左旋四氢巴马汀对局灶性脑缺血再灌注大鼠脑内肿瘤坏死因子-α白细胞介素-1β表达的影响  

Effects of L-tetrahydropalmatine on brain expressions of TNF-α and IL-1β in rats with focal cerebral ischemia-reperfusion

作　　者：陈鹏[1] 李斌[2] 弥曼[3] 

机构地区：[1]西安医学院生物化学与分子生物学教研室,710021 [2]西安医学院附属医院胸外肿瘤科 [3]西安医学院药理学教研室,710021

出　　处：《中国药物与临床》2010年第6期628-631,I0001,共5页Chinese Remedies & Clinics

基　　金：陕西省卫生厅2006年度自然科学基金(06018);西安医学院2006年度院扶植项目(2006FZ1)

摘　　要：目的探讨左旋四氢巴马汀(L-THP)对脑缺血再灌注损伤的保护机制。方法采用大脑中动脉阻塞法建立大鼠局灶性脑缺血再灌注模型。将90只SD大鼠随机分为空白对照组、假手术组、模型组(I-R)、L-THPI组(I-R+L-THP50mg/kg)、L-THPⅡ组(I-R+L-THP25mg/kg)、L-THPⅢ组(I-R+L-THP12.5mg/kg),每组又分为缺血3h再灌注3、6、24h。每组15只SD大鼠,每时间点5只SD大鼠。采用11分法分别对大鼠进行行为缺陷评分;采用免疫组织化学法测定肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β的表达。结果模型组各时间点神经行为学评分、TNF-α、IL-1β的表达均增加,数值6h较3h增高,24h最高,与3h相比差异有统计学意义(P<0.05)。L-THP各剂量组能明显改善上述指标,L-THP大、中剂量与模型组各时间点相比差异有统计学意义(P<0.05)。结论在脑缺血再灌注损伤24h内,以24h损伤更为严重。L-THP对脑保护作用可能与抑制炎症反应有关。Objective To study the mechanism by which L-tetrahydropalmatine （L-THP） affects brain expressions of TNF-α and IL-1β in rats with focal cerebral ischemia-reperfusion. Methods Model of focal cerebral ischemia reperfusion in rats was established by middle cerebral artery occlusion. Ninety healthy SD rats were randomly divided into six groups： control group, sham operation group, ischemia reperfusion model group （I-R group）, I-R＋50 mg/kg L-THP group （L-THP I group）, I-R＋25mg/kg LTHP group （L-THPⅡ group） and I-R＋15 mg/kg L-THP group （L-THPⅢ group）. Each group was further divided to receive 3, 6 and 24 h reperfusion after 3 h ischemia, and thus there were 15 SD rats in each group with 5 assigned to each time point. A 11-score system was used to evaluate behavioral deficit in rats. The expressions of TNF-α and IL-1β were measured with immunohistochemistry. Results In I-R group, increased neurological deficit scores, expressions of TNF-α and IL-1β at each time point were shown, with the values at 6 h higher than those at 3 h, and peaking at 24 h, as compared significantly with 3 h （P〈0.05）. These values were further improved with use of various L-THP dose. There were significant differences at each time point between high-or moderate-dose L-THP groups and the I-R group. Conclusion Cerebral ischemia-reperfusion injury may be the most severe at 24 h when first 24 h are concerned. The cerebral protection of L-THP might be associated with suppression of inflammatory reactions.

关 键 词：脑缺血 大鼠 炎症 左旋四氢巴马汀 

分 类 号：R741[医药卫生—神经病学与精神病学]