中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
5期
628-631,632
,共5页
万晓红%王雁%赵国良%陈华梅%邵建林
萬曉紅%王雁%趙國良%陳華梅%邵建林
만효홍%왕안%조국량%진화매%소건림
血红素氧合酶-1%缺血/再灌注损伤%海马%蛋白%蛋白转导域%11 个精氨酸残基%凋亡
血紅素氧閤酶-1%缺血/再灌註損傷%海馬%蛋白%蛋白轉導域%11 箇精氨痠殘基%凋亡
혈홍소양합매-1%결혈/재관주손상%해마%단백%단백전도역%11 개정안산잔기%조망
hemeoxygenase-1%ischemia-reperfusion%hippocampus%protein%protein transduction domain%11 consecutive arginine residues%apoptosis
目的:评价血红素氧合酶-1(HO-1)蛋白转导对脑缺血/再灌注损伤沙土鼠海马神经元的影响。方法构建11R (11个精氨酸残基)-HO-1蛋白,50只沙土鼠随机分为5组(n=10):脑缺血/再灌注组(C组),沙土鼠行脑缺血/再灌注损伤。脑缺血/再灌注+生理盐水组(S组)、脑缺血/再灌注+11R组(R组)、脑缺血/再灌注+5 mg·kg-111R-HO-1组(H1组)和脑缺血/再灌注+25 mg·kg-111R-HO-1组(H2组),各组沙土鼠腹腔分别注射5 mg·kg-1生理盐水、5 mg·kg-111R蛋白、5 mg·kg-111R-HO-1蛋白或25 mg· kg-111R-HO-1蛋白,3 h后行脑缺血/再灌注损伤。24 h后取沙土鼠海马,电镜下观察海马组织线粒体的变化,检测海马神经元凋亡、Caspase-3和HO-1蛋白表达、cAMP水平。结果 C组、S组和R组3组间海马神经元线粒体变性率、神经元凋亡率、Caspase-3和HO-1蛋白表达、cAMP水平变化无差异(P>0.05);H1组海马神经元线粒体变性率降低、神经元凋亡率降低、Caspase-3蛋白表达下调、HO-1蛋白表达上调、cAMP水平升高(vs C组、S组和R组,P<0.01);H2组海马神经元线粒体变性率降低、神经元凋亡率降低、Caspase-3蛋白表达下调、HO-1蛋白表达上调、cAMP水平升高( vs H1组,P<0.01)。结论 HO-1蛋白转导减轻了脑缺血/再灌注沙土鼠海马神经元的损伤。
目的:評價血紅素氧閤酶-1(HO-1)蛋白轉導對腦缺血/再灌註損傷沙土鼠海馬神經元的影響。方法構建11R (11箇精氨痠殘基)-HO-1蛋白,50隻沙土鼠隨機分為5組(n=10):腦缺血/再灌註組(C組),沙土鼠行腦缺血/再灌註損傷。腦缺血/再灌註+生理鹽水組(S組)、腦缺血/再灌註+11R組(R組)、腦缺血/再灌註+5 mg·kg-111R-HO-1組(H1組)和腦缺血/再灌註+25 mg·kg-111R-HO-1組(H2組),各組沙土鼠腹腔分彆註射5 mg·kg-1生理鹽水、5 mg·kg-111R蛋白、5 mg·kg-111R-HO-1蛋白或25 mg· kg-111R-HO-1蛋白,3 h後行腦缺血/再灌註損傷。24 h後取沙土鼠海馬,電鏡下觀察海馬組織線粒體的變化,檢測海馬神經元凋亡、Caspase-3和HO-1蛋白錶達、cAMP水平。結果 C組、S組和R組3組間海馬神經元線粒體變性率、神經元凋亡率、Caspase-3和HO-1蛋白錶達、cAMP水平變化無差異(P>0.05);H1組海馬神經元線粒體變性率降低、神經元凋亡率降低、Caspase-3蛋白錶達下調、HO-1蛋白錶達上調、cAMP水平升高(vs C組、S組和R組,P<0.01);H2組海馬神經元線粒體變性率降低、神經元凋亡率降低、Caspase-3蛋白錶達下調、HO-1蛋白錶達上調、cAMP水平升高( vs H1組,P<0.01)。結論 HO-1蛋白轉導減輕瞭腦缺血/再灌註沙土鼠海馬神經元的損傷。
목적:평개혈홍소양합매-1(HO-1)단백전도대뇌결혈/재관주손상사토서해마신경원적영향。방법구건11R (11개정안산잔기)-HO-1단백,50지사토서수궤분위5조(n=10):뇌결혈/재관주조(C조),사토서행뇌결혈/재관주손상。뇌결혈/재관주+생리염수조(S조)、뇌결혈/재관주+11R조(R조)、뇌결혈/재관주+5 mg·kg-111R-HO-1조(H1조)화뇌결혈/재관주+25 mg·kg-111R-HO-1조(H2조),각조사토서복강분별주사5 mg·kg-1생리염수、5 mg·kg-111R단백、5 mg·kg-111R-HO-1단백혹25 mg· kg-111R-HO-1단백,3 h후행뇌결혈/재관주손상。24 h후취사토서해마,전경하관찰해마조직선립체적변화,검측해마신경원조망、Caspase-3화HO-1단백표체、cAMP수평。결과 C조、S조화R조3조간해마신경원선립체변성솔、신경원조망솔、Caspase-3화HO-1단백표체、cAMP수평변화무차이(P>0.05);H1조해마신경원선립체변성솔강저、신경원조망솔강저、Caspase-3단백표체하조、HO-1단백표체상조、cAMP수평승고(vs C조、S조화R조,P<0.01);H2조해마신경원선립체변성솔강저、신경원조망솔강저、Caspase-3단백표체하조、HO-1단백표체상조、cAMP수평승고( vs H1조,P<0.01)。결론 HO-1단백전도감경료뇌결혈/재관주사토서해마신경원적손상。
