盐酸小檗碱对颅脑创伤模型小鼠双侧丘脑继发性损伤的神经保护作用  

Protective effect of berberine chloride on secondary damage of bilateral thalami in traumatic brain injury model mice

作　　者：黄树宣 朱飞奇[1,3] 裴中[4] 邓旭辉[1] 杨志[1] 朱瑾华[1] 陈淳淳[1] 林伟丰[1] HUANG Shu-xuan ZHU Fei-qi PEI Zhong DENG Xu-hui YANG Zhi ZHU Jin-hua CHEN Chun- chun LIN Wei-feng(Department of Neurology, Yuebei People＇s Hospital Affiliated to Shantou University Medical College, Shaoguan 512026, Guangdong, China Department of Neurology, the First Affiliated Hospital, Sun Yat- sen University, Guangzhou 510080, Guangdong, China)

机构地区：[1]汕头大学医学院附属粤北人民医院神经内科,韶关512026 [2]广州医科大学附属第一医院神经内科,邮政骗码510080 [3]广东省深圳市罗湖区人民医院神经内科,邮政编码518001 [4]中山大学附属第一医院神经科,广州510080

出　　处：《中国现代神经疾病杂志》2017年第4期282-289,共8页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：广东省自然科学基金资助项目(项目编号:S2013010015786);广东省韶关市科技计划项目[项目编号:韶科(卫)2010-01]~~

摘　　要：目的探讨盐酸小檗碱对颅脑创伤(TBI)模型小鼠双侧丘脑继发性损伤(炎症反应、氧化损伤和神经元缺失)的神经保护作用。方法采用自由落体撞击法制备颅脑创伤模型,盐酸小檗碱组小鼠予以盐酸小檗碱50 mg/(kg·d)灌胃21 d,TBI组予等量生理盐水灌胃21 d,对照组不予自由落体撞击。免疫组织化学染色计数双侧丘脑诱导型一氧化氮合酶(i NOS)、环氧合酶-2(COX-2)、8-羟基脱氧鸟苷(8-OHd G)和神经元核抗原(Neu N)阳性神经元或胶质细胞数目,免疫荧光染色计数双侧丘脑胶质纤维酸性蛋白(GFAP)阳性星形胶质细胞和离子钙结合蛋白1(Iba1)阳性小胶质细胞数目。结果 3组小鼠颅脑创伤同侧丘脑i NOS(P=0.015)、COX-2(P=0.022)、8-OHd G(P=0.000)和Neu N(P=0.000)阳性神经元或胶质细胞数目以及GFAP阳性星形胶质细胞数目(P=0.024)和Iba1阳性小胶质细胞数目(P=0.000)差异均有统计学意义,其中,TBI组i NOS(P=0.005)、COX-2(P=0.011)和8-OHd G(P=0.000)阳性神经元或胶质细胞数目以及GFAP阳性星形胶质细胞数目(P=0.011)和Iba1阳性小胶质细胞数目(P=0.000)均高于对照组,而Neu N阳性神经元数目低于对照组(P=0.000);盐酸小檗碱组i NOS(P=0.031)、COX-2(P=0.024)和8-OHd G(P=0.008)阳性神经元或胶质细胞数目以及GFAP阳性星形胶质细胞数目(P=0.031)和Iba1阳性小胶质细胞数目(P=0.012)均低于TBI组,仅8-OHd G阳性神经元数目(P=0.014)和Iba1阳性小胶质细胞数目(P=0.024)仍高于对照组,而Neu N阳性神经元数目高于TBI组(P=0.016)、仍低于对照组(P=0.027)。3组小鼠颅脑创伤对侧丘脑仅COX-2(P=0.029)和8-OHd G(P=0.000)阳性神经元或胶质细胞数目差异有统计学意义,其中,TBI组COX-2(P=0.011)和8-OHd G(P=0.000)阳性神经元或胶质细胞数目高于对照组,盐酸小檗碱组COX-2(P=0.047)和8-OHd G(P=0.010)阳性神经元或胶质细胞数目低于TBI组,仅8-OHd G阳性神经元数目仍高于对照组(P=0.004)。结论颅脑创伤可以引Objective To investigate the protective effect of berberine chloride on secondary damage （inflammation, oxidative damage and neuron loss） in bilateral thalami of traumatic brain injury （TBI） model mice. Methods Mice were randomly divided into 3 groups： control group （N = 6）, TBI group （N = 6） and berberine group （N = 6）. TBI model was established by a free-falling hitting device. In control group, mice were not given free-falling hitting. Mice in berberine group were given a gavage of berberine chloride [50 mg/（kg, d）] for 21 d, while mice in TBI group were given the same dosage of normal saline for 21 d. Immunohistochemistry was used to count the number of neurons or gliocytcs positive for inducible nitric oxide synthase （iNOS）, eyclooxygcnase-2 （COX-2）, 8-hydroxy deoxyguanosine （8-OHdG） and neuronal nuclei （NeuN）, the number of astrocytes positive for glial fibrillary acidic protein （GFAP） and the number of microglias positive for ionized calcium- binding adaptor molecule 1 （Ibal）. Results The number of neurons or gliocytes positive for iNOS （P = 0.015）, COX-2 （P = 0.022）, 8-OHdG （P=0.000） and NeuN （P = 0.000）, the number of astrocytes positive for GFAP （P = 0.024） and microglias positive for Ibal （P = 0.000） in TBI ipsilateral thalamus were significantly different among 3 groups. In TBI group, the number of neurons or gliocytes positive for iNOS （P = 0.005）, COX-2 （P = 0.011） and 8-OHdG （P = 0.000）, the number of astrocytes positive for GFAP （P = 0.011） and microglias positive for Ibal （P = 0.000） were significantly higher than those in control group, while the number of neurons positive for NcuN （P = 0.000） was significantly lower than that in control group. In berberinc group, the number of neurons or gliocytes positive for iNOS （P = 0.031）, COX-2 （P = 0.024） and 8-OHdG （P=0.008）, the number of astroeytes positive for GFAP （P = 0.031） and microglias positive for Ibal （P = 0.012） were signific

关 键 词：小檗碱 颅脑损伤 丘脑 炎症 氧化性应激 神经元 疾病模型 动物 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]