山东大学学报（医学版）
山東大學學報（醫學版）
산동대학학보（의학판）
JOURNAL OF SHANDONG UNIVERSITY(HEALTH SCIENCES)
2015年
5期
15-20
,共6页
李明华%王甲莉%徐峰%袁秋环%刘宝山%庞佼佼%张运%陈玉国
李明華%王甲莉%徐峰%袁鞦環%劉寶山%龐佼佼%張運%陳玉國
리명화%왕갑리%서봉%원추배%류보산%방교교%장운%진옥국
乙醛脱氢酶 2%急性高血糖%大鼠%心肌缺血%心肌再灌注损伤
乙醛脫氫酶 2%急性高血糖%大鼠%心肌缺血%心肌再灌註損傷
을철탈경매 2%급성고혈당%대서%심기결혈%심기재관주손상
Aldehyde dehydrogenase 2%Acute hyperglycemia%Rats%Myocardial ischemia%Myocardial reperfusion injury
目的：探讨乙醛脱氢酶2（ALDH2）在急性高血糖加重大鼠心肌缺血／再灌注（I／R）损伤中的活性变化及作用。方法48只雄性 Wistar 大鼠随机分为假手术组（SHAM 组）、盐水对照组（CON 组）、高糖组（HG 组）和高糖＋Alda-1干预组（HG ＋Alda-1组），每组12只。采用左冠脉前降支（LAD）结扎缺血30 min，再灌注1 h，建立大鼠心肌 I／R 模型。在建立大鼠心肌 I／R 模型同时，经颈静脉给予首负荷剂量50％葡萄糖（3 g ／kg），使大鼠血糖浓度迅速升高至20～28 mmol／L，持续微量泵入[4 mL／（kg·h）]，使大鼠血糖浓度维持在20～28 mmol／L，至再灌注结束。SHAM 组和 CON 组给予0．9％NaCl（6 mL／kg）。HG ＋Alda-1组给予 Alda-1（8．5 mg ／kg）微量泵入，至再灌注结束。再灌注结束后取心脏，采用比色法检测 ALDH2活性的变化，HE 染色观察心肌组织形态学变化，TTC 染色法检测心肌梗死面积，TUNEL 法检测心肌细胞凋亡情况。结果与 CON 组相比，HG 组在缺血期和再灌注期血糖浓度明显升高[（23．4±0．21）vs （5．8±0．21）mmol／L，P ＜0．01]。HG 组 ALDH2活性明显低于 CON 组[（69．1±5．16）％ vs （87．0±4．30）％，P ＜0．05]。HG 组心肌梗死面积明显高于 CON 组[（38．2±3．30）％ vs （26．8±2．53）％，P ＜0．05]；HG ＋Alda-1组心肌梗死面积明显低于 HG 组[（27．8±2．50）％ vs （38．2±3．30）％，P ＜0．05]。HG 组心肌细胞凋亡指数明显高于 CON 组[（16．1±0．83）％ vs （13．1±0．39）％，P ＜0．05]；HG ＋Alda-1组心肌细胞凋亡指数明显低于 HG 组[（13．6±0．51）％ vs （16．1±0．83）％，P ＜0．05]。结论急性高血糖可加重 I／R 大鼠的心肌梗死面积及心肌细胞凋亡，使心肌 ALDH2的活性降低；增强 ALDH2活性可显著减少急性高血糖大鼠 I／R 后的心肌梗死面积及心肌细胞凋亡。
目的：探討乙醛脫氫酶2（ALDH2）在急性高血糖加重大鼠心肌缺血／再灌註（I／R）損傷中的活性變化及作用。方法48隻雄性 Wistar 大鼠隨機分為假手術組（SHAM 組）、鹽水對照組（CON 組）、高糖組（HG 組）和高糖＋Alda-1榦預組（HG ＋Alda-1組），每組12隻。採用左冠脈前降支（LAD）結扎缺血30 min，再灌註1 h，建立大鼠心肌 I／R 模型。在建立大鼠心肌 I／R 模型同時，經頸靜脈給予首負荷劑量50％葡萄糖（3 g ／kg），使大鼠血糖濃度迅速升高至20～28 mmol／L，持續微量泵入[4 mL／（kg·h）]，使大鼠血糖濃度維持在20～28 mmol／L，至再灌註結束。SHAM 組和 CON 組給予0．9％NaCl（6 mL／kg）。HG ＋Alda-1組給予 Alda-1（8．5 mg ／kg）微量泵入，至再灌註結束。再灌註結束後取心髒，採用比色法檢測 ALDH2活性的變化，HE 染色觀察心肌組織形態學變化，TTC 染色法檢測心肌梗死麵積，TUNEL 法檢測心肌細胞凋亡情況。結果與 CON 組相比，HG 組在缺血期和再灌註期血糖濃度明顯升高[（23．4±0．21）vs （5．8±0．21）mmol／L，P ＜0．01]。HG 組 ALDH2活性明顯低于 CON 組[（69．1±5．16）％ vs （87．0±4．30）％，P ＜0．