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 MCAO was maintained for 1 h. The nylon thread was then withdrawn for reperfusion.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 affect MAP significantly but significantly reduced infarct area, brain water content, NFD and mortality rate and improved focal cerebral blood flow after MCAO. Conclusion Valsartan pretreatment can decrease cerebral infarct area induced by MCAO through improvement of focal cerebral blood flow after MCAO.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
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)
