国际药学研究杂志
國際藥學研究雜誌
국제약학연구잡지
INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH
2014年
6期
698-702,706
,共6页
邓诗源%王卓强%徐震%马超
鄧詩源%王卓彊%徐震%馬超
산시원%왕탁강%서진%마초
脊髓钳夹伤%Basso小鼠后肢的行为学评分%白细胞介素(IL)-17%IL-17中和抗体
脊髓鉗夾傷%Basso小鼠後肢的行為學評分%白細胞介素(IL)-17%IL-17中和抗體
척수겸협상%Basso소서후지적행위학평분%백세포개소(IL)-17%IL-17중화항체
spinal cord injury by clamping%BMS score%interleukin%IL-17 neutralizing antibody
目的探讨C57小鼠脊髓钳夹区IL-17表达的变化规律,为临床治疗脊髓损伤(SCI)提供新的靶点。方法雄性C57BL/6小鼠随机分为3组,即SCI模型组、假手术组和IL-17中和抗体组。模型组制作小鼠脊髓钳夹模型,假手术组只剪开硬脊膜不伤及脊髓;IL-17中和抗体组在脊髓钳夹1 h即刻尾静脉给予IL-17中和抗体。小鼠后肢功能变化按Basso提出的小鼠后肢行为学评分(BMS)于1~7 d进行,实时荧光定量PCR检测脊髓损伤区IL-17 mRNA各时间点表达变化,HE染色观察各组小鼠脊髓损伤第7天脊髓组织病理学变化。结果小鼠SCI后行为学显示,假手术组小鼠BMS在1~7 d均为9分;模型组小鼠BMS第1天为0分、第7天达2.9分;IL-17中和抗体组小鼠BMS第1天为0分、损伤第7天BMS评分达3.5分。实时荧光定量PCR显示,损伤区IL-17 mRNA的表达在损伤3 h升至最高,与假手术组相比具有统计学差异(P<0.05),随后其表达水平开始下降,其他时间点与假手术组相比没有统计学差异(P>0.05),损伤第7天IL-17 mRNA的表达最低。HE染色结果显示,SCI后7 d,假手术组小鼠脊髓组织形态完整;模型组小鼠大量神经细胞坏死、凋亡,大量细胞空泡状形成;中和抗体组小鼠部分神经元核固缩,有细胞空泡状形成,但部分细胞仍保持完整形态。结论 IL-17参与了SCI的继发性免疫炎症进程,可能是SCI治疗的干预靶点。
目的探討C57小鼠脊髓鉗夾區IL-17錶達的變化規律,為臨床治療脊髓損傷(SCI)提供新的靶點。方法雄性C57BL/6小鼠隨機分為3組,即SCI模型組、假手術組和IL-17中和抗體組。模型組製作小鼠脊髓鉗夾模型,假手術組隻剪開硬脊膜不傷及脊髓;IL-17中和抗體組在脊髓鉗夾1 h即刻尾靜脈給予IL-17中和抗體。小鼠後肢功能變化按Basso提齣的小鼠後肢行為學評分(BMS)于1~7 d進行,實時熒光定量PCR檢測脊髓損傷區IL-17 mRNA各時間點錶達變化,HE染色觀察各組小鼠脊髓損傷第7天脊髓組織病理學變化。結果小鼠SCI後行為學顯示,假手術組小鼠BMS在1~7 d均為9分;模型組小鼠BMS第1天為0分、第7天達2.9分;IL-17中和抗體組小鼠BMS第1天為0分、損傷第7天BMS評分達3.5分。實時熒光定量PCR顯示,損傷區IL-17 mRNA的錶達在損傷3 h升至最高,與假手術組相比具有統計學差異(P<0.05),隨後其錶達水平開始下降,其他時間點與假手術組相比沒有統計學差異(P>0.05),損傷第7天IL-17 mRNA的錶達最低。HE染色結果顯示,SCI後7 d,假手術組小鼠脊髓組織形態完整;模型組小鼠大量神經細胞壞死、凋亡,大量細胞空泡狀形成;中和抗體組小鼠部分神經元覈固縮,有細胞空泡狀形成,但部分細胞仍保持完整形態。結論 IL-17參與瞭SCI的繼髮性免疫炎癥進程,可能是SCI治療的榦預靶點。
목적탐토C57소서척수겸협구IL-17표체적변화규률,위림상치료척수손상(SCI)제공신적파점。방법웅성C57BL/6소서수궤분위3조,즉SCI모형조、가수술조화IL-17중화항체조。모형조제작소서척수겸협모형,가수술조지전개경척막불상급척수;IL-17중화항체조재척수겸협1 h즉각미정맥급여IL-17중화항체。소서후지공능변화안Basso제출적소서후지행위학평분(BMS)우1~7 d진행,실시형광정량PCR검측척수손상구IL-17 mRNA각시간점표체변화,HE염색관찰각조소서척수손상제7천척수조직병이학변화。결과소서SCI후행위학현시,가수술조소서BMS재1~7 d균위9분;모형조소서BMS제1천위0분、제7천체2.9분;IL-17중화항체조소서BMS제1천위0분、손상제7천BMS평분체3.5분。실시형광정량PCR현시,손상구IL-17 mRNA적표체재손상3 h승지최고,여가수술조상비구유통계학차이(P<0.05),수후기표체수평개시하강,기타시간점여가수술조상비몰유통계학차이(P>0.05),손상제7천IL-17 mRNA적표체최저。HE염색결과현시,SCI후7 d,가수술조소서척수조직형태완정;모형조소서대량신경세포배사、조망,대량세포공포상형성;중화항체조소서부분신경원핵고축,유세포공포상형성,단부분세포잉보지완정형태。결론 IL-17삼여료SCI적계발성면역염증진정,가능시SCI치료적간예파점。
