抑制Hippo通路对脑缺血再灌注大鼠海马神经元凋亡的影响  

Effect of inhibiting Hippo pathway on hippocampal neuron apoptosis in rats with cerebral ischemia-reperfusion

作　　者：严兴丽 冶生寿 王新兰 丁小强 YAN Xing-li;YE Sheng-shou;WANG Xin-lan;DING Xiao-qiang(Department of Neurology,Specialist Hospital of Cardiovascular and Cerebrovascular Diseases,Xining 810012,China)

机构地区：[1]青海省心脑血管病专科医院神经内科,青海西宁810012

出　　处：《生物技术》2021年第5期473-477,共5页Biotechnology

基　　金：青海省科学技术项目(9632020Y0524)。

摘　　要：[目的]分析抑制Hippo通路对脑缺血再灌注损伤(ischemia-reperfusion injury,IRI)大鼠模型海马神经元凋亡和学习记忆能力的影响。[方法]36只大鼠随机分为Sham组、IRI组和IRI+XMU-MP-1组(N=12)。IRI组和IRI+XMU-MP-1通过"线栓法"建立IRI模型,IRI+XMU-MP-1组腹腔注射XMU-MP-1(2 mg/kg)干预。干预后通过水迷宫实验和跳台实验分析各组的大鼠的神经功能、学习和记忆能力。并比较海马神经元凋亡、组织中Hippo通路以及自噬的水平。[结果]相比于Sham组,IRI组穿越平台次数降低(3.25±0.58次vs 5.21±0.41次),逃避潜伏期升高(39.02±4.85s vs 27.59±3.41s)(P <0.05),IRI+XMU-MP-1组的逃避潜伏期(33.43±4.76次)低于IRI组并且穿越平台次数(4.16±0.56次)高于IRI组(P <0.05)。IRI组潜伏期明显降低(112.26±12.38s vs145.53±7.12s),错误次数明显升高(3.86±0.57次vs 1.87±0.21次;3.64±0.58次vs145.53±7.12次)(P <0.05),IRI+XMU-MP-1组的错误次数(3.24±0.51次,2.82±0.47次)明显低于IRI组,潜伏期(129.86±11.45s)明显高于IRI组(P <0.05)。IRI组大鼠海马组织中LAST1、YAP蛋白磷酸化水平(1.53±0.15,1.40±0.13)和凋亡率(15.04±1.58%)显著高于Sham组(P <0.05),IRI+XMU-MP-1组p-LAST1/LAST1(0.41±0.05)、p-YAP/YAP(0.98±0.10)和凋亡率(11.04±1.42%)水平显著低于IRI组(P <0.05)。IRI组大鼠海马组织中自噬蛋白Beclin1和LC3蛋白水平(0.76±0.07,0.72±0.07)显著低于Sham组(P <0.05)。IRI+XMU-MP-1组的Beclin1和LC3蛋白水平(2.64±0.25,2.86±0.24)显著高于IRI组(P <0.05)。[结论]在脑IRI大鼠模型中,Hippo通路被激活,而抑制Hippo通路可以通过调控海马体神经元的自噬和抑制凋亡保护IRI大鼠模型的学习和记忆力。[Objective]To analyze the effects of inhibiting Hippo pathway on hippocampal neuron apoptosis and learning and memory in ischemia-reperfusion injury( IRI) rat model.[Method]36 rats were randomly divided into Sham group,IRI group and IRI + XMU-MP-1 group( N = 12). The IRI group and IRI + XMU-MP-1 established the IRI model by the "thread bolt method". In the IRI + XMU-MP-1 group,XMU-MP-1( 2 mg·kg^(-1)) was injected intraperitoneally. After intervention,the neurological function,learning and ability of rats in each group were analyzed by water maze experiment and platform jumping experiment. The levels of hippocampal neuronal apoptosis,tissue Hippo pathway and autophagy were compared. [Result] Compared with the Sham group,the number of platform crossing in the IRI group decreased( 3. 25 ± 0. 58 times vs 5. 21± 0. 41 times) and the escape latency increased( 39. 02 ± 4. 85 s vs 27. 59 ± 3. 41 s)( P < 0. 05). The escape latency in the IRI + XMU-MP-1 group( 33. 43 ± 4. 76 s) was lower than that in the IRI group and the number of platform crossing( 4. 16± 0. 56 times) was higher than that in the IRI group( P < 0. 05). The incubation period of the IRI group was significantly decreased( 112. 26 ± 12. 38 s vs 145. 53 ± 7. 12 s),and the number of errors was significantly increased( 3. 86 ± 0. 57 times vs.1. 87 ± 0. 21 times;3. 64 ± 0. 58 times vs 145. 53 ± 7. 12 times)( P < 0. 05). The number of errors in the IRI + XMU-MP-1 group( 3. 24 ± 0. 51 times,2. 82 ± 0. 47 times) were significantly lower than that in the IRI group,and the incubation period( 129. 86 ± 11. 45 s) was significantly higher than that in the IRI group( P < 0. 05). The phosphorylation level of LAST1 and YAP protein( 1. 53 ± 0. 15,1. 40 ± 0. 13),and apoptosis rate( 15. 04 ± 1. 58%) in hippocampus tissue of IRI group were significantly higher than that of Sham group( P < 0. 05). The levels of p-LAST1/LAST1( 0. 41 ± 0. 05),p-YAP/YAP( 0. 98± 0. 10) and apoptosis rate( 11. 04 ± 1. 42%) in the IRI + XMU-MP-1 group were significantly lower tha

关 键 词：脑缺血 缺血再灌损伤 海马体 Hippo通路 凋亡 自噬 

分 类 号：R743.9[医药卫生—神经病学与精神病学]