不同剂量1,25二羟基维生素D3预处理对大鼠局灶性脑缺血再灌注损伤的保护作用及机制探讨  

Study of effect and the mechanism of different doses of 1,25 dihydroxy vitamin pretreatment on focal cerebral ischemia and reperfusion injury

作　　者：许峰峰[1] 刘信龙[1] 徐正平[1] 杨冰[1] 李明[1] 张建忠[1] 肖丽鸿[1] 廖环[1] 丁强[1] 李政卫 

机构地区：[1]中国人民解放军第455医院,上海200052

出　　处：《临床和实验医学杂志》2015年第4期274-277,共4页Journal of Clinical and Experimental Medicine

基　　金：全军医药卫生科研基金课题

摘　　要：目的探讨不同剂量1,25二羟基维生素D3预处理对大鼠局灶性脑缺血再灌注损伤的保护作用及机制。方法将60只SD雄性大鼠随机分为假手术组、局灶性脑缺血再灌注损伤模型组,并用高、中、低不同剂量1,25二羟基维生素D3对大鼠进行预处理,比较各组氧化/抗氧化指标、微血管密度(MVD)和微血管面积密度(MVA)、血管内皮生长因子(VEGF)和核因子-κB(NF-κB)结果。结果随着剂量增加,各组神经行为学评分和脑梗死面积逐渐降低,高剂量组与中、低剂量组差异具有统计学意义(P<0.05);不同1,25二羟基维生素D3剂量大鼠超氧化物歧化酶(SOD)和过氧化氢酶(CAT)明显升高,脂质过氧化物(LPO)和晚期蛋白质氧化产物(AOPP)明显下降,LPO和CAT三个剂量组间两两比较差异具有统计学意义(P<0.05),高剂量组SOD、AOPP与中、低剂量组差异有统计学意义(P<0.05),但中、低剂量组差异无统计学意义(P>0.05);MVD、MVA和VEGF均有增加趋势,且各组间差异具有统计学意义(P<0.05);随着剂量增加,各组NF-κB均呈现下降趋势,且随着反应时间延长,高剂量组干预效果更为明显(P<0.05),中、低剂量组差异逐渐减少(P>0.05)。结论 1,25二羟基维生素D3对局灶性脑缺血再灌注损伤的保护作用具有剂量依赖性,其机制可能与抑制NF-κB炎性信号通路、减少氧自由基损伤和促进微血管再生有关。Objective To investigate the protective effects and mechanism of different doses of 1,25 dihydroxy vitamin preconditioning on focal cerebral ischemia reperfusion injury.Methods 60 male SD rats were randomly divided into sham operation group,model group.All these rats were pretreated with different doses of VD3.The oxidant / antioxidant index,microvessel density,VEGF and NF-кB activity were compared.Results With the increase of dosage,neurological behavior score and area of cerebral infarction were gradually decreased.There was statistical significance differences in high dose group and medium and low dose group（ P0.05）.SOD and CAT of different doses of VD3 rats were significantly increased.The LPO and AOPP were decreased,LPO and CAT3 were statistically significant differences between groups（ P0.05）.There was statistically significant difference in SOD,AOPP of high dosage group to those in medium and low dose group（ P0.05）,but no significant difference in the low dose group and medium does group（ P0.05）.The increasing trend of MVD,MVA and VEGF were found in this study.The differences between the groups were significant（ P0.05）.With the increase of dosage,NF-кB showed a downward trend in groups with the reaction time.The effect of high dose group was more obvious（ P0.05）.The differences between medium and low dose group were decreased gradually（ P0.05）.Conclusion The protective effect of VD3 on focal cerebral ischemia reperfusion injury was dependent on dose.Its mechanism may be related to inhibition of NF-кB inflammatory signal transduction and reducing the oxygen free radical damage and promote micro angiogenesis.

关 键 词：大鼠 局灶性脑缺血再灌注损伤 1.25二羟基维生素D3 NF-κB 微血管密度 

分 类 号：R743.3[医药卫生—神经病学与精神病学]