ω-3多不饱和脂肪酸促进1型糖尿病模型小鼠胰岛β细胞再生的作用研究  

Pancreaticβcell regeneration in type 1 diabetes mellitus through elevatingω-3 PUFAs

作　　者：邢朝凤 唐敏怡 徐绮华 张宗猛 封文斌 穆云萍 李芳红 赵子建 XING Chao-feng;TANG Min-yi;XU Qi-hua;ZHANG Zong-meng;FENG Wen-bin;MU Yun-ping;LI Fang-hong;ZHAO Zi-jian(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006

出　　处：《中国药理学通报》2023年第11期2141-2148,共8页Chinese Pharmacological Bulletin

基　　金：广东省重点领域研发计划项目(No 2019B020201015);广东省“珠江人才计划”项目(No 2016ZT06Y432);国家重点研发计划项目(No 2018YFA0800603)。

摘　　要：目的探讨ω-3多不饱和脂肪酸(ω-3 PUFAs)促进胰岛α细胞向β细胞转分化的作用。方法在小鼠胰岛α细胞系αTC1培养基中添加不同配比的ω-3 PUFAs,4周后,利用荧光染色观察胰岛素和胰高血糖素的表达,并通过荧光定量PCR(qRT-PCR)检测胰岛α细胞和胰岛β细胞特异性基因表达情况。野生型(WT)组和mfat-1转基因组小鼠连续5天腹腔注射60 mg·kg^(-1)链脲佐霉素(streptozocin,STZ)。选取注射STZ 7周后的WT小鼠,给予97%EPA和75%鱼油(50%EPA和25%DHA)饮食干预,每周检测随机血糖。8周后,通过免疫荧光染色观察小鼠胰腺中胰岛β细胞再生情况。结果在DHA与EPA混合液培养以及与单独EPA培养后,胰岛α细胞可分泌胰岛素,而对照组细胞没有胰岛素染色阳性;qRT-PCR结果显示,经过ω-3 PUFAs处理的细胞中,胰岛β细胞特异性基因明显上调。注射STZ后,mfat-1组和饮食干预组小鼠不仅随机血糖水平明显低于WT组,而且免疫荧光结果显示mfat-1组和饮食干预组小鼠胰岛中出现胰岛素和胰高血糖素共定位的细胞。结论初步证明ω-3 PUFAs能够促进胰岛α细胞分泌胰岛素,缓解1型糖尿病小鼠的高血糖症状。Aim To investigate the role of omega-3 polyunsaturated fatty acids(ω-3 PUFAs)in the transdifferentiation of pancreaticαcells toβcells in mice with type 1 diabetes mellitus.Methods A mouse pancreaticαcell line namedαTC1 was co-incubated in the culture medium with various doses ofω-3 PUFAs.The cells were immobilized and fluorescently labeled with antibodies against insulin and glucagon after being in culture for four weeks.The cells were also gathered for transcriptome analysis of the major signaling pathways in the trans-differentiation of pancreaticαcells toβcells,with the findings confirmed by qRT-PCR.60 mg·kg^(-1)streptozocin(STZ)was employed to trigger the death of pancreaticβcells in both wild-type and mfat-1 transgenic mice(a transgenic model capable of endogenous generation ofω-3 PUFAs)for five consecutive days.Following successful STZ-modeling,the wild-type mice were also given 97%EPA and 75%fish oil(50%EPA and 25%DHA)treatment.Blood glucose levels were monitored for the development of diabetes following the completion of STZ administration.After eight weeks of intervention,immunofluorescent staining was used to assess the regeneration of pancreaticβcells in pancreas of mice.Resultsαcells of pancreatic islets released insulin after being cultured with DHA and EPA or with EPA alone,but no insulin staining was seen in the control cells.qRT-PCR revealed that cell-specific genes were up-regulated in the cells treated withω-3 PUFAs.After STZ injection,mice in the mfat-1 group and the diet intervention group not only had random blood glucose levels that were noticeably lower than those in the WT group,but the immunofluorescence results also revealed the appearance of insulin and glucagon co-localized cells in pancreas of the mfat-1 group and diet intervention group mice.Conclusions It has been preliminarily demonstrated thatω-3 PUFAs can ameliorate type 1 diabetic mice with hyperglycemia symptoms by encouraging insulin production by pancreatic α cells.

关 键 词：Ω-3多不饱和脂肪酸 1型糖尿病 胰岛Α细胞 胰岛Β细胞 转分化 mfat-1转基因小鼠 

分 类 号：R-332[医药卫生] R322.57R344.7R587.1R977.6