家自然科学基金面上项目(31771293)
江苏省研究生科研与创新计划(KYCX18_2399)
江苏省高校自然科学面上项目(18KJD310003)
关键词
IL-17A
1型糖尿病
海马
神经炎症
IL-17A
Type 1 diabetes mellitus
Hippocampus
Neuroinflammation