摘要
目的研究口服Rho激酶抑制药(FSD-C10)对实验性自身免疫性脑脊髓炎(EAE)小鼠的作用及其在氧化应激方面的作用机制。方法用髓鞘少突胶质细胞糖蛋白35-55免疫C57BL/6雌鼠建立EAE模型。按照体重将小鼠随机分为2组:模型组和实验组,每组8只。于免疫后第3天开始,实验组小鼠灌胃给予FSD-C10(50 mg·kg^(-1)﹒d^(-1)),连续给药25 d;模型组小鼠灌胃等体积生理盐水。记录小鼠的临床评分,第28天处死小鼠,用固蓝染色检测脊髓脱髓鞘程度;用蛋白质印迹技术检测过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平(灰度值),比色法检测脑组织中谷胱甘肽(GSH)和丙二醛(MDA)的含量。结果模型组和实验组的平均起病时间分别为(10.63±0.92)和(12.88±0.64)d;2组的累计临床评分分别为(22.69±1.25)和(12.25±1.56)分;2组的脊髓脱髓鞘占比分别为(34.68±4.94)%和(16.46±1.44)%;2组的CAT分别为0.47±0.06和0.72±0.04;2组的SOD分别为0.66±0.08和1.02±0.05;2组的GSH分别为(16.61±0.86)和(27.64±1.10)μmol·mg^(-1);2组的MDA分别为(1.40±0.28)和(0.58±0.12)nmol·mg^(-1)。上述指标:实验组与模型组相比,差异均有统计学意义(均P<0.01)。结论FSD-C10口服对EAE具有明确的治疗作用,其作用机制可能与恢复氧化—抗氧化体系平衡、抑制炎性反应有关。
Objective To explaor the effect and the antioxidant mechanism of oral administration of Rho kinase inhibitor(FSD-C10)on experimental autoimmune encephalomyelitis mice(EAE)in mice.Methods C57 BL/6 female mice were induced by myelin oligodendrocyte glycoprotein 35-55 to establish EAE model.Successful mouse model were randomly divided into model group(n=8)and experimental group(n=8)according to weight.Mice in the experimental group were intragastrically infused with FSD-C1050 mg·kg^(-1)·d^(-1)from the 3rd day to the 27th day after immunization.Mice in EAE group were treated with the same dosage of physiological saline,for 25 d.The clinical score of mice were recorded every other day.On the 28th day,mice were killed.The demyelination of spinal cord were detected by luxol fast blue staining.The levels(gray value)of catalase(CAT),superoxide dismutase(SOD)were detected by Western blotting.The content of glutathione(GSH)and malonaldehyde(MDA)in the brains were detected by colorimetry.Results The average onset time in model group and experimental group respectively were(10.63±0.92),(12.88±0.64)d;the cumulative score in the above 2 groups respectively were(22.69±1.25),(12.25±1.56)point;the demyelination in the above 2 groups respectively were(34.68±4.94)%,(16.46±1.44)%;the expression of CAT in the above 2 groups respectively were 0.47±0.06,0.72±0.04;the expression of SOD in the above 2 groups respectively were0.66±0.08,1.02±0.05;the content of GSH in the above 2 groups respectively were(16.61±0.86),(27.64±1.10)μmol·mg^(-1);the content of MDA in the above 2 groups respectively were(1.40±0.28),(0.58±0.12)nmol·mg^(-1).Comparing between experimental group and model group,the difference of the factors were significant(all P<0.01).Conclusion Oral delivery of FSD-C10,shows effectiveness in treating EAE,which may be related to restoring the balance of oxidation-antioxidant system and inhibiting inflammatory reaction.
作者
樊慧杰
柴智
李艳荣
刘建春
杨婵娟
殷福栋
王新亮
郭敏芳
肖保国
马存根
FAN Hui-jie;CHAI Zhi;LI Yan-rong;LIU Jian-chun;YANG Chan-juan;YIN Fu-dong;WANG Xin-liang;GUO Min-fang;XIAO Bao-guo;MA Cun-gen(Neurobiology Research Center,The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi Province,China;Institute of Brain Science,Shanxi Datong University,Datong 037009,Shanxi Province.China;Institute of Neurology,Huashan Hospital,Fudan University,Shanghai 200025,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第5期548-551,555,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金面上基金资助项目(81703978,81473577,81102552)
山西省国际科技合作基金资助项目(201703D421016)
山西省重点研发计划基金资助项目(201803D31091,201803D31209)
山西省青年拔尖人才支持计划基金资助项目(晋组办字[2019]35号文)
山西省自然科学基金资助项目(201901D111334)
山西省回国留学人员科研资助重点基金资助项目(2014-7,2017-129)
山西省留学人员科技活动项目择优基金资助项目([2017]19号文)
山西省高等学校科技创新计划基金资助项目(2019L0724)
基于炎症反应的重大疾病创新药物山西省重点实验室开放课题基金资助项目(SXIDL-2018-04)
山西中医药大学中西医结合防治神经系统疾病研究科技创新团队基金资助项目(2018TD-012)。
