|本期目录/Table of Contents|

[1]锁志刚,丁惠强,费 乐,等.Caspase-1 抑制剂在大鼠脊髓损伤后的靶点作用[J].宁夏医科大学学报,2021,(02):119-123.[doi:10.16050/j.cnki.issn1674-6309.2021.02.003]
 SUO Zhigang,DING Huiqiang,FEI Le,et al.Targeting of Caspase-1 Inhibitors after Spinal Cord Injury in Rats[J].Ningxia Medical University,2021,(02):119-123.[doi:10.16050/j.cnki.issn1674-6309.2021.02.003]
点击复制

Caspase-1 抑制剂在大鼠脊髓损伤后的靶点作用(PDF)
分享到:

《宁夏医科大学学报》[ISSN:1005-8486/CN:64-1029/R]

卷:
期数:
2021年02期
页码:
119-123
栏目:
基础医学
出版日期:
2021-02-28

文章信息/Info

Title:
Targeting of Caspase-1 Inhibitors after Spinal Cord Injury in Rats
文章编号:
1674-6309(2021)02-0119-05
作者:
锁志刚 丁惠强 费 乐 黑 龙 戈朝晖 马宗军 陈霄雷
(宁夏医科大学总医院脊柱骨科,银川 750004)
Author(s):
SUO Zhigang DING Huiqiang FEI Le HEI Long GE ZhaohuiMA Zongjun CHEN Xiaolei
(Department of Spinal Orthopedics,the General Hospital of Ningxia Medical University,Yinchuan 750004,China)
关键词:
脊髓损伤半胱氨酸天冬氨酸酶-1抑制剂白细胞介素-1β白细胞介素-18大鼠
Keywords:
spinal cord injurycysteine aspartate -1 inhibitorinterleukin-1βinterleukin-18rat
分类号:
R744
DOI:
10.16050/j.cnki.issn1674-6309.2021.02.003
文献标志码:
A
摘要:
目的 目的探讨天冬氨酸特异性半胱氨酸蛋白酶-1(Caspase-1)抑制剂AC.YVAD.CMK在大鼠脊髓损伤(spinal cord injury,SCI)后的靶点作用。方法 将成年雄性Sprague-Dawley(SD)大鼠72只随机分为对照组、SCI组、AC.YVAD.CMK组、甲基强的松龙(methyl prednisolone,MP)组,每组18只。4组大鼠依据损伤后取材时间各分3个亚组。对照组只做全椎板切除,SCI组应用改良的Allen’s重物打击法建立大鼠脊髓损伤模型。分别于术后24 h、72 h、7 d处死各组大鼠,HE染色观察脊髓组织的病理变化,免疫组化染色检测Caspase-1、白细胞介素(IL)-1β及IL-18的表达情况。结果 对照组大鼠脊髓组织中Caspase-1、IL-1β及IL-18阳性细胞有少量表达。术后24 h、72 h、7 d时,SCI组Caspase-1、IL-1β及IL-18阳性表达率均高于对照组(P均<0.01)。24、72 h时,AC.YVAD.CMK组、MP治疗组IL-1β及IL-18阳性表达率均低于SCI组(P均<0.01);AC.YVAD.CMK组Caspase-1、IL-18阳性表达率均较MP组降低,IL-1β阳性表达MP组升高(P均<0.01)。结论 Caspase-1抑制剂可降低脊髓损伤后Caspase-1、IL-1β及IL-18的表达,对SCI后的继发性损伤有一定的靶向抑制作用,可能对脊髓损伤后起到一定的修复作用。
Abstract:
Objective To investigate the effect of Caspase-1 inhibitor AC.YVAD.CMK on spinal cord injury(SCI)in rats. Methods A total of 72 adult male Sprague-Dawley(SD)rats were randomly divided into normal control group,injury control group,AC.YVAD.CMK group,and methyl prednisolone(MP)treatment group,with 18 rats in each group.The four groups were divided into 3 subgroups according to the sampling time after injury.In the control group,only total laminectomy was performed,while in the spinal cord injury group,the modified Allen’s heavy blow method was used to establish the rat spinal cord injury model.The rats of each group were sacrificed at 24 h,72 h and 7 d after the operation,and the pathological changes of spinal cord tissues were observed by using the model center and hematoxylin & eosin(HE)staining.The expression of Caspase-1,IL-1β and IL-18 were detected by immunohistochemical staining. Results There was a small amount of Caspase-1,IL-1β and IL-18 positive cells in the spinal cord tissue of the normal control group,while the expression of Caspase-1,IL-1β and IL-18 positive cells in the spinal cord injury group was high from that in the control group(P all<0.01). There were low positive cells in IL-1β and IL-18 expression in AC.YVAD.CMK group and MP treatment group at 24 h and 72 h postoperatively compared with the spinal cord group(P all<0.01). There were low positive cells in Caspase-1 and IL-18 expression in AC.YVAD.CMK group at 24 h and 72 h postoperatively compared with MP treatment group(P all<0.01). There were high positive cells in IL-1β expression in AC.YVAD.CMK group at 24 h and 72 h postoperatively compared with MP treatment group(P all<0.01). Conclusion Caspase-1 inhibitor can significantly reduce the expression of Caspase-1,IL-1β and IL-18 after spinal cord injury,and has a certain targeted inhibitory effect on secondary injury after SCI,which may play a certain role in the repair of spinal cord injury.

