摘要
目的:探讨究丹参酮ⅡA(TanⅡA)对CC类趋化因子配体2(CCL2)所致大鼠认知功能障碍的改善作用及其机制。方法:将56只雄性SD大鼠随机分为7组:空白对照组、假手术组、模型组(5 ng CCL2)、美金刚组(10 mg/kg·d^-1)、TanⅡA低(25 mg/kg·d^-1)、中(50 mg/kg·d^-1)、高(75 mg/kg·d^-1)剂量组,每组8只。除空白对照组外,其余各组均经双侧海马注射相应药物。造模完成后采用Morris水迷宫检测大鼠学习记忆能力,苏木精—伊红(HE)染色观察海马神经元形态学,并检测海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力以及丙二醛(MDA)含量,实时荧光定量PCR(qPCR)法测定caspase-3、caspase-8、caspase-9 mRNA相对表达量。结果:与模型组比较,TanⅡA低、中、高剂量组大鼠逃避潜伏期缩短,游泳路程减少,穿越平台次数增加,海马组织SOD和GSH-Px活性升高,而MDA含量及caspase-3、caspase-8、caspase-9 mRNA相对表达量均显著降低(均P<0.05)。HE染色显示,TanⅡA能够改善认知障碍大鼠海马组织病理损伤情况。结论:TanⅡA能减轻CCL2对大鼠海马造成的认知功能和学习记忆损害,改善大鼠认知功能,其机制与抗氧化、抑制神经细胞凋亡有关。
Objective:To investigate the effect and mechanisms of tanshinone(Tan)ⅡA on CC chemokine ligand 2(CCL2)-induced cognitive dysfunction in rats.Methods:A total of 56 male SD rats were randomly divided into 7 groups:control group,sham group,model group,memantine group(10 mg/kg d-1),and TanⅡA low-dose,middle-dose and high-dose groups(25,50,75 mg/kg d-1).All rats received bilateral hippocampal injection except for the control group.The learning and memory abilities of rats were detected by Morris water maze.The morphology of the hippocampal neurons was observed by hematoxylin-eosin(HE)staining.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and the content of malondialdehyde(MDA)in hippocampus were measured.The mRNA expressions of caspase-3,caspase-8 and caspase-9 were determined by qPCR.Results:Compared with the model group,the escape latency and swimming distance in TanⅡA-treatment groups were reduced,the platform crossing times and the activities of SOD and GSH-Px were increased,while the content of MDA and the mRNA expression levels of caspase-3,caspase-8 and caspase-9 were decreased.HE staining showed that TanⅡA could improve the pathological condition of hippocampus in rats with cognitive impairment.Conclusion:TanⅡA could attenuate learning memory and cognition impairment induced by CCL2,and the mechanisms might involve in anti-oxidation and anti-apoptosis.
作者
廖苑君
陈健民
龙江宜
周怡俊
梁冰玉
周燕
Liao Yuanjun;Chen Jianmin;Long Jiangyi;Zhou Yijun;Liang Bingyu;Zhou Yan(Department of Pharmacology,Guangxi Medical University,Nanning 530021,China;Guangxi Key Laboratory of AIDS Prevention and Treatment,School of Public Health,Guangxi Medical University,Nanning 530021,China)
出处
《广西医科大学学报》
CAS
2019年第11期1713-1718,共6页
Journal of Guangxi Medical University
基金
国家自然科学基金资助项目（No.81660213
No.81360192）
广西自然科学基金资助项目（No.2017GXNSFAA198187
No.2018GXNSFAA281325）
广西一流学科（药学）建设课题资助项目（No.GXFCDP-PS-2018）
