中华神经医学杂志
中華神經醫學雜誌
중화신경의학잡지
Chinese Journal of Neuromedicine
2015年
8期
810-816
,共7页
李琴%程永梅%毕明俊%康海%邹勇
李琴%程永梅%畢明俊%康海%鄒勇
리금%정영매%필명준%강해%추용
一氧化碳中毒%依达拉奉%细胞凋亡%氧化应激损伤%血红素加氧酶-1%转录因子NF-E2相关因子2
一氧化碳中毒%依達拉奉%細胞凋亡%氧化應激損傷%血紅素加氧酶-1%轉錄因子NF-E2相關因子2
일양화탄중독%의체랍봉%세포조망%양화응격손상%혈홍소가양매-1%전록인자NF-E2상관인자2
Carbon monoxide poisoning%Edaravone%Apoptosis%Oxidative stress%Heme oxygenase-1%Nuclear factor erythrocyte two related factor-2
目的 探讨依达拉奉对急性一氧化碳(CO)中毒后脑组织损伤的神经保护作用及其作用机制. 方法 90只SD大鼠按随机数字表法分为正常组、中毒组和治疗组,每组30只.中毒组和治疗组大鼠应用高压氧舱法建立急性CO中毒模型并给予高压氧治疗,治疗组在此基础上给予腹腔注射依达拉奉(10 mg/kg).各组大鼠分别在中毒后1d、2d、7d应用TUNEL染色和RT-PCR法检测脑组织细胞凋亡情况及凋亡相关基因[B淋巴细胞瘤-2(Bcl-2)、Box] mRNA表达,应用免疫组化染色和Western blotting检测脑组织血红素加氧酶-1(HO-1)和转录因子NF-E2相关因子2(NRF-2)阳性细胞及蛋白表达. 结果 与正常组比较,中毒组和治疗组凋亡细胞数明显增高,差异有统计学意义(P＜0.05);与中毒组比较,治疗组凋亡细胞数相对减低,差异有统计学意义(P＜0.05).中毒组Bcl-2 mRNA和Bax mRNA表达水平较正常组明显升高,差异有统计学意义(P＜0.05);与中毒组比较,治疗组Bcl-2 mRNA表达水平明显增高,而Bax mRNA表达水平明显减低,Bcl-2mRN A/ Bax mRNA的比值明显增高,差异有统计学意义(P＜0.05).中毒组脑组织HO-1和NRF-2阳性细胞及蛋白表达水平明显高于正常组,治疗组脑组织HO-1和NRF-2阳性细胞及蛋白表达水平明显高于中毒组,差异均有统计学意义(P＜0.05). 结论 依达拉奉可能通过参与NRF-2/HO-1途径激活对抗氧化应激损伤,抑制神经细胞凋亡,从而对急性CO中毒后脑损伤发挥神经保护作用.
目的 探討依達拉奉對急性一氧化碳(CO)中毒後腦組織損傷的神經保護作用及其作用機製. 方法 90隻SD大鼠按隨機數字錶法分為正常組、中毒組和治療組,每組30隻.中毒組和治療組大鼠應用高壓氧艙法建立急性CO中毒模型併給予高壓氧治療,治療組在此基礎上給予腹腔註射依達拉奉(10 mg/kg).各組大鼠分彆在中毒後1d、2d、7d應用TUNEL染色和RT-PCR法檢測腦組織細胞凋亡情況及凋亡相關基因[B淋巴細胞瘤-2(Bcl-2)、Box] mRNA錶達,應用免疫組化染色和Western blotting檢測腦組織血紅素加氧酶-1(HO-1)和轉錄因子NF-E2相關因子2(NRF-2)暘性細胞及蛋白錶達. 結果 與正常組比較,中毒組和治療組凋亡細胞數明顯增高,差異有統計學意義(P＜0.05);與中毒組比較,治療組凋亡細胞數相對減低,差異有統計學意義(P＜0.05).中毒組Bcl-2 mRNA和Bax mRNA錶達水平較正常組明顯升高,差異有統計學意義(P＜0.05);與中毒組比較,治療組Bcl-2 mRNA錶達水平明顯增高,而Bax mRNA錶達水平明顯減低,Bcl-2mRN A/ Bax mRNA的比值明顯增高,差異有統計學意義(P＜0.05).中毒組腦組織HO-1和NRF-2暘性細胞及蛋白錶達水平明顯高于正常組,治療組腦組織HO-1和NRF-2暘性細胞及蛋白錶達水平明顯高于中毒組,差異均有統計學意義(P＜0.05). 結論 依達拉奉可能通過參與NRF-2/HO-1途徑激活對抗氧化應激損傷,抑製神經細胞凋亡,從而對急性CO中毒後腦損傷髮揮神經保護作用.
