mfat-1基因疗法有效预防及治疗小鼠多发性硬化症  

mfat-1 gene therapy prevents and ameliorates multiple sclerosis in mice

作　　者：唐敏怡 毕欣耘 王帅 邢朝凤 吴晓丽 赵子建 李芳红 TANG Min-yi;BI Xin-yun;WANG Shuai;XING Chao-feng;WU Xiao-li;ZHAO Zi-jian;LI Fang-hong(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China;University of North Carolina at Chapel Hill,North Carolina 27599-3140,America;Shunde Hospital of Southern Medical University,Southern Medical University,Foshan Guangdong 528300,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006 [2]北卡罗来纳州立大学教堂山分校,北卡罗来纳州27599-3140 [3]南方医科大学顺德医院,广东佛山528300

出　　处：《中国药理学通报》2024年第10期1930-1936,共7页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划项目(No 2018YFA0800603);国家自然科学基金资助项目(No 82003615);广东省重点领域研发计划项目(No 2019B020201015);广州市科技计划项目(No 202201010147);广东省创新团队(No 2016ZT06Y432)。

摘　　要：目的 探讨mfat-1基因疗法对小鼠实验性自身免疫性脑脊髓炎的预防及治疗作用。方法 利用mfat-1基因治疗方法来提高小鼠体内内源性的ω-3多不饱和脂肪酸(polyunsaturated fatty acids, PUFAs)含量的同时,降低ω-6 PUFAs含量,改变ω-3/ω-6 PUFAs的比例,并使用气相色谱分析小鼠外周血中PUFAs的比例;运用小鼠神经功能障碍评分评估小鼠神经功能缺损情况;通过小鼠脊髓切片HE染色以及LFB染色观察中枢神经系统炎症浸润和脱髓鞘病变;利用流式细胞术微球芯片技术检测血清中细胞因子的含量。结果 mfat-1基因治疗能明显提高小鼠外周血ω-3/ω-6 PUFAs的比例(P<0.01);有效延缓实验性自身免疫性脑脊髓炎小鼠疾病高峰期,并明显降低神经功能障碍评分(P<0.05);改善小鼠中枢神经系统炎症浸润程度和神经髓鞘损伤(P<0.05);明显下调血清中的IL-2、IFN-γ、IL-4、IL-17的含量(P<0.05)。结论 利用mfat-1基因疗法提高外周血ω-3/ω-6PUFAs的比例能有效预防及治疗小鼠实验性自身免疫性脑脊髓炎。Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on experimental autoimmune encephalomyelitis in mice.Methods mfat-1 gene therapy was used to render the host endogenous capability of producingω-3 PUFAs,concomitantly reduce the levels ofω-6 PUFAs,and change the proportion ofω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to observe central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion ofω-3/ω-6 PUFAs(P<0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P<0.05),and improve inflammation and demyelination of spinal cords(P<0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P<0.05).Conclusion The proportion ofω-3/ω-6 PUFAs in blood circulation enhanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

关 键 词：mfat-1 基因治疗 Ω-3多不饱和脂肪酸 ω-6多不饱和脂肪酸 多发性硬化症 实验性自身免疫性脑脊髓炎 

分 类 号：R-332[医药卫生] R344.7R459.9R744.3R744.51