中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2010年
2期
138-142
,共5页
朱薇薇%赵红洋%温天莲%郭爱丽%毕玫荣
硃薇薇%趙紅洋%溫天蓮%郭愛麗%畢玫榮
주미미%조홍양%온천련%곽애려%필매영
大鼠%新生%缺氧缺血%脑%Nogo受体拮抗剂
大鼠%新生%缺氧缺血%腦%Nogo受體拮抗劑
대서%신생%결양결혈%뇌%Nogo수체길항제
Rats%Newborn%Hypoxia-ischemia%Brain%Nogo receptor antagonists
目的 探讨缺氧缺血性脑损伤(HIBI)新生大鼠脑Nogo受体表达及Nogo受体拮抗剂NEP1-40的脑保护作用.方法 采用随机数字表法将80只7日龄大鼠随机分为对照组、HIBD组、GM-1组和NEP1-40组.正常对照组及HIBD模型组腹腔注射生理盐水0.25 ml/kg,NEP1-40组、GM-1组分别注射5 g/L NEP1-40、2.5μl/d,40 g/LGM-10.25 ml/(kg·d),视分组情况连用3 d或7 d.采用原位杂交法检测各组大鼠脑组织24 h、72 h及7 d NgR-mRNA表达水平,透射电镜观测其脑神经元与轴突的变化.多个样本率总体比较采用χ~2检验,组间均数多重比较采用LSD-t检验,数据均采用SPSS10.0统计软件包处理,以P<0.05有统计学意义.结果 HIBD组、GM-1组和NEP1-40组各时期脑组织NgR水平均低于对照组(t值分别为5.48、6.11、6.96、8.24、5.99和5.34,均P<0.05),三组间24 h NgR水平差异无统计学意义(t值分别为1.48、2.76和1.29,均P>0.05),而NEP1-40组72 h与7 d NgR水平低于同时期HIBD组、GM-1组;GM-1治疗后脑组织神经元得到不同程度的修复,而NEP1-40治疗后神经元修复良好,轴突再生明显.结论 缺氧缺血性脑损伤后脑NsR水平下调,NEP1-40可促进脑损伤的修复,发挥脑保护作用.
目的 探討缺氧缺血性腦損傷(HIBI)新生大鼠腦Nogo受體錶達及Nogo受體拮抗劑NEP1-40的腦保護作用.方法 採用隨機數字錶法將80隻7日齡大鼠隨機分為對照組、HIBD組、GM-1組和NEP1-40組.正常對照組及HIBD模型組腹腔註射生理鹽水0.25 ml/kg,NEP1-40組、GM-1組分彆註射5 g/L NEP1-40、2.5μl/d,40 g/LGM-10.25 ml/(kg·d),視分組情況連用3 d或7 d.採用原位雜交法檢測各組大鼠腦組織24 h、72 h及7 d NgR-mRNA錶達水平,透射電鏡觀測其腦神經元與軸突的變化.多箇樣本率總體比較採用χ~2檢驗,組間均數多重比較採用LSD-t檢驗,數據均採用SPSS10.0統計軟件包處理,以P<0.05有統計學意義.結果 HIBD組、GM-1組和NEP1-40組各時期腦組織NgR水平均低于對照組(t值分彆為5.48、6.11、6.96、8.24、5.99和5.34,均P<0.05),三組間24 h NgR水平差異無統計學意義(t值分彆為1.48、2.76和1.29,均P>0.05),而NEP1-40組72 h與7 d NgR水平低于同時期HIBD組、GM-1組;GM-1治療後腦組織神經元得到不同程度的脩複,而NEP1-40治療後神經元脩複良好,軸突再生明顯.結論 缺氧缺血性腦損傷後腦NsR水平下調,NEP1-40可促進腦損傷的脩複,髮揮腦保護作用.
목적 탐토결양결혈성뇌손상(HIBI)신생대서뇌Nogo수체표체급Nogo수체길항제NEP1-40적뇌보호작용.방법 채용수궤수자표법장80지7일령대서수궤분위대조조、HIBD조、GM-1조화NEP1-40조.정상대조조급HIBD모형조복강주사생리염수0.25 ml/kg,NEP1-40조、GM-1조분별주사5 g/L NEP1-40、2.5μl/d,40 g/LGM-10.25 ml/(kg·d),시분조정황련용3 d혹7 d.채용원위잡교법검측각조대서뇌조직24 h、72 h급7 d NgR-mRNA표체수평,투사전경관측기뇌신경원여축돌적변화.다개양본솔총체비교채용χ~2검험,조간균수다중비교채용LSD-t검험,수거균채용SPSS10.0통계연건포처리,이P<0.05유통계학의의.결과 HIBD조、GM-1조화NEP1-40조각시기뇌조직NgR수평균저우대조조(t치분별위5.48、6.11、6.96、8.24、5.99화5.34,균P<0.05),삼조간24 h NgR수평차이무통계학의의(t치분별위1.48、2.76화1.29,균P>0.05),이NEP1-40조72 h여7 d NgR수평저우동시기HIBD조、GM-1조;GM-1치료후뇌조직신경원득도불동정도적수복,이NEP1-40치료후신경원수복량호,축돌재생명현.결론 결양결혈성뇌손상후뇌NsR수평하조,NEP1-40가촉진뇌손상적수복,발휘뇌보호작용.
Objective The hypoxic-ischemic encephalopathy caused by asphyxia in peripartum is a serious disease in newborn infants, with a high disability and mortality rate. Lack of regenerative ability in central nervous system after injury is considered as the fundamental cause. However, in recent years many studies have revealed that there are myelin-associated neurite growth inhibitory factors that exert inhibiting effect through the Nago receptor (NgR). This study aimed to investigate the expression level of NgR and the possible neuroprotective effect of NEP1-40 in newborn rats with hypoxic ischemic brain damage (HIBD). Method Eighty healthy Wistar rats aged 7 days were randomly divided into 4 groups;8 in control group, 24 in HIBD model group,24 in GM-1 group and 24 in NEP1-40 group. The rats of the control group and HIBD group were injected with normal saline (0.25 ml/kg) intraperitoneally, while those in NEP1-40 group and GM-1 group with NEP1-40 12.5μg/,GM-1 10mg/(kg·d) for continuous 3 days of 72-hour group or 7 days of 168-hour group, respectively. In situ hybridization was adopted for detecting the expression of NgR in the brain of the rats at the time point of 24 hours, 72 hours and 7 days. Meanwhile histopathological changes of neurons and axon were detected by transmission electron microscopy (TEM). The SPSS statistical software package for Windows, version 10.0, was used to run Chi-square tests and least significance difference(LSD-t) on the data presented, and P value of less than 0.05 was regarded as statistically significant. Result The expression level of Nogo-A receptor in the control group was higher than that of the other groups at different time point (t value was 5.48, 6.11, 6.96, 8.24, 5.99 and 5.34, respectively, and all P values were less than 0.05 ). There were no significant differences in Nngo-A receptor level among the HIBD group, the GM-1 group and the NEP1-40 at 24 hours ( t was 1.48, 2.76 and 1.29, respectively, and all P>0.05) ,while the expression of Nogo-A receptor of NEP1-40 at 72 hours and 7 days was lower than that of the HIBD group and the GM-1 group at the same time point, respectively (all P<0.05). Repair of neurons in damaged brain to some extent was found after GM-1 treatment and satisfactory repair of neurons and axon regeneration was obtained with NEP1-40 administration as shown by TEM. Conclusion Hypoxic ischemic brain damage can down-regulate the expression of Nogo-A receptor in the central nervous system. NEP1-40 contributes to the regeneration of axon and repair of brain damage, thus exerts neuroprotective effect.