Apelin-13对血管性痴呆大鼠海马区氧自由基及自噬的影响

Effects of Apelin-13 on oxygen free radicals and autophagy in vascular dementia rats

目的观察Apelin-13对血管性痴呆(VD)大鼠海马区氧自由基及自噬的作用,进一步探讨其对VD大鼠学习记忆功能的影响。方法取健康的雄性SD大鼠,随机分为假手术组、模型组和50μg/kg Apelin-13组和100μg/kg Apelin-13组。利用四血管阻断法建立血管性痴呆模型,给药组侧脑室注射135μL Apelin-13(剂量分别为50和100μg/kg)。造模24 h后取脑,用干湿重法测定大鼠脑含水量;WST-1法测定超氧化物歧化酶(SOD)的活力;TBA法检测丙二醛(MDA)含量;Morris水迷宫测定大鼠的学习记忆功能;Western blot法检测海马区Beclin-1、LC3蛋白水平。结果与模型组相比,50和100μg/kg Apelin-13的定位航行潜伏期缩短(P<0.05或P<0.01),空间探索实验的第1次穿台时间缩短(P<0.05或P<0.01),穿台次数增多(P<0.01)。50和100μg/kg Apelin-13组大鼠脑含水量降低(P<0.05),MDA含量降低(P<0.05或P<0.01),并具有剂量依赖性,SOD活力升高(P<0.05)。50和100μg/kg Apelin-13组Beclin-1蛋白表达降低(P<0.05或P<0.01),具有剂量依赖性;100μg/kg Apelin-13组LC3-Ⅱ/LC3-Ⅰ降低。结论 Apelin-13能够改善VD大鼠学习记忆功能,其机制可能与减少脑含水量,抗自由基损伤和抑制某些自噬蛋白有关。

Objective To explore the effects of Apelin-13 on learning and memory function and brain water content,superoxide dismutase(SOD)and malondialdehyde(MDA)content in vascular dementia(VD)rats.Methods Healthy male Sprague-Dawley rats were randomly divided into sham-operated group,model group,and Apelin-13 group(50 and 100μg/kg,respectively).Vascular dementia model was established by four-vessel occlusion method,and dementia model was established after intracerebroventricular injection of Apelin-13 in the administration group.After 24 hours of modeling,brain water content was measured by wet/dry weight method.The activity of SOD was measured by WST-1 method and the content of MDA by TBA method.After 2 weeks of modeling,the learning and memory function were measured by water maze and the pression of Beclin-1,LC3 were measured by Western blot.Results Compared with the sham-operated group,the rats in model group had shorter latency,more errors,higher brain water content,higher MDA content,lower SOD activity and higher Beclin-1,LC3-Ⅱ/LC3-Ⅰ(P<0.05 or P<0.01).Compared with the model group,in Apelin-13 group,latency was prolonged,errors was fewer,brain water content and MDA content were decreased,SOD activity was increased,the pression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰwere lower(P<0.05 or P<0.01).Conclusion Apelin-13 can improve the learning and memory function in VD rats.The mechanism may be related to the decrease of brain water content,anti-free radical injury which can decrease the pression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ.