水苏碱对局灶性脑缺血再灌注小鼠的保护作用及其机制  

Protective effects and its mechanism of stachydrine on focal cerebral ischemia reperfusion injury in mice

作　　者：刘保松 白明[1] 彭孟凡 李瑞奇 刘田园 苗明三[1] LIU Bao-song;BAI Ming;PENG Meng-fan;LI Rui-qi;LIU Tian-yuan;MIAO Ming-san(College of Pharmacy,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,郑州450046

出　　处：《中国临床药理学杂志》2018年第19期2295-2298,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家重大新药创制基金资助项目(2009ZX09103-324);河南省科技攻关基金资助项目(152102310103;152102410049)

摘　　要：目的研究水苏碱对局灶性脑缺血再灌注小鼠模型的保护机制。方法按照体重将小鼠随机分为6组:假手术组﹑模型组、对照组和低、中、高3个剂量实验组,每组16只。高、中、低3个剂量实验组灌胃水苏碱60,30,15 mg·kg^(-1)·d^(-1);对照组灌胃尼莫地平片30 mg·kg^(-1)·d^(-1);假手术组﹑模型组给予同体积0.9%NaCl。连续灌胃7 d后,通过线栓法制备脑缺血再灌注模型。造模再灌注22 h后,以酶联免疫吸附法测定小鼠脑匀浆Bcl-2相关X蛋白(Bax)、半胱氨酸蛋白酶3(Caspase-3)与B细胞淋巴瘤因子2(Bcl-2)和腺苷三磷酸(ATP)酶活性。结果模型组、对照组和高、中、低3个剂量实验组的Bax表达水平分别为(4.00±0.51),(2.84±0.48),(2.87±0.41),(2.92±0.46),(3.12±0.59)ng·mL^(-1);这5组的Caspase-3表达水平分别为(13.43±0.87),(9.95±1.57),(10.02±1.55),(10.58±1.48),(10.79±1.69)pmol·L^(-1);这5组的Bcl-2表达水平分别为(11.94±1.40),(16.14±1.33),(15.89±1.45),(15.31±1.20),(14.78±1.17)ng·mL^(-1),对照组和高、中、低3个剂量实验组与模型组比较,Bax、Caspase-3表达均显著减少而Bcl-2表达均显著升高,差异均有统计学意义(均P<0.01)。模型组、对照组和高、中、低3个剂量实验组的Na^+-K^+-ATP酶活力分别为(2.82±0.56),(4.84±1.61),(4.81±1.48),(4.50±1.22),(4.13±1.17)μmol Pi·mg^(-1)·h^(-1);这5组的Mg^(2+)-ATP酶活力分别为(2.55±0.56),(5.25±1.86),(5.15±2.37),(4.62±1.89),(4.13±1.54)μmol Pi·mg^(-1)·h^(-1),以上指标给药组与模型组相比较,差异均有统计学意义(P<0.05或P<0.01)。结论水苏碱可减轻小鼠局灶性脑缺血再灌注损伤,其机制可能与改善能量代谢障碍、减少细胞凋亡与改善脑部微循环有关。Objective To explore the protective effects and its mechanism of stachydrine on focal cerebral ischemia reperfusion injury in mice.Methods The focal cerebral ischemia reperfusion injury model in mice was established by thread method. KM mice were randomly divided into 6 groups（ n = 16） ： sham operation group,model group,control group,experimental-L,experimental-M,experimental-H groups,mice in each group were given related drugs via intragastric administration before the operation,once a day,lasting for 7 d. Reperime 22 h,the levels of Caspase-3,B-cell lymphoma-2（ Bcl-2）,B-lymphoma-2 gene-related X protein（ Bax） and adenosine triphosphate（ ATP） enzymeactivity in each group was detected by enzyme linked immunosorbent assay. Results The relative expression of Bax in model group,control group,experimental-L,experimental-M,experimental-H groups were（ 4. 00 ± 0. 51）,（ 2. 84 ± 0. 48）,（ 2. 87 ± 0. 41）,（ 2. 92 ± 0. 46）,（ 3. 12 ± 0. 59） ng·mL^-1,respectively; the relative expression of Caspase-3 in the 5 groups were（ 13. 43 ± 0. 87）,（ 9. 95 ± 1. 57）,（ 10. 02 ± 1. 55）,（ 10. 58 ± 1. 48）,（ 10. 79 ± 1. 69）pmol·L^-1,respectively; the relative expression of Bcl-2 in the 5 groups were（ 11. 94 ± 1. 40）,（ 16. 14 ± 1. 33）,（ 15. 89 ± 1. 45）,（ 15. 31 ± 1. 20）,（ 14. 78 ± 1. 17） ng·mL^-1,respectively; compared with the model group,the relative expressions of Bax and Caspase-3 in control group,three doses experimental groups markedly reduced while the relative expression of Bcl-2 in the 4 groups markedly increased significantly（ all P〈0. 01）. The Na^＋-K^＋-ATP enzyme activity in the model group,control group,experimental-L,experimental-M,experimental-H groups were（ 2. 82 ± 0. 56）,（ 4. 84 ± 1. 61）,（ 4. 81 ± 1. 48）,（ 4. 50 ± 1. 22）,（ 4. 13 ± 1. 17） μmol Pi·mg^-1·h^-1,respectively;and Mg^（2＋）-ATP enzyme activity in the 5 groups were（ 2. 55 ± 0. 56）,（ 5. 25 ± 1. 86）,（ 5. 15 ± 2. 37）,（ 4.

关 键 词：水苏碱 脑缺血再灌注 能量代谢 细胞凋亡 

分 类 号：R28[医药卫生—中药学]