参考文献/References:

[1] Vezzani A,Balosso S,Maroso M,et al. ICE/caspase 1 inhibitors and IL-1beta receptor antagonists as potential therapeutics in epilepsy[J]. Current Opinion in Investigational Drugs,2010,11(1):43-50.
[2] 郭强,孔毅荣,付玲,等. 炎性体的研究进展[J]. 军事医学科学院院刊,2007,31(5):490-493.
[3] Saha N,Moldovan F,et al. Interleukin-1beta-converting enzyme/caspase-1 in human osteoarthritic tissues:localization and role in the maturation of interleukin-1beta and interleukin-18[J]. Arthritis Rheum,1999,42(8):1577-1587.
[4] 樊涛,丁惠强,王拯,等. Caspase-1及其激活的IL-18在大鼠急性脊髓组织损伤后的表达及意义[J]. 宁夏医科大学学报,2009,31(3):295-299.
[5] 杨新明,成垚昱,张振梁,等. 甲强龙在骨髓间充质干细胞治疗大鼠脊髓损伤中的作用及对肿瘤坏死因子-α和白细胞介素-1β表达的影响[J]. 中国医学科学院学报,2017,39(5):617-624.
[6] Liu JT,Zhang S,Gu B,et al. Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury[J]. Neural Regen Res,2017,12(9):1507-1518.
[7] Tewari M,Monika N,Varghse RK,et al. Astrocytes mediate HIV-1 Tat induced neuronal damage via ligand-gated Ion channel P2X7R[J]. J Neurochem,2015,132(4):464-476.
[8] 黄星球,廖绪强,史成龙,等. 甲基强的松龙抑制脊髓损伤模型大鼠小胶质细胞活化介导的炎症[J]. 中国组织工程研究,2019,23(19):3050-3055.
[9] Liang HS,Sun Y,Gao AL,et al. Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats[J]. IntImmunopharmacol,2019,75:1057-1071.
[10] Xu XE,Liu L,Wang YC,et al. Caspase-1 inhibitor exerts brain-protective effects against Sepsis-associated encephalopathy and cognitive impairments in a mouse model of Sepsis[J]. Brain Behav Immun,2019,80:859-870.
[11] 邱美光,李占飞,白祥军. Caspase-1抑制剂对大鼠外伤性脑损伤后脑水肿、神经细胞凋亡和IL-18表达的影响[J]. 中国临床神经外科杂志,2008,13(9):546-549.
[12] Dapaah-Siakwan F,Zambrano R,Luo SH,et al. Caspase-1 inhibition attenuates hyperoxia-induced lung and brain injury in neonatal mice[J]. AmJRespir Cell MolBiol,2019,61(3):341-354.

