国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2013年
3期
191-196
,共6页
脑出血%羟甲基戊二酰基CoA还原酶抑制剂%阿托伐他汀%细胞色素c组%细胞凋亡%大鼠
腦齣血%羥甲基戊二酰基CoA還原酶抑製劑%阿託伐他汀%細胞色素c組%細胞凋亡%大鼠
뇌출혈%간갑기무이선기CoA환원매억제제%아탁벌타정%세포색소c조%세포조망%대서
Cerebral Hemorrhage%Hydroxymethylglutaryl-CoA Reductase Inhibitors%Atorvastatin%Cytochrome c Group%Apoptosis%Rats
目的 探讨阿托伐他汀对大鼠脑出血后血肿周围组织细胞凋亡和细胞色素c(Cytochrome c,CytC)表达的影响.方法 108只雄性Sprague-Dawley大鼠随机分为假手术组、生理盐水对照组和阿托伐他汀组(每组36只),各组再分为6h、12 h、ld、3d、5d和7d时间点(每个时间点6只).采用改良二次注血法制作脑出血模型.阿托伐他汀组在模型制作后给予阿托伐他汀灌胃(20 mg/kg,1次/d),生理盐水对照组给予等体积生理盐水.采用行为学评价进行神经功能评分,TUNEL染色法检测血肿周围细胞凋亡,免疫组织化学法检测血肿周围组织CytC表达.结果 行为学评价显示,阿托伐他汀组和生理盐水对照组神经功能评分均随着时间的推移而逐渐下降,6h、12 h、1d和3d时无显著性差异,但5 d[(0.50±0.55)分对(1.50±0.55)分；t=3.162,P=0.010]和7d[(0.17±0.41)分对(1.00±0.63)分；t=2.712,P =0.022]时阿托伐他汀组神经功能评分显著性低于生理盐水对照组.TUNEL染色法显示,生理盐水对照组与阿托伐他汀组凋亡细胞数量均先增加后减少,高峰出现在模型制作后1d时.各组间相同时间点血肿周围凋亡细胞数量均存在显著性差异(P均=0.000),且生理盐水对照组显著性多于假手术组和阿托伐他汀组(P均＜0.05),但在7d时阿托伐他汀组凋亡细胞数量与假手术组无显著性差异[(12.69±3.35)个对(9.33 ±2.07)个；P=0.148].免疫组织化学法显示,生理盐水对照组与阿托伐他汀组CytC阳性细胞数量均先增加后减少,生理盐水对照组高峰出现在模型制作后12h时[(68.19±11.93)个],而阿托伐他汀组出现在模型制作后ld时[(35.64±9.12)个].各组间相同时间点血肿周围CytC阳性细胞数量均存在显著性差异(P均=0.000),且生理盐水对照组显著性多于假手术组和阿托伐他汀组(P均＜0.05),但在7d时阿托伐他汀组CytC阳性细胞数量与假手术组无显著性差异[(16.08±3.80)个对(13.67±2.94)个；P=0.349].结论 阿托伐他汀可抑制脑出血后血肿周围神经细胞CytC释放,从而抑制CytC介导的细胞凋亡,减轻脑出血后脑神经功能缺损.
目的 探討阿託伐他汀對大鼠腦齣血後血腫週圍組織細胞凋亡和細胞色素c(Cytochrome c,CytC)錶達的影響.方法 108隻雄性Sprague-Dawley大鼠隨機分為假手術組、生理鹽水對照組和阿託伐他汀組(每組36隻),各組再分為6h、12 h、ld、3d、5d和7d時間點(每箇時間點6隻).採用改良二次註血法製作腦齣血模型.阿託伐他汀組在模型製作後給予阿託伐他汀灌胃(20 mg/kg,1次/d),生理鹽水對照組給予等體積生理鹽水.採用行為學評價進行神經功能評分,TUNEL染色法檢測血腫週圍細胞凋亡,免疫組織化學法檢測血腫週圍組織CytC錶達.結果 行為學評價顯示,阿託伐他汀組和生理鹽水對照組神經功能評分均隨著時間的推移而逐漸下降,6h、12 h、1d和3d時無顯著性差異,但5 d[(0.50±0.55)分對(1.50±0.55)分；t=3.162,P=0.010]和7d[(0.17±0.41)分對(1.00±0.63)分；t=2.712,P =0.022]時阿託伐他汀組神經功能評分顯著性低于生理鹽水對照組.TUNEL染色法顯示,生理鹽水對照組與阿託伐他汀組凋亡細胞數量均先增加後減少,高峰齣現在模型製作後1d時.各組間相同時間點血腫週圍凋亡細胞數量均存在顯著性差異(P均=0.000),且生理鹽水對照組顯著性多于假手術組和阿託伐他汀組(P均＜0.05),但在7d時阿託伐他汀組凋亡細胞數量與假手術組無顯著性差異[(12.69±3.35)箇對(9.33 ±2.07)箇；P=0.148].免疫組織化學法顯示,生理鹽水對照組與阿託伐他汀組CytC暘性細胞數量均先增加後減少,生理鹽水對照組高峰齣現在模型製作後12h時[(68.19±11.93)箇],而阿託伐他汀組齣現在模型製作後ld時[(35.64±9.12)箇].各組間相同時間點血腫週圍CytC暘性細胞數量均存在顯著性差異(P均=0.000),且生理鹽水對照組顯著性多于假手術組和阿託伐他汀組(P均＜0.05),但在7d時阿託伐他汀組CytC暘性細胞數量與假手術組無顯著性差異[(16.08±3.80)箇對(13.67±2.94)箇；P=0.349].結論 阿託伐他汀可抑製腦齣血後血腫週圍神經細胞CytC釋放,從而抑製CytC介導的細胞凋亡,減輕腦齣血後腦神經功能缺損.
