阿替普酶对急性脑梗死大鼠血管内皮细胞中Claudin-1和Claudin-5蛋白表达的影响

doi:10.13481/j.1671-587x.20170613

Abstract

Abstract: Objective:To investigate the effect of alteplase on the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells after thrombolysis in the rats with acute cerebral infarction and its mechanism, and to provide experimental evidence for its clinical application. Methods:The models of acute thrombosis of middle cerebral artery of the rats were established.Fifty-four SD rats were randomly divided into sham operation group, model group and alteplase group(n=18).The ultrastructure of brain endothelial cells of the rats was observed under transmission electron microscope.The expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats were detected by immunoflurorescence and Western blotting methods. Results:The transmission electron microscope results showed that the brain volume in the ischemic area of the rats in model group was significantly increased and the endothelial cells were swollen, some of the cortical and surrounding brain tissues had obvious boundaries,and the thickness of the basement membrane was uniform and the tightly connected structure was very loose and disappeared; the swelling condition of the capillary endothelial cells in infarcted area of the rats in alteplase group was significantly reduced and the thickness of the basement membrane was improved, and most of the tightly connected structures between the brain capillary endothelial cells and the endothelial cells were loose and the fracture was lost and the structure disappeared. The immunofluorescence results showed that the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in alteplase group were significantly improved compared with model group. The Western blotting results showed the expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in model group were significantly decreased compared with sham operation group(P<0.01);compared with model group,the expression levels of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats in alteplase group at different time points were increased(P<0.01). Conclusion:Alteplase can improve the structure of brain endothelial cells in the rats with acute cerebral infarction, and the mechanism may be related to decreasing the expressions of Claudin-1 and Claudin-5 proteins in the vascular endothelial cells of the rats induced by alteplase.

Key words: alteplase, acute cerebral infarction, vascular endothelial cells, Claudin-1, Claudin-5

CLC Number:

R743.33

ZHU Yunbo, LI Jiajia, MA Zheng, ZHAO Liang. Effect of alteplase on expressions of Claudin-1 and Claudin-5 proteins in vascular endothelial cells of rats with acute cerebral infarction[J].Journal of Jilin University Medicine Edition, 2017, 43(06): 1137-1141.