목적 탐토의체랍봉대급성일양화탄(CO)중독후뇌조직손상적신경보호작용급기작용궤제. 방법 90지SD대서안수궤수자표법분위정상조、중독조화치료조,매조30지.중독조화치료조대서응용고압양창법건립급성CO중독모형병급여고압양치료,치료조재차기출상급여복강주사의체랍봉(10 mg/kg).각조대서분별재중독후1d、2d、7d응용TUNEL염색화RT-PCR법검측뇌조직세포조망정황급조망상관기인[B림파세포류-2(Bcl-2)、Box] mRNA표체,응용면역조화염색화Western blotting검측뇌조직혈홍소가양매-1(HO-1)화전록인자NF-E2상관인자2(NRF-2)양성세포급단백표체. 결과 여정상조비교,중독조화치료조조망세포수명현증고,차이유통계학의의(P＜0.05);여중독조비교,치료조조망세포수상대감저,차이유통계학의의(P＜0.05).중독조Bcl-2 mRNA화Bax mRNA표체수평교정상조명현승고,차이유통계학의의(P＜0.05);여중독조비교,치료조Bcl-2 mRNA표체수평명현증고,이Bax mRNA표체수평명현감저,Bcl-2mRN A/ Bax mRNA적비치명현증고,차이유통계학의의(P＜0.05).중독조뇌조직HO-1화NRF-2양성세포급단백표체수평명현고우정상조,치료조뇌조직HO-1화NRF-2양성세포급단백표체수평명현고우중독조,차이균유통계학의의(P＜0.05). 결론 의체랍봉가능통과삼여NRF-2/HO-1도경격활대항양화응격손상,억제신경세포조망,종이대급성CO중독후뇌손상발휘신경보호작용.
Objective To evaluate the neuroprotective effect of edaravone on brain tissues after acute carbon monoxide (CO) poisoning and explore its mechanism.Methods Ninety Sprague-Dawley rats were randomly selected as normal control group,poisoning group and treatment group (n=30).Rats in the poisoning group and treatment group were established animal models of acute CO poisoning with hyperbaric chamber method and received hyperbaric oxygen therapy.The rats in the treatment group were given intraperitoneal injection ofedaravone (10 mg/kg) additionally.TUNEL and real time-PCR were used to detect the cell apoptosis and their apoptosis-related gene expressions (Bcl-2 and Bax mRNA) in brain tissues 1,2 and 7 d after CO poisoning in each group.Immunohistochemistry and Western blotting were used to observe the positive cells and protein changes of heme oxygenase-1 (HO-1) and nuclear factor erythrocyte two related factors-2 (NRF-2).Results The apoptosis cell number in the poisoning group and the treatment group was significantly increased as compared with that in the normal control group (P＜0.05);that in the treatment group was relatively fewer than that in the poisoning group with significant differences (P＜0.05).As compared with those in the normal control group,the Bcl-2 and Bax mRNA expressions in the poisoning group were obviously up-regulated with significant difference (P＜0.05);the Bcl-2 mRNA level was significantly increased,the Bax mRNA level was signficantly down-regulated,and the ratio ofBcl-2 mRNA/Bax mRNA was notablyly increased in the treatment group as compared with those in the poisoning group (P＜0.05).The positive cells and HO-1 and NRF-2 proteins in the brain tissues of the poisoning group were significantly higher than those in the normal group (P＜0.05);those in the treatment group were obviously increased as compared with those in the poisoning group (P＜0.05).Conclusion Edaravone might be partly associated with activation of NRF-2/HO-1 pathway to counteract oxidative stress damage,inhibit neuronal apoptosis,and play a neuroprotective role in brain damage after acute CO poisoning.
