Caspase-1抑制剂在大鼠脊髓损伤后的靶点作用  

Targeting of Caspase-1 Inhibitors after Spinal Cord Injury in Rats

作　　者：锁志刚[1] 丁惠强[1] 费乐 黑龙[1] 戈朝晖[1] 马宗军[1] 陈霄雷 SUO Zhigang;DING Huiqiang;FEI Le;HEI Long;GE Zhaohui;MA Zongjun;CHEN Xiaolei(Department of Spinal Orthopedics,the General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院脊柱骨科,银川750004

出　　处：《宁夏医科大学学报》2021年第2期119-123,共5页Journal of Ningxia Medical University

基　　金：宁夏医科大学科学研究基金资助项目(XM2016047)。

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。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.

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 

分 类 号：R744[医药卫生—神经病学与精神病学]