相似文献/References:

[1]任彬彬,李国莉,刘贺荣,等.大鼠慢性酒精性肝损伤动物模型的建立[J].宁夏医科大学学报,2012,(01):95.
[2]肖成明,张 红,曹 丹,等.米非司酮对子宫内膜异位症大鼠内膜OPN 及MMP-9表达的影响[J].宁夏医科大学学报,2012,(01):17.
 XIAO Cheng-ming,ZHANG Hong,CAO Dan,et al.Effect of Mifepristone on OPN and MMP-9 in Endometriosis Models of Rats[J].Ningxia Medical University,2012,(02):17.
[3]常 越,安 欣,张建中,等.自发性高血压大鼠心肌重构与p38MAPK关系的研究[J].宁夏医科大学学报,2013,(12):1339.
 CHANG Yue,AN Xin,ZHANG Jianzhong,et al.The Relationship between p38MAPK and Myocardial Remodeling in Spontaneously Hypertensive Rats[J].Ningxia Medical University,2013,(02):1339.
[4]戴广政,宋琦如,赵 萌,等.中波紫外线照射对大鼠血清IL-1、IL-2及溶菌酶含量的影响[J].宁夏医科大学学报,2013,(12):1326.
 The Influence of UVB Irradiation on Serum IL-,IL- and Lysozyme Contents of Rats.The Influence of UVB Irradiation on Serum IL-1, IL-2 and Lysozyme Contents of Rats[J].Ningxia Medical University,2013,(02):1326.
[5]高 鹏,张 春,赵 巍,等.重组腺病毒载体对大鼠胶质瘤细胞转染效率的影响[J].宁夏医科大学学报,2013,(12):1322.
 GAO Peng,ZHANG Chun,ZHAO Wei,et al.Infection Efficiency of Rat C6 Cells Infected with Recombinant Adenovirus Vectors[J].Ningxia Medical University,2013,(02):1322.
[6]马赞林,王 毅,马莉琼,等.大鼠横型腹直肌缺血肌皮瓣模型血运特点[J].宁夏医科大学学报,2013,(11):1226.
 MA Zanlin,WANG Yi,MA Liqiong,et al.Characteristics of Blood Supply of Transverse Rectus Abdominis Myocutaneous Flap in the Rat Model[J].Ningxia Medical University,2013,(02):1226.
[7]赵东旭,闫生亮,吴兴临,等.枸杞多糖对大鼠骨折愈合过程中BMP-2表达的影响[J].宁夏医科大学学报,2013,(05):506.
 ZHAO Dong-xu,YAN Sheng-liang,WU Xing-lin,et al.Influence of LBP on Expression of BMP-2 during the Process of Fracture Healing in Rats[J].Ningxia Medical University,2013,(02):506.
[8]董俭达,景 丽,刘 全,等.异常光照制对大鼠血压和体重的影响[J].宁夏医科大学学报,2013,(03):248.
 DONG Jian-da,JIN Li,LIU Quan,et al.Effects of Abnormal Light Regimen on Blood Pressure and Body Weight in Rats[J].Ningxia Medical University,2013,(02):248.
[9]徐向钊,张冬梅,郎淑慧,等.静脉注射胺碘酮对急性心肌缺血大鼠血流动力学的影响[J].宁夏医科大学学报,2013,(02):137.
 XU Xiang-zhao,ZHANG Dong-mei,LANG Shu-hui,et al.Effect of Intravenous Administration of Amiodarone on The Hemodynamics in Rats with Acute Myocardial Ischemic[J].Ningxia Medical University,2013,(02):137.
[10]王春生,孟尽海,吴 燕,等.丙泊酚对大鼠急性脊髓损伤早期的影响[J].宁夏医科大学学报,2013,(09):964.
 WANG Chunsheng,MENG Jinhai,WU Yan,et al.Effects of Propofol on Acute Early Spinal Cord Injury in Rats[J].Ningxia Medical University,2013,(02):964.

备注/Memo

备注/Memo:
收稿日期:2020-03-16
基金项目:宁夏医科大学科学研究基金资助项目(XM2016047)
作者简介:锁志刚(1979—),男,副主任医师,硕士,研究方向:脊柱脊髓损伤。E-mail:szg.123456789@163.com
更新日期/Last Update: 1900-01-01