西格列汀对局灶性脑缺血再灌注小鼠血-脑脊液屏障通透性的影响及抗凋亡作用  

Effects of sitagliptin on permeability of blood-cerebrospinal fluid barrier and apoptosis after focal cerebral ischemia-reperfusion in mice

作　　者：康宁 解燕昭 石源源 虞武 杨梅柳 Kang Ning;Xie Yanzhao;Shi Yuanyuan;Yu Wu;Yang Meiliu(Department of Neurology,People's Hospital of Hebei Province,Shijiazhuang 050000,China)

机构地区：[1]河北省人民医院神经内科,石家庄050000 [2]衡水学院门诊部 [3]衡水学院生命科学学院

出　　处：《脑与神经疾病杂志》2024年第11期661-666,共6页Journal of Brain and Nervous Diseases

基　　金：河北省医学科学研究课题计划(20190262);衡水学院高层次人才科研启动基金项目(2023GC019)。

摘　　要：目的研究西格列汀(SIT)在非糖尿病的小鼠脑缺血再灌注(I/R)时的神经保护作用。方法采用大脑中动脉栓塞(MCAO)模型,脑缺血60 min后实施再灌注。SIT按低剂量(40 mg·kg^(-1))、高剂量(80 mg·kg^(-1))在手术前口服给药3d,术后再次给药。术后24 h检测小鼠神经功能、梗死体积和脑水肿,通过Western blot评估Bcl-2和Akt的蛋白表达,RT-qPCR评估Bax和Bcl-2的转录水平。SIT对血-脑脊液屏障(BCFB)通透性的影响通过伊文思蓝渗出和Claudin-5的蛋白表达来测量。结果本研究结果表明,SIT可减轻CD-1小鼠大脑中动脉栓塞再灌注24h后的肢体功能障碍,减少脑梗死体积,减轻脑水肿。SIT显著增加Bcl-2和磷酸化Akt的蛋白表达水平,下调Bax、上调Bcl-2的基因表达。减少小鼠脑组织伊文思蓝渗出并增加Claudin-5的蛋白表达水平(^(均)P<0.05)。结论SIT在非糖尿病小鼠的脑I/R急性期,降低神经功能缺损评分、减少脑梗死体积、保护BCFB,具有脑保护作用,机制可能与抗凋亡有关。这些发现为急性缺血性脑血管病的治疗提供新的策略。Objective The objective of this study was to investigate whether sitagliptin(SIT)show neuroprotective effects in a mouse model of cerebral ischemia-reperfusion(I/R)injury.Methods A mouse model of middle cerebral artery occlusion(MCAO)with modification was applied to induce cerebral I/R.Mice were treated with SIT at low(40 mg·kg^(-1))or high(80 mg·kg^(-1))doses for 3 days before surgery and again postoperatively.Neurological function,infarct volume,and edema were assessed 24 hours postoperatively.The protein expression of Akt and Bcl-2 was evaluated by Western blot,and the mRNA expression of Bax and Bcl-2 was evaluated by RTqPCR.The permeability of the blood-cerebrospinal fluid barrier(BCFB)was assessed by measuring the leakage of Evans blue(EB)and the protein expression of Claudin-5.Results The results of this study showed that SIT significantly reduced limb dysfunction 24 hours after I/R,reduced infarct volume,and reduced edema.It also significantly increased the protein expression of Bcl-2 and phosphorylated Akt,downregulated Bax and upregulated Bcl-2 at the gene level.It reduced EB content in brain tissue and increased the protein expression of Claudin-5(^(all)P<0.05).Conclusion In non-diabetic mice with acute cerebral I/R,SIT reduces neurological deficit score,reduces infarct volume,and protects BCFB,demonstrating neuroprotective effects.The mechanism may be related to anti-apoptotic pathway.These findings may provide a possible new strategy for the treatment of acute ischemic cerebrovascular(AIC)disease.

关 键 词：急性局灶性脑缺血再灌注损伤 西格列汀 抗凋亡通路 血-脑脊液屏障 

分 类 号：R744[医药卫生—神经病学与精神病学]