CAJ | 학술논문

目的评价线粒体通透性转换孔(mPTP)在舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法雄性SD大鼠60只,体重350 ～ 420 g,14～ 15周龄,采用随机数字表法,将大鼠随机分为4组(n=15):假手术组(S组)、缺血再灌注组(I/R组)、环孢菌素A组(CP组)、舒芬太尼后处理组(SP组).采用结扎左冠状动脉前降支30 min后再灌注的方法制备心肌缺血再灌注模型.于再灌注前5 min时,CP组、SP组和I/R组分别经颈静脉注射环孢菌素A 5 mg/kg、舒芬太尼1 μg/kg或等容量生理盐水.于再灌注10 min时取心脏,提取心肌细胞线粒体,应用紫外分光光度计测定mPTP活性.于平衡30 min、缺血30 min、再灌注120 min时记录MAP和HR,计算收缩压与HR乘积(RPP).于再灌注120 min时采集动脉血样3 ml,测定血浆cTnⅠ浓度,处死后取心脏,测定缺血危险区(AAR)和梗死区(IS)体积,计算IS/AAR.透射电镜下观察心肌线粒体超微结构.结果与S组比较,I/R组、CP组和SP组mPTP活性和血浆cTnⅠ浓度升高,MAP和RPP降低(P＜0.05).与I/R组比较,CP组和SP组mPTP活性、血浆cTnⅠ浓度和IS/AAR降低,CP组MAP升高(P＜0.05).与CP组比较,SP组MAP降低(P＜0.05),其余指标差异无统计学意义(P＞0.05).I/R组线粒体显著肿胀、嵴断裂甚至空泡化,CP组及SP组线粒体结构较I/R组完整,少量线粒体嵴断裂.结论舒芬太尼后处理减轻心肌缺血再灌注损伤的机制与抑制心肌细胞mPTP开放有关.
목적 평개선립체통투성전환공(mPTP)재서분태니후처리감경대서심기결혈재관주손상중적작용.방법 웅성SD대서60지,체중350 ～ 420 g,14～ 15주령,채용수궤수자표법,장대서수궤분위4조(n=15):가수술조(S조)、결혈재관주조(I/R조)、배포균소A조(CP조)、서분태니후처리조(SP조).채용결찰좌관상동맥전강지30 min후재관주적방법제비심기결혈재관주모형.우재관주전5 min시,CP조、SP조화I/R조분별경경정맥주사배포균소A 5 mg/kg、서분태니1 μg/kg혹등용량생리염수.우재관주10 min시취심장,제취심기세포선립체,응용자외분광광도계측정mPTP활성.우평형30 min、결혈30 min、재관주120 min시기록MAP화HR,계산수축압여HR승적(RPP).우재관주120 min시채집동맥혈양3 ml,측정혈장cTnⅠ농도,처사후취심장,측정결혈위험구(AAR)화경사구(IS)체적,계산IS/AAR.투사전경하관찰심기선립체초미결구.결과 여S조비교,I/R조、CP조화SP조mPTP활성화혈장cTnⅠ농도승고,MAP화RPP강저(P＜0.05).여I/R조비교,CP조화SP조mPTP활성、혈장cTnⅠ농도화IS/AAR강저,CP조MAP승고(P＜0.05).여CP조비교,SP조MAP강저(P＜0.05),기여지표차이무통계학의의(P＞0.05).I/R조선립체현저종창、척단렬심지공포화,CP조급SP조선립체결구교I/R조완정,소량선립체척단렬.결론 서분태니후처리감경심기결혈재관주손상적궤제여억제심기세포mPTP개방유관.
Objective To evaluate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in rats.Methods Sixty male Sprague-Dawley rats,aged 14-15 weeks,weighing 350-420 g,were randomly divided into 4 groups (n =15 each):sham operation group (group S),group I/R,cyclosporin A group (group CP) and sufentanil postconditioning group (group SP).Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artcry for 30 min followed by reperfusion.In groups CP and SP,cyclosporin A 5 mg/kg and sufentanil 1 μg/kg were injected via the jugular vein at 5 min before reperfusion respectively,while the equal volume of normal saline was injected in group I/R.At 10 min of reperfusion,hearts were excised,the myocardial mitochondria were immediately isolated and the activity of mPTP was measured by spectrophotometry.MAP and HR were recorded at 30 min of equilibration,at 30 min of ischemia and at 120 min of reperfusion and rate-pressure product (RPP) was calculated.Arterial blood samples were obtained at 120 min of reperfusion for determination of the plasma cardiac troponin Ⅰ (cTnⅠ) concentration.The animals were then sacrificed for determination of infarct size (IS) and area at risk (AAR),and IS/AAR was calculated.The mitochondrial ultra-structure was examined with electron microscope.Results Compared with group S,the mPTP activity and plasma cTnI concentration were significantly increased,and MAP and RPP were significantly decreased in the other three groups (P ＜ 0.05).Compared with group I/R,the mPTP activity,plasma cTnI concentration and IS/ARR were significantly decreased in groups CP and SP,and MAP was significantly increased in group CP (P ＜ 0.05).Compared with group CP,MAP was significantly decreased (P ＜ 0.05),while no significant change was found in the other indexes in group SP (P ＞0.05).Significant mitochondrial swelling,and disruption and disappearance of cristae were showed in I/R group.The mitochondrial structure was more complete in CP and SP groups than that in group I/R,and the disrupted cristae were found in a small number of mitochondria in CP and SP groups.Conclusion The mechanism by which sufentanil postconditioning reduces myocardial I/R injury is related to inhibition of mPTP opening in rats.