机构地区:[1]辽宁中医药大学,辽宁沈阳110847 [2]河北中医药大学,河北石家庄050200
出 处:《中国中医药信息杂志》2024年第6期80-87,共8页Chinese Journal of Information on Traditional Chinese Medicine
基 金:国家中医药管理局青年岐黄学者培养项目(2022年);辽宁省科学技术计划-应用基础研究计划(2022JH2/101300108、2023JH2/101300050);辽宁省中央引导地方科技发展专项(2019JH6/10200009);辽宁省教育厅高校基本科研项目(2023年);石岩教授辽宁省名中医传承工作室(2022年)。
摘 要:目的观察益糖康对db/db小鼠神经炎症及小胶质细胞和星形胶质细胞极化的调控作用,探讨其治疗糖尿病认知障碍的作用机制。方法32只db/db小鼠随机分为模型组、利拉鲁肽组和益糖康低、高剂量组,另取C57BL/6小鼠作为空白组,每组8只。益糖康低、高剂量组分别灌胃益糖康煎剂15、30g/kg,利拉鲁肽组腹腔注射利拉鲁肽200μg/kg,空白组和模型组予等量蒸馏水灌胃,连续5周。FJC染色观察海马神经元损伤情况,ELISA检测海马组织白细胞介素(IL)-6、IL-1β含量,免疫组化检测海马组织IL-6、IL-1β、离子钙结合衔接分子1(Iba1)和胶质纤维酸性蛋白(GFAP)表达,免疫荧光检测海马组织CD86、CD206、C3、S100A10、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、Iba1、GFAP表达,Westernblot检测海马组织CD86、CD206、C3、S100A10、NLRP3蛋白表达。结果与空白组比较,模型组小鼠海马组织FJC阳性细胞数显著增加,IL-6、IL-1β含量显著增加,Iba1、CD86、GFAP、C3表达显著升高,CD206、S100A10表达显著降低,NLRP3蛋白表达及Iba1/NLRP3、GFAP/NLRP3共表达显著升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,利拉鲁肽组和益糖康低、高剂量组小鼠海马组织FJC阳性细胞数显著减少,IL-6、IL-1β含量显著减少,Iba1、CD86、GFAP、C3表达显著降低,CD206、S100A10表达显著升高,NLRP3蛋白表达及Iba1/NLRP3、GFAP/NLRP3共表达显著降低,除益糖康低剂量组CD206外,差异均有统计学意义(P<0.05,P<0.01)。结论益糖康可有效调节db/db小鼠海马组织NLRP3表达,促进小胶质细胞/星形胶质细胞从M1/A1型向M2/A2型转化,抑制炎症反应,发挥神经保护作用。Objective To observe the regulatory effects of Yitangkang on neuroinflammation and polarization of microglia and astrocytes in db/db mice;To explore the its mechanism in the treatment of cognitive impairment in diabetes.Methods Totally 32 db/db mice were randomly divided into model group,liraglutide group,and Yitangkang low-and high-dosage group.Another C57BL/6 mice were taken as blank group,with 8 mice in each group.Yitangkang low-and high-dosage group were given Yitangkang Decoction 15,30 g/kg respectively,the liraglutide group was intraperitoneally injected with liraglutide 200μg/kg,the blank group and model group were given the same volume of distilled water by gavage,for 5 weeks.FJC staining was used to observe the damage of hippocampal neurons,ELISA was used to detect the content of IL-6 and IL-1βin hippocampal tissue,immunohistochemistry was used to detect the expressions of IL-6,IL-1β,Iba1 and GFAP in hippocampal tissue,the expressions of CD86,CD206,C3,S100A10,NLRP3,Iba1 and GFAP were detected by immunofluorescence,the protein expressions of CD86,CD206,C3,S100A10 and NLRP3 in hippocampal tissue were detected by Western blot.Results Compared with the blank group,the FJC positive cells in the model group significantly increased,and the contents of IL-6 and IL-1βsignificantly increased,the expressions of Iba1,CD86,GFAP and C3 significantly increased,CD206 and S100A10 expressions significantly decreased,NLRP3 protein expression and co-expression with Iba1 and GFAP significantly increased,with statistical significance(P<0.05,P<0.01).Compared with the model group,the FJC positive cells in hippocampal tissue of liraglutide group and Yitangkang low-and high-dosage group significantly decreased,the contents of IL-6 and IL-1βsignificantly decreased,the expressions of Iba1,CD86,GFAP and C3 significantly decreased,the expressions of CD206 and S100A10 significantly increased,the expression of NLRP3 protein and co-expression with Iba1 and GFAP were significantly decreased,the differences were statistically signifi
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