BQ-123对蛛网膜下腔出血大鼠神经功能缺陷的改善作用及其机制

doi:10.13481/j.1671-587x.20160517

Abstract

Abstract:

Objective: To study the effect of endothelin receptor antagonist BQ-123 on the nerve function damage after subarachnoid hemorrhage (SAH) in the rats, and to explore the mechanisms. Methods: Total 120 male SD rats were divided into sham group, SAH group, low dose of BQ-123 group (50 μg·kg^-1) and high dose of BQ-123 group(75 μg·kg^-1). The SAH rat models were established by injecting the autologous blood into cisterna magna twice. The morphological changes of hippocampus nerve cells of rat brain tissue were detected with HE staining, and the expressions of mTOR, Beclin-1 and LC3-Ⅱ in the hippocampus of rats were detected with immunohistochemistry and RT-PCR; the shuttle-box experiment was used to evaluate the abilities of learning and memory, and the holding power evaluation was used to evaluate the forelimb pulling force of the rats in various groups at each time point. Results: Compared with sham group, the morphological damages of neurons of the rats in SAH group were increased, the survival rate of neurons of the rats in SAH group was decreased(P<0.05), the expression levels of mTOR mRNA, Beclin-1 mRNA and LC3-Ⅱ mRNA in hippocampus tissue of the rats were increased(P<0.05), and the abtilities of learning and memory and the values of holding power were decreased(P<0.05). Compared with SAH group, the morphological damages of neurons of the rats in BQ-123 groups were decreased, the survival rates of neurons of the rats in BQ-123 groups were increased(P<0.05), the expression levels of mTOR mRNA of rats were decreased(P<0.05), the expression levels of Beclin-1 mRNA and LC3-Ⅱ mRNA in hippocampus tissue were increased(P<0.05), and the abilities of learning and memory and the values of holding power were increased(P<0.05).The changes were more significant in high dose of BQ-123 group compared with low dose of BQ-123 group(P<0.05). Conclusion: BQ-123 can improve the nerve function damage after SAH in the rats, its mechanism may be related to regulating the mTOR/autophagy signaling pathway.

Key words: subarachnoid hemorrhage, mammalian target of rapamycin, autophagy related gene, beclin-1, microtubule-associated proteins

CLC Number:

R651.1

ZHAO Yaning, ZHAO Xu, GUO Xiangfei, LI Jianmin, XUE Chengjing. Improvement effect of BQ-123 on nerve function damage after subarachnoid hemorrhage in rats[J].Journal of Jilin University Medicine Edition, 2016, 42(05): 925-931.

References

[1] Le Roux AA, Wallace MC, Wallace. Outcome and cost of aneurysmal subarachnoid hemorrhage[J]. Neurosurg Clin N Am, 2010, 21(2):235-246.

[2] 王俊华. 蛛网膜下腔出血40例临床治疗效果分析[J]. 西南军医, 2012, 14(1):46-48.

[3] 幸志强, 丁春平, 邱志宏, 等. ETA受体拮抗剂BQ123对心肌梗死局部心肌组织中ET-1和ET受体分布的影响[J]. 中华老年多器官疾病杂志, 2005, 4(3):204-207.

[4] D'SouzaS. Aneurysmal subarachnoid hemorrhage[J]. J Neurosurg Anesthesiol, 2015,27(3):222-240.

[5] Topkoru BC, Altay O, Duris K, et al. Nasal administration of recombinant osteopontin attenuates early brain injury after subarachnoid hemorrhage[J]. Stroke, 2013, 44(11):3189-3194.

[6] 汪文英,崔德荣,江伟.自噬在大脑缺血再灌注损伤中作用的研究进展[J]. 上海交通大学学报:医学版, 2014, 34(2):248-253.

[7] Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress[J]. Mol Cell, 2010, 40(2):310-322.

[8] 马朝晖, 李贵福, 罗望池, 等. 改良"二次枕大池注血法"构建Wistar大鼠蛛网膜下腔出血模型[J]. 中国神经精神疾病杂志, 2012, 38(3):190-192.

[9] 肖遥, 徐善才, 史怀璋. 自噬在蛛网膜下腔出血后早期脑损伤中作用的研究进展[J]. 中国脑血管病杂志, 2013,10(10):553-556.

[10] 杨鹏,赵冬,刘祺,等.氨基胍在大鼠蛛网膜下腔出血后早期脑损伤中的作用[J].医学研究生学报,2015,28(8):794-798.

