7-硝基吲唑在大鼠局灶性脑缺血／再灌注损伤中的双向作用  

The bidirectional role of 7-nitroindazole in focal cerebral ischemiaJreperfusion injury in rats

作　　者：张晨[1] 徐晓梅[1] 王志萍[2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室&江苏省麻醉与镇痛应用技术重点实验室,221002 [2]南京医科大学附属无锡市人民医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2014年第2期106-109,共4页International Journal of Anesthesiology and Resuscitation

摘　　要：目的研究神经元型一氧化氮合酶neuronalnitricoxidesynthase，nNOS）抑制剂7硝基吲唑（7-nitroindazole，7-NI）在局灶性脑缺血，再灌注损伤（ischemia／reperfusioninjury，I／RI）中的双向作用，并初步探讨造成这种现象的原因。方法健康雄性sD大鼠，8周龄一10周龄，体重250g^280g，采用线栓法阻塞右侧大脑中动脉，制备局灶脑缺血／再灌注（ischemia／reperfusion，UR）模型，将造模成功的大鼠用随机数字表法分为4组（每组6只）：假手术组sham组）、脑I／R＋溶剂二甲基亚砜（dimethylsulfoxide，DMSO）组（vehicle组）、脑I／R＋7-N175mg／kg＋溶剂DMSO组（高剂量组）、脑I／R＋7-N125mg／kg＋溶剂DMSO组（低剂量组）。vehicle组、高剂量组和低剂量组分别于栓塞成功后4h腹腔注射10％DMSO或相应剂量的7-NI（溶于DMSO中）。缺血时间为2h。于栓塞成功后2,4、24h进行行为学评分；然后处死大鼠，断头取脑，测定一氧化氮（nitricoxide，NO）含量，nNOS活性和脑梗死体积。结果与sham组比较，vehicle组和高剂量组24h行为学评分明显升高，vehicle组和低剂量组NO含量和nNOS活性明显升高（P〈0．05）。与vehicle组比较，高剂量组的24h行为学评分明显升高，NO含量和nNOS活性明显降低，脑梗死体积明显增加[（18．0±5．8）％vs（24．6±4．7）％]，低剂量组的24h行为学评分明显降低，NO含量和nNOS活性明显降低，脑梗死体积明显减少[（7．4±2．6）％VS（18．0±5．8）％]（P〈0．05）。与高剂量组比较，低剂量组的NO含量和nNOS活性明显升高（P〈0．05）。结论脑I／RI后应用低剂量7-NI有保护作用，而高剂量7-NI则有损害作用，这可能是由于nNOS在损伤细胞中仍然存在着基础的生理作用。Objective To study the bidirectional effects of 7-nitroindazole （7-NI） on focal cerebral ischemia/reperfusion injury （I/RI） in rats, and preliminarily investigate the cause of this phenomenon. Methods Healthy male, 8-10 weeks old, 250 g- 280 g SD rats were used in this study. The rat model with temporary focal cerebral ischemia was established by rat middle cerebral artery occlusion. Animals were randomly divided into 4 groups （n=6）： sham group, cerebral ischemia/reperfusion （I/R）＋dimethyl sulfoxide（DMSO） group（vehicle group）, cerebral I/R＋ 7-NI 75 mg/kg＋DMSO group （high dose group）, cerebral I/R＋ 7-NI 25 mg/kg＋ DMSO group（low dose group）. Four hours after occlusion, the rats of vehicle group were injected intraperitoneally with 10% DMSO, while the high dose group and low dose group were administrated with 75 mg/kg 7-NI and 25 mg/kg 7-NI, respectively. Neurobehavioral scores were evaluated at the time points of 2, 4, 24 h after focal cerebral ischemia. Then rats were sacrificed to detect the level of nitric oxide （NO）, the activity of neuronal nitric oxide synthase （nNOS） and the volumes of cerebral infarction. Results Compared with sham group, neurobehavioral scores after occlusion were significantly increased in vehicle group and high dose group, while the NO level and the activity of nNOS were significantly increased in vehicle and low dose group （P〈0.05）. Compared with vehicle group, neurobehavioral scores after occlusion were increased, while NO level and nNOS activity were significantly reduced, accompanied with increased cerebral infarction volume in the high dose group[ （18.0±5.8）% vs（24.6±4.7）% ]. While in the low dose group, the neurobehavioral scores after occlusion were reduced, with reduced NO level, nNOS activity and cerebral infarction volumes[ （7.4±2.6）% vs （18.0±5.8）% ] （P〈0.05）. When compared with high dose group, the NO level and nNOS activity in low dose group were significantly increased （P〈0.05）. Conclu

关 键 词：脑 再灌注损伤 神经元型一氧化氮合酶 7-硝基吲唑 

分 类 号：R743.31[医药卫生—神经病学与精神病学]