References

[1] 张秋月.急性脑梗死治疗的研究进展[J]. 数理医药学杂志,2015,28(5):742-744.
[2] 刘静, 吴雅坤, 吕宪民, 等. 急性脑梗死rt-PA溶栓治疗进展[J]. 河北医科大学学报, 2016,37(3):355-357.
[3] Huang X,Cheripelli BK,Lloyd SM, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke(ATTEST):a phase 2, randomised, open-label, blinded endpoint study[J].Lancet Neurol,2015,14(4):368-376.
[4] Rha JH, Shrivastava VP, Wang Y, et al. Thrombolysis for acute ischaemic stroke with alteplase in an Asian population:results of the multicenter, multinational Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW)[J]. Int J Stroke,2014,9(Suppl A100):93-101.
[5] Whiteley WN, Emberson J, Lees KR, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke:a secondary analysis of an individual patient data meta-analysis[J]. Lancet Neurol,2016, 15(9):925-933.
[6] Li M, Wang-Qin RQ, Wang YL, et al. Symptomatic intracerebral hemorrhage after intravenous thrombolysis in Chinese patients:comparison of prediction models[J]. J Stroke Cerebrovasc Dis,2015,24(6):1235-1243.
[7] Chen S,Yang Q,Chen G,et al. An update on inflammation in the acute phase of intracerebralhemorrhage[J]. Transl Stroke Res,2015,6(1):4-8.
[8] Chen Y,Zhu W,Zhang W,et al. A novel mouse model of thromboembolic stroke[J]. J Neurosci Methods, 2015,256:203-211.
[9] 房硕, 胡沛霖, 王建民, 等. 急性后循环脑梗死血管内治疗研究进展[J]. 临床荟萃,2016,31(8):913-918.
[10] 成峰,吴宗艺. 静脉溶栓联合血管内治疗对急性后循环脑梗死临床疗效分析[J].深圳中西医结合杂志,2016,26(3):95-97.
[11] 牛国忠. 急性脑梗死血管内治疗新进展[J]. 浙江省科学技术协会会议论文集,2015,5(1):15-17.
[12] Zobel K, Hansen U, Galla HJ. Blood-brain barrier properties in vitro depend on composition and assembly of endogenous extracellular matrices[J]. Cell Tissue Res,2016,365(2):233-245.
[13] Schossleitner K,Rauscher S,Gröger M, et al. Evidence that cingulin regulates endothelialm barrier function in vitro and in vivo[J]. Arterioscler Thromb Vasc Biol,2016,36(4):647-654.
[14] Chao AC, Lee TC, Juo SH, et al. Hyperglycemia increases the production of amyloid beta-peptide leading to decreased endothelial tight junction[J]. CNS Neurosci Ther,2016,22(4):291-297.
[15] Cai H, Liu W, Xue Y, et al. Roundabout 4 regulates blood-tumor barrier permeability through the modulation of ZO-1, Occludin, and Claudin-5 expression[J]. J Neuropathol Exp Neurol,2015,74(1):25-37.
[16] Peng S, Wang SB, Singh D, et al. Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression[J]. Exp Eye Res,2016,151:179-189.
[17] Ji C, Wang L, Dai R, et al. Hyperthermia exacerbates the effects of cathepsin L on claudin-1 in a blood-brain barrier model in vitro[J]. Brain Res,2016,1631:72-79.
[18] Wang J, Chen J, Tang Z, et al. The effects of copper on brain microvascular endothelial cells and claudin via apoptosis and oxidative stress[J]. Biol Trace Elem Res,2016,174(1):132-141.
[19] Li B, Li Y, Liu K,et al. High glucose decreases claudins-5 and -11 in cardiac microvascular endothelial cells:Antagonistic effects of tongxinluo[J]. Endocr Res,2017,42(1):15-21.
[20] Abadier M, Haghayegh Jahromi N, Cardoso Alves L,et al. Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood-brain barrier[J]. Eur J Immunol,2015,45(4):1043-1058.
[21] 周晓俊, 边莹, 李莉,等. 菖葛益智方对血管性认知功能障碍大鼠脑组织微血管内皮细胞occludin和claudin-5表达的影响[J]. 陕西中医, 2016, 37(11):1550-1552.
[22] 曹解华,刘德荣,刘尚章,等.颈动脉斑块与脑梗死相关性分析[J].中国实用内科杂志,2015,35(1):40-41.
[23] 郑鲲,谭娟,冯辉斌.醒脑静联合依达拉奉治疗急性脑梗死昏迷疗效观察[J].中国实用内科杂志,2015,35(1):46-47.

Effect of alteplase on expressions of Claudin-1 and Claudin-5 proteins in vascular endothelial cells of rats with acute cerebral infarction

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 7

Metrics

Comments

Recommended 0

[1]	GENG Yurong, LIU Yingjie, ZHANG Huili, WANG Hong. Clinical characteristics of patients with hyperthyroidism complicated with acute cerebral infarction and evaluation on prognosis and safety of intravenous thrombolysis treatment [J]. Journal of Jilin University Medicine Edition, 2017, 43(02): 369-374.
[2]	YUAN Zhaoxin, ZHEN Meichun, LIU Yi, CHEN Ran, FAN Xiaofang, GONG Yongsheng, KONG Xiaoxia. Expression of apelin on PVECs injury induced by hypoxia and its significance [J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 747-750.
[3]	XIONG Yingqiong, PAN Jie, WU Xiaomu, CHENG Shaomin. Evaluation on clinical curative effect of myoelectricity triggering biofeedback in treatment of early hemiplegia of cerebral infarction patients [J]. Journal of Jilin University Medicine Edition, 2015, 41(01): 156-159.
[4]	. Influence of Xuebijing in production of NO and  expressions of iNOS and NF-κB induced by LPS in vascular endothelial cells [J]. Journal of Jilin University Medicine Edition, 2014, 40(05): 997-1001.
[5]	LI Yan-bo,ZHOU Wei,YU Yong-bo,DUAN Jun-chao,GUO Cai-xia,SUN Zhi-wei. Cytotoxicity and oxidative damage effect of silica nanoparticles on vascular endothelial cells [J]. Journal of Jilin University Medicine Edition, 2014, 40(03): 476-481.
[6]	LI Bo\|WU Hui-ying\|PIAO Hu-lin\|LIU Ke-xiang. Effects of growth differentiation factor 5 on proliferation and movement of endothelial cells [J]. J4, 2011, 37(6): 1062-1064.
[7]	LU Gang, YUAN Chang-Ji, HAN Wei, MA Hai-Chun, DIAO Heng-Lan. Effect of hypertonic solution on free calcium in human umbilical vein endothelial cells suffering from hypoxia／reoxygenation [J]. J4, 2009, 35(4): 612-615.