摘要
目的研究人参皂苷Rg1对2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠神经元损伤的影响并探讨其潜在机制。方法雄性C57BL/6小鼠84只,随机分为7组:control组、HFD组、HFD+STZ组、Rg1(1、5、10 mg·kg^(-1))和二甲双胍治疗组。用高脂饮食(HFD)和链脲霉素(STZ)制备T2DM小鼠模型,成功后给予8周的药物治疗。水迷宫评估小鼠学习记忆能力,HE染色、β-半乳糖苷酶(β-Gal)染色、普鲁士蓝染色评估皮质和海马受损情况,免疫荧光检测脑内NEUN和NLRP1的共定位及表达,RT-PCR检测NLRP1相关mRNA水平,Western blot检测脑内NLRP1、MAPK相关蛋白的量。结果水迷宫实验表明,经过Rg1治疗的小鼠学习记忆能力明显提高。组织学染色表明,Rg1能够使T2DM小鼠的神经元损伤、衰老以及脑血管损伤明显改善。免疫荧光检测表明,Rg1治疗减少了T2DM小鼠脑内的NLRP1在NEUN阳性神经元的表达。Western blot和RT-PCR结果显示,Rg1治疗降低了T2DM小鼠脑内NLRP1、ASC,caspase-1、IL-1β,p-ERK、p-JNK、p-P38和p-GSK-3β等蛋白表达及NLRP1,ASC,caspase-1等mRNA水平。结论人参皂苷Rg1可以相对减少T2DM小鼠的神经元受损,其机制可能与抑制MAPK-NLRP1信号通路有关。
Aim To investigate the effects of ginsenoside Rg1 on learning memory and neuronal damage in mice with type 2 diabetes mellitus(T2DM)and to explore the underlying mechanisms.Methods Eighty-four male C57BL/6 mice were randomly divided into seven groups:Control,HFD,HFD+STZ,Rg1(1,5,10 mg·kg^(-1)),Metformin group.The T2DM mouse model was successfully prepared with high-fat diet(HFD)and streptozotocin(STZ)and administered for eight weeks.Morris water maze was used to assess the learning memory ability.HE,β-galactosidase(β-Gal)staining and Prussian blue staining were used to observe the pathological changes in hippocampus.Immunofluorescence was used to detect the expression of NEUN and NLRP1 in brain.RT-PCR was used to detect the level of NLRP1-related mRNA,and Western blot was used to detect the expression of NLRP1 and MAPK-related proteins in brain.Results Compared with the HFD+STZ group,the learning and memory ability of mice in the Rg1 groups were significantly improved,neuronal damage,aging and cerebral vascular damage were significantly improved,the expression of NLRP1 in NEUN-positive neurons was reduced,and the expression of NLRP1,IL-1β,p-ERK and other proteins and mRNA levels such as NLRP1,ASC,and caspase-1 in brain of mice were significantly reduced.Conclusions Rg1 treatment ameliorates cognitive dysfunction of T2DM mice,and the mechanism may involve inhibition of the MAPK-NLRP1 signaling pathway.
作者
黄蕾
汪燕燕
孙冉
周慧敏
姬朋敏
孔亮亮
李卫平
李维祖
HUANG Lei;WANG Yan-yan;SUN Ran;ZHOU Hui-min;JI Peng-min;KONG Liang-liang;LI Wei-ping;LI Wei-zu(Dept of Pharmacology,School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China;Dept of Pharmacy,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第11期2034-2042,共9页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81970630)
安徽省自然科学基金资助项目(No 2208085MH219)
安徽省高校自然科学研究重大项目(No KJ2020ZD14)。