白藜芦醇对慢性脑低灌注大鼠认知功能损害的保护作用

Protective effect of resveratrol on chronic cerebral hypoperfusion-induced cognitive impairment in rats

目的观察白藜芦醇对慢性脑低灌注大鼠认知功能损害的影响，并探讨白藜芦醇抗氧化机制在其中的作用。方法采用永久性双侧颈总动脉结扎术（2VO）制备慢性脑低灌注大鼠模型，健康雄性Wistar大鼠随机分为假手术组、2VO组、2V0＋白藜芦醇组。通过Morris水迷宫观察大鼠的空间学习及记忆功能，免疫组化检测皮质及海马CA1区4-羟基壬烯醛（4-hydroxynonenal，4-HNE）和8-羟化脱氧鸟苷（8-hydroxy-2′-deoxyguanosine，8-OHdG）表达的变化，以反应脂质和DNA的氧化性损伤。结果2VO组大鼠第3～5天逃逸潜伏期分别为（42．1±5．4）s、（36．4±4．4）S、（30．4±4．O）S，与假手术组大鼠（25．1±3．3）s、（12．4±3．3）s、（8．1±3．4）s相比，逃逸潜伏期明显延长（q=10．91、14．54、14．07，均P〈0．01），2VO组大鼠目标象限探索时间（12．9±2．5）S，明显少于假手术组（18．9±2．2）s（q=6．47，P〈0．01）；2VO＋白藜芦醇组大鼠第3～5天逃逸潜伏期分别为（29．5±4．0）s、（25．6±4．3）s、（19．8±4．2）S，与2VO组大鼠（42．1±5．4）s、（36．4±4．4）S、（30．4±4．0）S比较，逃逸潜伏期缩短（q=7．71、6．22、6．37，均P〈0．01），2VO＋白藜芦醇组大鼠目标象限探索时间（16．5±1．8）S，比2VO组大鼠（12．9±2．5）S延长（q=3．83，P〈0．05）。2VO组大鼠皮质与海马CA1区的8-OHdG平均积分光密度值（IOD）分别为265．1±9．0和37．8±5．0，与假手术组168．2±6．0和24．0±4．0相比均增加（q=31．89、7．48，均P〈0．01）；2VO＋白藜芦醇组与2VO组相比，皮质与海马CA1区的8-OHdG平均IOD均降低，分别为195．1±7．0和26．0±4．3（q=23．03、6．49，均P〈0．01）。结论白藜芦醇能减轻大鼠慢性脑低灌注所致的血管性认知功能损害，其作用可能与抑制慢性脑低灌注后的氧化性损伤有关。

Objective To observe the effect of resveratrol on cognitive impairment in rats after chronic cerebral hypoperfusion, and to explore the underlying antioxidant mechanism of resveratrol. Methods The chronic cerebral hypoperfusion model was induced by permanent occlusion of bilateral common carotid arteries （2VO） in rats. Healthy male Wistar rats were randomly divided into 3 groups： sham-operated group, 2VO group and 2VO＋resveratrol group. Spatial learning and memory were assessed using the Morris water maze at 4 weeks after the occlusion. The levels of 4- Hydroxynonenal （ 4-HNE ） and 8-Hydroxy-2＇-deoxyguanosine （ 8-OHdG ） in the cortex and hippocampal CA1 areas were detected using immunohistochemistry staining, for reflecting the lipid peroxidation and oxidative DNA damage. Results The escape latencies from the third day to the fifth day were longer in 2VO group than in sham-operated group [（42.1±5.4）s vs. （25.1±3.3）s, （36.4±4.4）svs. （12.4±3.3） s, （30.4±4.0）s vs. （8.1±3.4）s,q=10.91,14.54 and 14.07, all P 〈0. 013, while the time spent in the object square was shorter in 2VO group than in sham-operated group [（12.9±2.5）s vs. （18.9±2.2）s, q=6.47, P〈0.01]. Compared with 2VO group, the escape latencies in 2VO＋resveratrol group from the third day to the fifth day were shorter [（29.5 ±4.0）s, （25.6±4.3）s and （19.8±4.2）s, q=7.71, 6.22 and 6.37, all P〈0.01], while the time spent in the object square was longer [（16.5±1.8）s, q=3.83, P〈0.05]. Compared with the sham operated group, the mean integral optical density （IOD） of 4 HNE and 8-OHdG in the cortex and hippocampus CA1 area were increased in 2VO group （265.1 ± 9.0 vs. 168.2 ±6.0, 37.8 ±5.0 vs. 24.0±4.0, q=31.89 and 7.48, both P〈0.01）. And in the 2VO-t-resveratrol group, the mean IOD of 4-HNE and 8-OHdG in the cortex and 8-OHdG in hippocampus CA1 area were lower than in 2VO group （195.1±7.0, 26.0±4.3, q=23.03 and 6.49, both P〈0.01）. Conclusions Resveratrol can improve the cognitive impairment in rats after chronic cerebral hypoperfusion, which may be related to preventing oxidative damage.