丁苯酞对局灶性脑梗死大鼠氧化应激及内皮型一氧化氮合酶脱耦联的影响

Effect of butylphthalide on oxidative stress and endothelial nitric oxide synthase decoupling of rats with focal cerebral ischemia

目的观察丙二醛（MDA）和内皮型一氧化氮合酶（eNOS）在局灶性脑梗死大鼠的动态表达及丁苯酞干预效应。方法将54只雄性SD大鼠随机分为假手术组、模型组、治疗组。每组再分为3个亚组：1d组、3d组和7d组，每亚组6只。模型组和治疗组采用线栓法制作大鼠大脑中动脉闭塞模型（MCAO），假手术组只分离不结扎。治疗组在大鼠苏醒后以丁苯酞植物油灌胃，假手术组和模型组同法给予等量植物油灌胃。应用硫代巴比妥酸（TBA）法检测脑组织MDA含量，Westernblot检测脑组织eNOS表达，并对两者进行相关分析。结果MDA含量随时间延长从12．005±0．608（模型组）逐渐降至7．315±0．404（模型组）。各时间点模型组12．005±0．608（1d）较治疗组9．323±0．727（1d）增高；治疗组9．323±0．727（1d）较假手术组4．043±0．274（1d）增高。差异均有统计学意义（P〈0．05）。eNOS含量随时问延长从0．136±0．009（模型组）逐渐增加至0．2414-0．012（模型组）；各时间点模型组0．136±0．009（1d）较假手术组0．101±0．012（1d）增高，治疗组0．199±0．010（1d）较模型组0．136±0．009（1d）增高，差异均有统计学意义（P〈0．05）。且MDA含量和eNOS表达呈负相关（P〈0．05）。结论丁苯酞通过减少脑缺血大鼠氧化应激损伤及eNOS脱耦联，发挥神经保护作用，且MDA和eNOS呈负相关。

Objective To investigate the expression of malondialdehyde （MDA） and endothelial nitric oxide synthase （eNOS） in rats with focal cerebral ischemia （FCI） and the effects of butylphthalide （NBP） conditioning. Methods Male SD rats （ n = 54 ） were randomly divided into three groups ： sham, model and NBP - treated groups, and each group was divided into three subgroups： 1 st day group, 3rd day group and 7th day group （n =6 each）. The rat middle cerebral artery occlusion （MCAO） model was es- tablished in model and NBP - treated groups by intraluminal suture technique, and sham group was just given separation of the blood vessels. NBP - Treated group was given NBP vegetable oil by intragastric ad- ministration after recovery from anaesthesia, and sham and model groups given the same dose of vegetable oil. TBA method was used to measure MDA content, and Western blotting to detect the level of eNOS in brain tissue. Correlation analysis was carried on the MDA content and level of eNOS. Results With the extension MDA content was gradually decreased from 12. 005± 0. 608 to 7. 315 ± 0. 404 in model group. The MDA content in model group at 1st day （12. 005±0. 608） was higher than in NBP -treated group at 1 st day （9. 323± 0. 727）, and that in NBP - treated group at 1 st day was higher than in sham group at l st day （4. 043±0. 274）. The differences were all statistically significant （P 〈 0. 05）. With the extension eNOS was gradually increased from 0. 136 ±0. 009 to 0. 241 ±0. 012 in model group, eNOS in model group at 1st day （0. 136 ±0.009） was higher than in sham group at 1st day （0. 101 ±0.012）, and the in NBP-treated group at 1st day （0. 199 ±0. 010） was higher than in model group at 1st day. The differ- ences were all statistically significant （ P 〈 0. 05 ）. The MDA content and eNOS level had a negative corre- lation. Conclusion NBP may play a neuroprotective effect by ameliorating oxidative stress injury and eNOS decoupling on cerebral ischemia rats. MDA content and eNOS level show a negative correlation.