缬沙坦预先给药对小鼠局灶性脑缺血再灌注损伤的保护作用  

Protective effects of valsartan pretreatment against focal cerebral ischemia-reperfusion injury in mice

作　　者：曹阳 冯红斌 缪海生 周俊岭[3] 胡琼玉 陈月芳 岳云[4] 

机构地区：[1]南方医科大学药理学系,广州市510566 [2]广州市第六人民医院麻醉科 [3]南方医科大学中心实验室,广州市510566 [4]首都医科大学北京朝阳医院

出　　处：《中华麻醉学杂志》2005年第7期536-539,共4页Chinese Journal of Anesthesiology

基　　金：广东省卫生科研基金资助项目(A2004557)广州市医药卫生科研项目(2004050)

摘　　要：目的探讨血管紧张素Ⅱ1型受体(AT1)阻断剂缬沙坦预先给药对小鼠脑缺血再灌注损伤的保护作用。方法36只雄性C57BL/6J小鼠随机分为两组,每组18只,处理组(V组)将缬沙坦溶于2.5%NaHCO3 100μl,以微量注射泵2 mg·kg-1·d-1泵入腹腔至实验结束,对照组(C组)仅予2.5% NaHCO3 100μl在相同时间以相同速率泵注。给药第10天以线栓法建立局灶性脑缺血再灌注损伤模型,缺血1 h后拔出线栓,再灌注23 h。以激光多普勒血流探测仪测定缺血前10 min、缺血即刻、缺血10、30、50 min、再灌注10、30、60 min时的局部脑血流。在应用缬沙坦前即刻、缺血前10 min、再灌注10min用尾袖法测量平均动脉压。再灌注23 h后行神经功能损害评分。处死小鼠后,测定脑梗塞灶面积和脑含水量。结果两组小鼠3个时点的平均动脉压比较差异无统计学意义(P>0.05)。与C 组比较,V组脑梗塞灶面积减小,死亡率降低,神经功能损害评分降低,脑含水量减少,再灌注后V组梗塞灶中央区和半暗区局部脑血流升高(P<0.05)。结论预先应用AT1受体阻断剂缬沙坦可改善局部脑血流,减轻小鼠局灶性脑缺血再灌注损伤。Objective To investigate the protective effects of pretreatment with valsartan, an angiotensin Ⅱ type 1 receptor blocker, on the brain against ischemia-reperfusion （I/R） injury. Methods Thirty-six healthy male C57BL/6J mice aged 10-12 weeks weighing 20-25 g were randomlv divided into 2 groups （ n = 18 each） ： valsartan group （Ⅴ） and control group （C）. In group Ⅴ valsartan 2 mg·kg^-1 dissolved in 2.5% NaHCO3 100μ1 was given intraperitoneally （i. p. ） every day for 10 days before experiment while in group C 2.5 % NaHCO3 100 μl without valsartan was given. The animals were anesthetized with intraperitoneal pentobarbital 40 mg·kg^-1 . Middle cerebral artery, occlusion （MCAO） was produced by inserting an 8-0 nylon thread with rounded end into the left internal carotid artery and advancing it cranially until resistance was felt. MCAO was maintained for 1 h. The nylon thread was then withdrawn for reperfusion. A laser doppler blood flow detector （Omegaflo FLO-C1 , Omegawave Co, Netherlands） was used to detect local cerebral blood flow （LCBF） at central and marginal infarct area [ LCBF （ % ） = LCBF during I/R / baseline LCBF × 100% ]. The model of MCAO was considered established when LCBF at central infarct area was 20% lower than the baseline value. LCBF was measured 10 rain before MCAO （To , baseline）, as soon as MCA Was occluded （T1 ） at 10, 30, 50 min of ischemia （T24） and at 10, 30, 60 min of reperfusion （T5-7 ）. MAP was measured immediately before valsartan administration, at T0 and T5. Neurological function deficit （NFD） was evaluated and scored （0 = no deficit, 4 = worst result） at 23 h after reperfusion was started . After evaluation of NFD the animals were anesthetized again and killed. The brains were removed. Cerebral water content was measured [ cerebral water content （ % ） = （wet weight - dry weight） / wet weight × 100% ]. Infarct area was measured. Mortality rate was recorded. Results Pretreatment with valsartan did not affe

关 键 词：缬沙坦 预先给药 小鼠 局灶性脑缺血再灌注损伤 保护作用 脑血流 

分 类 号：R965[医药卫生—药理学]