普罗布考对脑出血模型小鼠血肿周围脑组织MST1和LATS1及YAP蛋白表达的影响  

Effects of probucol on the expression of MST1,LATS1 and YAP protein in brain tissue around hematoma in the model mice with intracerebral hemorrhage

作　　者：董晓柳[1] 刘蔚然 高铭 司味鑫 张秀清[1] 宋丽华[1] 张利[2] 董伟[2] DONG Xiaoliu;LIU Weiran;GAO Ming;SI Weixin;ZHAGN Xiuqing;SONG Lihua;ZHAGN Li;DONG Wei(Department of Neurorehabilitation,Tangshan People′s Hospital,Tangshan,Hebei 063000,China;Department of Neurosurgery,Tangshan People′s Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]河北省唐山市人民医院神经康复科,063000 [2]河北省唐山市人民医院神经外科,063000

出　　处：《重庆医学》2022年第7期1100-1105,共6页Chongqing medicine

基　　金：唐山市人才资助项目(CA202010019);河北省医学科学研究课题计划项目(20211512)。

摘　　要：目的观察普罗布考对脑出血(ICH)小鼠血肿周围脑组织哺乳动物不育系20样激酶(MST1)、大肿瘤抑制因子1(LATS1)及Yes相关蛋白-1(YAP)表达的影响,探寻普罗布考发挥脑保护作用的可能机制。方法将54只雄性C57BL/6J小鼠按随机数字表法分为假手术组(sham组)、ICH模型组(ICH组)、ICH模型+普罗布考治疗组(ICH+PB组),每组18只。采用胶原酶法制作ICH模型。ICH+PB组于造模后6 h开始灌胃给药普罗布考(500 mg·kg^(-1)·d^(-1)),sham组和ICH组于相应时间点给予等体积的生理盐水。在ICH后1、3 d采用神经功能损伤(mNSS)评分对小鼠进行神经功能学评价;在ICH后第3天,采用伊文思蓝(EB)渗透法检测小鼠脑组织EB含量;采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测血肿周围脑组织神经元细胞凋亡情况;采用蛋白免疫印迹(Western blot)法检测血肿周围脑组织MST1、LATS1和YAP的表达水平。结果与sham组比较,ICH组小鼠脑组织含水量、EB含量、血肿周围脑组织中神经元细胞凋亡数、磷酸化MST1(p-MST1)和p-LATS1及p-YAP表达水平明显升高,mNSS评分也明显增加(P<0.05)。与ICH组比较,ICH+PB组小鼠脑组织含水量、EB含量、血肿周围脑组织中神经元细胞凋亡数及p-MST1、p-LATS1和p-YAP表达水平明显下降,mNSS评分也明显降低(P<0.05)。结论普罗布考可通过下调p-MST1、p-LATS1及p-YAP表达,发挥对ICH模型小鼠的脑保护作用。Objective To observe the effect of probucol on the expression of mammalian sterile 20-like kinase 1(MST1),large tumor suppressor 1(LATS1)and Yes associated protein(YAP)in the brain tissue around hematoma of the intracerebral hemorrhage(ICH)mice,and to explore the possible mechanism of probucol′s brain protection.Methods A total of 54 male C57BL/6J mice were randomly divided into the sham operation group(the sham group),the ICH model group(the ICH group)and the ICH model+probucol treatment group(the ICH+PB group)by random number table method,with 18 mice in each group.Collagenase method was used to make the ICH model.The ICH+PB group was given probbucol intragastric administration(500 mg·kg^(-1)·d^(-1))at six hours after modeling,while the sham group and ICH group were given equal volume of normal saline at the corresponding time points.MNSS scores were used to evaluate the neurological function of the mice on the 1st and 3rd day after the ICH.On the 3rd day after the ICH.the Evans Blue(EB)leakage method was used to detect the content of EB in the brain tissue of the mice.Deoxyribonucleotide terminal transferase-mediated nick end labeling(TUNEL)method was used to detect the cell apoptosis in the brain tissue around the hematoma.Western-blot method was used to detect the expression levels of MST1,LATS1 and YAP in the brain tissue around the hematoma.Results Compared with those of the sham group,the water content,EB content,apoptosis number in the brain tissue around hematorna,mNSS score,p-MST1,p-LATS1 and p-YAP protein expression levels in the ICH group significantly increased(P<0.05).Compared with those of the ICH group,the water content,EB content,apoptosis number in the brain tissue around hematorna,mNSS score,p-MST1,p-LATS1 and p-YAP protein expression levels in the ICH+PB group decreased significantly(P<0.05).Conclusion Probucol can protect the brain of the ICH model mice by down-regulating the expression levels of p-MST1,p-LATS1 and p-YAP.

关 键 词：脑出血 普罗布考 哺乳动物不育系20样激酶 大肿瘤抑制因子1 Yes相关蛋白-1 

分 类 号：R743.34[医药卫生—神经病学与精神病学]