Objective To investigate the mechanism of expression of interlenkin (IL)-17 in C57 mice′s spinal cord clamp area,and to provide new targets for clinical treatment of spinal cord injury (SCI). Methods Male C57BL/6 mice were randomly divided into three groups. In the spinal cord injury group,mice were made into spinal cord clamp model. In the sham surgery group, the dura was cut without injuring the spinal cord. The IL-17 neutralizing antibody group received IL-17 neutralizing antibody injection through the cadual vein at 1 hour after the spinal cord clamp . Mouse scale for locomotion (BMS)was applied to evaluate the mice's behavior change of hindlimb in 1-7 days,the real time fluorescent quantitative PCR was used to detect the change in the expression of spinal cord injury district TNF-αmRNA each time,HE staining was conducted to detect the morphological changes of spinal cord injury of the sham surgery group,the spinal cord injury group and the IL-17 neutralizing antibody group at the 7th days. Results After spinal cord injury,the mice's BMS score were 9 in the sham surgery group;in the model of spinal cord injury group,the mice's BMS score were 0 on the 1st day,and 2.9 on the 7th day. In the IL-17 neutralizing antibody group,the mice's BMS score were 0 on the 1st day,and 3.5 on the 7th day. The expression of IL-17 mRNA in the injury area peaked at the 3rd hour,which showed statistical difference when compared with sham surgery group (P<0.05),and then decreased. In other times,it had no statistical difference when compared with sham surgery group (P>0.05),and the expression of IL-17 mRNA reduced the lowest levels on the 7th day. The 7th day following spinal cord injury,mice's spinal cord tissue was complete normal in the sham surgery group. In the spinal cord injury group,a large number of mice's nerve cells were necrotic, a lot of cells formed vacuolated. In the IL-17 neutralizing antibody group, part of mice's nuclear neurons were shrinking, cells formed vacuolated, but part of cells remained morphologically complete. Conclusion IL-17 is involved in secondary immune inflammatory process of spinal cord injury, it may be targets for intervention in the treatment of spinal cord injury.