摘要
目的:通过建立脑缺血再灌注小鼠模型,观察白细胞介素-33(IL-33)阳性细胞在脑缺血再灌注小鼠大脑中的表达和定位情况,初步探讨IL-33在缺血性脑卒中中的作用。方法:采用线栓法制作右侧大脑中动脉阻塞(MCAO)建立脑缺血再灌注小鼠模型,利用TTC染色检测MCAO后脑梗死形成情况,采用免疫荧光组织化学染色法检测IL-33在脑缺血再灌注小鼠大脑中的表达。结果:成功建立脑缺血再灌注小鼠模型,脑缺血再灌注可引起小鼠大脑内IL-33表达升高;脑缺血再灌注小鼠模型脑内广泛表达IL-33。IL-33在神经元、星形胶质细胞、小胶质细胞内均有表达。结论:脑缺血再灌注小鼠脑内IL-33表达增加,IL-33可能参与小鼠缺氧缺血性脑损伤过程。
Objective: To establish cerebral ischemia-reperfusion mouse model and detect interleukin-33( IL-33)expression inbrain. Methods: The cerebral ischemia reperfusion mouse model( MCAO) was established by using the thread embolization method,the cerebral infarction formation after MCAO was detected by TTC staining,and the expression of IL-33 in the brain of cerebral ischemia reperfusion mice was detected by immunofluorescence histochemical staining. Results: The mouse model of cerebral ischemia reperfusion was established successfully. The expression of IL-33 in brain could be increased. Il-33 widely expression in brain of mouse model of cerebral ischemia reperfusion.IL-33 is expressed in neurons,astrocytes,and microglia. Conclusion: The expression of IL-33 increased in brain of cerebral ischemia reperfusion mice and IL-33 may be involved in hypoxic ischemic brain injury in mice.
引文
[1] Malik R,Dichgans M. Challenges and opportunities in stroke genetics[J]. Cardiovasc Res,2018 114(9):1226-1240. DOI:10.1093/cvr/cvy068.
[2]Wong KS,Caplan LR,Kim JS. Stroke Mechanisms[J]. Front Neurol Neurosci,2016; 40:58-71. DOI:10. 1159/000448302
[3]Onda H,Kasuya H,Takakura K,et al. Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage[J]. J Cereb Blood Flow Metab,1999,19(11):1279-1288. DOI:10. 1097/00004647-199911000-00013.
[4]Chen H,Sun Y Lai L,et al. Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice[J]. Neuroscience,2015,308:157-168. DOI:10. 1016/j.neuroscience. 2015. 09. 019.
[5]Chen WY,Chang YJ,Su CH,et al. Upregulation of Interleukin-33in obstructive renal injury[J]. Biochem Biophys Res Commun,2016,473(4):1026-1032. DOI:10. 1016/j. bbrc. 2016. 04.010
[6]Milovanovic M,Volarevic V,Radosavljevic G,et al. IL-33/ST2 axis in inflammation and immunopathology[J]. Immunol Res,2012,52(1-2):89-99. DOI:10. 1007/s12026-012-8283-9.
[7]Luo Y,Zhou Y,Xiao W,et al. Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response[J]. Brain Res,2015,1597:86-94. DOI:10. 1016/j. brainres. 2014. 12. 005.
[8]Yang Y,Liu H,Zhang H,et al. ST2/IL-33-Dependent Microglial Response Limits Acute Ischemic Brain Injury[J]. J Neurosci,2017,37(18):4692-4704. DOI:10. 1523/JNEUROSCI. 3233-16. 2017.
[9] Zhang Q,Gao T,Luo Y,et al. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats:its importance for the risk of Alzheimer’s disease[J]. PLo S One,2012,7(3):33722. DOI:10. 1371/journal. pone. 0033722.
[10]罗艺. IL-33促进Th2应答和抑制Th17应答的效应能够缓解小鼠缺血性脑损伤[M].华中科技大学,2014.
[11]Fanny M,Nascimento M,Baron L,et al. The IL-33 receptor ST2regulates pulmonary inflammation and fibrosis to bleomycin[J].Front Immunol,2018,9:1476. DOI:10. 3389/fimmu. 2018.01476.
[12]Pawel S,Maciej M,Maciej Z,et al. Novel interleukin-33 and its soluble ST2 receptor as potential serum biomarkers in parotid gland tumors[J]. Exp Biol Med(Maywood),2018,243(9):762-769. DOI:10. 1177/1535370218774539.
[13]O’Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily:10 years of progress[J]. Immunol Rev,2008,226:10-18.DOI:10. 1111/j. 1600-065X. 2008. 00701. x
[14]Martin P,Palmer G,Rodriguez E,et al. Atherosclerosis severity is not affected by a deficiency in IL-33/ST2 signaling[J]. Immun Inflamm Dis,2015,3(3):239-246. DOI:10. 1002/iid3. 62.
[15]Yasuoka S,Kawanokuchi J,Parajuli B,et al. Production and functions of IL-33 in the central nervous system[J]. Brain Res,2011,1385:8-17. DOI:10. 1016/j. brainres. 2011. 02. 045.
[16] Gao Y,Luo CL,Li LL,et al. IL-33 provides neuroprotection through suppressing apoptotic,autophagic and NF-κB-mediated inflammatory pathways in a rat model of recurrent neonatal seizure[J]. Mol Neurosci,2017,10:423. DOI:10. 3389/fnmol. 2017.00423.
[17]高雪明,李明才,王亚清,等. IL-33及其在中枢神经系统疾病中的作用[J].中国病理生理杂志,2012,28(10):1901-1905.DOI:10. 3969/j. issn. 1000-4718. 2012. 10. 032.