Aim To investigate the effect of transduct-ed-hemeoxygenase-1 ( HO-1 ) protein on brain ischemi-a-reperfusion ( I/R ) rat hippocampal neurons injury. Methods 11 R ( arginine residues )-fused HO-1 pro-tein was established and 50 male Mongolian gerbils were randomly divided into 5 groups ( n=10 ):I/R ( control group ) , I/R + 5 mg · kg-1 saline group ( group S ) , I/R + 5 mg · kg-1 11 R group ( group R), I/R + 5mg·kg-1 11R-HO-1 group (group H1) and I/R + 25 mg · kg-1 11 R-HO-1 group ( group H2). For I/R experiments, ischemia was induced for 5 min by occluding the common carotid arteries bilater-ally with aneurysm clips under Ketamine anesthesia. The experiment was conducted after the neurons were intraperitoneally injected with 5mg·kg-1 saline,11R , 11R-HO-1,or 25mg · kg-1 11R-HO-1 for 3 h. The rats were killed after 24h of reperfusion. Hippocampus was removed immediately for determination of cAMP level, neuronal apoptotic rate, and expression of HO-1 and Caspase-3 protein, mitochondria was observed un-der electron microscope. Results Among group C, group S and group R,there were no differences in the expressions of HO-1, Caspase-3 protein, cAMP level , neuronal apoptotic rate and mitochondria damage ( P>0. 05). Compared with group C, group S and group R, the expression of HO-1 protein was up-regulated, the expression of Caspase-3 protein was down-regula-ted, cAMP level increased, the apoptotic rate was sig-nificantly decreased and mitochondria damage de-creased in group H1 ( P < 0. 01 ) . Compared with group H1 , the expression of HO-1 protein was up-regu-lated, the expression of Caspase-3 protein was down-regulated, cAMP level increased, the apoptotic rate was significantly decreased and mitochondria damage decreased in group H2 ( P <0. 01 ) . Conclusion Transducted-HO-1 protein can attenuate brain ischemi-a-reperfusion rat hippocampal neurons injury.