[11] 姜永生, 叶启发, 陈卫民, 等. BQ123与L-arginine在肝脏缺血再灌注损伤中的作用研究[J]. 肝胆外科杂志, 2001, 9(6):472-473.

[12] Josko J. Cerebral angiogenesis and expression of VEGF after subarachnoid hemorrhage (SAH) in rats[J]. Brain Res, 2003, 981(1/2):58-69.

[13] Itoh S, Sasaki T, Asai A, et al. Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123:change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model[J]. J Neurosurg, 1994, 81(5):759-764.

[14] Ropolo A, Bagnes CI, Molejon MI, et al. Chemotherapy and autophagy-mediated cell death in pancreatic cancer cells[J]. Pancreatology, 2012, 12(1):1-7.

[15] Zhao H, Ji Z, Tang D, et al. Role of autophagy in early brain injury after subarachnoid hemorrhage in rats[J]. Mol Biol Rep, 2013, 40(2):819-827.

[16] 李建柯,刘一之,陈罡,等.Cystatin C对大鼠蛛网膜下腔出血后的自噬的影响[J]. 现代生物医学进展,2013,13(15):2829-2832,2939.

[17] 赵明明, 赵永博, 罗鹏, 等. PI3K/Akt信号通路对神经元机械性损伤诱导的自噬调节作用[J]. 中华神经外科疾病研究杂志, 2012, 11(6):491-494.

[18] Liu L, Fujimoto M, Kawakita F, et al. Anti-vascular endothelial growth factor treatment suppresses early brain injury after subarachnoid hemorrhage in mice[J]. Mol Neurobiol, 2015, 14(4):365.

[19] 庄宗, 赵旭东, 吴颐, 等. PI3K-AKT信号通路在蛛网膜下腔出血后的抗凋亡作用[J]. 医学研究生学报, 2010, 23(6):579-582.

[20] 徐祥. mTOR信号通路在蛛网膜下腔出血后早期脑损伤中的作用及机制研究[D]. 苏州:苏州大学,2014.

[21] 刘琨,许鹏程. 七氟醚预处理对大鼠离体心脏缺血再灌注损伤时自噬的影响及PI3K/Akt信号通路在其中的作用[J]. 中华麻醉学杂志, 2014, 34(4):492-496.

[22] 宫利, 王志, 邢诒刚, 等. 缺血后处理对大鼠脑缺血-再灌注中细胞凋亡的作用及其机制研究[J]. 国际神经病学神经外科学杂志, 2012, 39(3):229-234.

[23] Luo DH, Chen QY, Liu H, et al. The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways[J]. J Transl Med, 2013, 11:203.doi:10.1186/1479-5876-11-203.

Improvement effect of BQ-123 on nerve function damage after subarachnoid hemorrhage in rats

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 6

Metrics

Comments

Recommended 0

[1]	YANG Wanxia, SU Qiang, XING Aihua, ZHANG Xiaoyan. Effects of starvation on autophagy and apoptosis of Beclin-1-dependent Ana-1 cells [J]. Journal of Jilin University Medicine Edition, 2018, 44(04): 704-708.
[2]	DING Xianfei, ZHOU Xueliang, DOU Mengmeng, LI Lifeng, GUO Lina, WANG Feng, FAN Qingxia. Expression of mTOR and its relationship with prognosis of breast cancer: a Meta-analysis [J]. Journal of Jilin University Medicine Edition, 2016, 42(04): 783-788.
[3]	FANG Fang, FANG Qing, ZHAO Liang-zhong, LI Qiang, CHEN Shuang, ZHANG Duo, WANG Liguo. Iihibition of autophagy of prostate cancer PC-3 cells by CD147 with Beclin-1 [J]. Journal of Jilin University Medicine Edition, 2016, 42(01): 15-18.
[4]	HE Jing, QI Di, WANG Daoxin. Mechanism of insulin in up-regulating epithelial sodium channel α-subunit via mTORC2/SGK1 signaling pathway [J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 716-720.
[5]	WU Bing\|KANG Jin-song\| WANG He-yuan,XI Xin,QIU Hai-yang\|WANG Wei-wei. Establishment of rat subarachroid hemorrhage model by second injection of blood into cisterna and protective effect of nimodipine on brain [J]. J4, 2011, 37(6): 1153-1156.
[6]	LIU Yu-he，YU Chun-yan,WANG Hao,SUN Lian-kun. Effect of Vk3 on gene expression of mTOR signaling pathway in cervical carcinoma Hela cells [J]. J4, 2009, 35(2): 267-270.