목적 탐토아탁벌타정대대서뇌출혈후혈종주위조직세포조망화세포색소c(Cytochrome c,CytC)표체적영향.방법 108지웅성Sprague-Dawley대서수궤분위가수술조、생리염수대조조화아탁벌타정조(매조36지),각조재분위6h、12 h、ld、3d、5d화7d시간점(매개시간점6지).채용개량이차주혈법제작뇌출혈모형.아탁벌타정조재모형제작후급여아탁벌타정관위(20 mg/kg,1차/d),생리염수대조조급여등체적생리염수.채용행위학평개진행신경공능평분,TUNEL염색법검측혈종주위세포조망,면역조직화학법검측혈종주위조직CytC표체.결과 행위학평개현시,아탁벌타정조화생리염수대조조신경공능평분균수착시간적추이이축점하강,6h、12 h、1d화3d시무현저성차이,단5 d[(0.50±0.55)분대(1.50±0.55)분；t=3.162,P=0.010]화7d[(0.17±0.41)분대(1.00±0.63)분；t=2.712,P =0.022]시아탁벌타정조신경공능평분현저성저우생리염수대조조.TUNEL염색법현시,생리염수대조조여아탁벌타정조조망세포수량균선증가후감소,고봉출현재모형제작후1d시.각조간상동시간점혈종주위조망세포수량균존재현저성차이(P균=0.000),차생리염수대조조현저성다우가수술조화아탁벌타정조(P균＜0.05),단재7d시아탁벌타정조조망세포수량여가수술조무현저성차이[(12.69±3.35)개대(9.33 ±2.07)개；P=0.148].면역조직화학법현시,생리염수대조조여아탁벌타정조CytC양성세포수량균선증가후감소,생리염수대조조고봉출현재모형제작후12h시[(68.19±11.93)개],이아탁벌타정조출현재모형제작후ld시[(35.64±9.12)개].각조간상동시간점혈종주위CytC양성세포수량균존재현저성차이(P균=0.000),차생리염수대조조현저성다우가수술조화아탁벌타정조(P균＜0.05),단재7d시아탁벌타정조CytC양성세포수량여가수술조무현저성차이[(16.08±3.80)개대(13.67±2.94)개；P=0.349].결론 아탁벌타정가억제뇌출혈후혈종주위신경세포CytC석방,종이억제CytC개도적세포조망,감경뇌출혈후뇌신경공능결손.
Objective To investigate the effect of atorvastatin on cytochrome c (CytC) expression and neuronal apoptosis after intracerebral hemorrhage in rots.Methods A total of 108 male Sprague-Dawley rats were randomly allocated into 3 groups:sham operation group,saline control group,and atorvastatin group (n =36 each group).All the groups were redivided into 6 h,12 h,day 1,3,5 and 7 time points (n =6 at each time point).An intracerebral hemorrhage model was induced by using a modified two-step injection method.After modeling,atorvastatin was used for gavages (20 rng/kg,once a day) in the atorvastatin group.The saline control group was given the same volume of saline.Behavior evaluation was used for neurological score.TUNEL staining was used to detect apoptosis in perihematoma tissue.Immunohistochemical method was used to detect the CytC expression in perihematoma tissue.Results Behavior evaluation showed that the neurological scores decreased gradually with the passage of time in the atorvastatin group and the saline control group.There were no significant differences at 6 h,12 h,day 1 and day 3,but the neurological scores in the atorvastatin group were significantly lower than those in thc saline control group at day 5 (0.50 ± 0.55 vs.1.50 ± 0.55; t =3.162,P =0.010) and day 7 (1.00 ±0.63; t =2.712,P =0.022).TUNEL staining showed that the numbers of apoptotic cells increased first and then decreased in the saline control group and the atorvastatin group.They reached the peak at 1 hour after modeling.There were significant differences in the number of apoptotic cells in each group in perihematoma tissue at the same time point (all P =0.000),and the significance in the saline control group was more than that in the sham operation group and the atorvastatin group (all P ＜0.05),but at day 7,there was no significant difference in the number of apoptotic cells between the atorvastatin group and the sham operation group (12.69 ± 3.35 vs.9.33 ± 2.07; P =0.148).Immunohistochemical method showed that the numbers of CytC positive cells increased first and then decreased in the saline control group and the atorvastatin group,reached the peak at 12 h after modeling in te saline control group (68.19 ± 11.93) and at 1 d in the atorvastatin group (35.64 ± 9.12).There were significant differences in the numbers of CytC positive cells in perihematoma tissue at the same time point in each group (P =0.000).The numbers of CytC positive cells in the saline control group was significantly more than that in the sham operation group and the atorvastatin group (all P ＜0.05),but there was no significant difference in the numbers of CytC positive cells between the atorvastatin statin group and the sham group at day 7 (16.08 ± 3.80 vs.13.67 ± 2.94; P =0.349).Conelusions Atorvastatin may inhibit the release of CytC of nerve cells in perihematoma tissue after intracerebral hemorrhage,and thus reduce CytC-mediated apoptosis and neurological deficit after intracerebral hemorrhage.