05]。HG 組心肌梗死麵積明顯高于 CON 組[（38．2±3．30）％ vs （26．8±2．53）％，P ＜0．05]；HG ＋Alda-1組心肌梗死麵積明顯低于 HG 組[（27．8±2．50）％ vs （38．2±3．30）％，P ＜0．05]。HG 組心肌細胞凋亡指數明顯高于 CON 組[（16．1±0．83）％ vs （13．1±0．39）％，P ＜0．05]；HG ＋Alda-1組心肌細胞凋亡指數明顯低于 HG 組[（13．6±0．51）％ vs （16．1±0．83）％，P ＜0．05]。結論急性高血糖可加重 I／R 大鼠的心肌梗死麵積及心肌細胞凋亡，使心肌 ALDH2的活性降低；增彊 ALDH2活性可顯著減少急性高血糖大鼠 I／R 後的心肌梗死麵積及心肌細胞凋亡。
목적：탐토을철탈경매2（ALDH2）재급성고혈당가중대서심기결혈／재관주（I／R）손상중적활성변화급작용。방법48지웅성 Wistar 대서수궤분위가수술조（SHAM 조）、염수대조조（CON 조）、고당조（HG 조）화고당＋Alda-1간예조（HG ＋Alda-1조），매조12지。채용좌관맥전강지（LAD）결찰결혈30 min，재관주1 h，건립대서심기 I／R 모형。재건립대서심기 I／R 모형동시，경경정맥급여수부하제량50％포도당（3 g ／kg），사대서혈당농도신속승고지20～28 mmol／L，지속미량빙입[4 mL／（kg·h）]，사대서혈당농도유지재20～28 mmol／L，지재관주결속。SHAM 조화 CON 조급여0．9％NaCl（6 mL／kg）。HG ＋Alda-1조급여 Alda-1（8．5 mg ／kg）미량빙입，지재관주결속。재관주결속후취심장，채용비색법검측 ALDH2활성적변화，HE 염색관찰심기조직형태학변화，TTC 염색법검측심기경사면적，TUNEL 법검측심기세포조망정황。결과여 CON 조상비，HG 조재결혈기화재관주기혈당농도명현승고[（23．4±0．21）vs （5．8±0．21）mmol／L，P ＜0．01]。HG 조 ALDH2활성명현저우 CON 조[（69．1±5．16）％ vs （87．0±4．30）％，P ＜0．05]。HG 조심기경사면적명현고우 CON 조[（38．2±3．30）％ vs （26．8±2．53）％，P ＜0．05]；HG ＋Alda-1조심기경사면적명현저우 HG 조[（27．8±2．50）％ vs （38．2±3．30）％，P ＜0．05]。HG 조심기세포조망지수명현고우 CON 조[（16．1±0．83）％ vs （13．1±0．39）％，P ＜0．05]；HG ＋Alda-1조심기세포조망지수명현저우 HG 조[（13．6±0．51）％ vs （16．1±0．83）％，P ＜0．05]。결론급성고혈당가가중 I／R 대서적심기경사면적급심기세포조망，사심기 ALDH2적활성강저；증강 ALDH2활성가현저감소급성고혈당대서 I／R 후적심기경사면적급심기세포조망。
Objective To investigate the activity changes and actions of aldehyde dehydrogenase 2 (ALDH2)in myocardial ischemia/reperfusion injury exacerbated by acute hyperglycemia.Methods A total of 48 male Wistar rats were randomly divided into 4 groups:sham operation (SHAM)group,normal saline control (CON)group,high blood glucose (HG)group,and HG with Alda-1 administration (HG +Alda-1)group,with 12 animals in each group. The left anterior descending artery (LAD)was occluded for 30 minutes followed by 1 hour reperfusion to establish my-ocardial ischemia-reperfusion rat models.Acute hyperglycemia rat models were established via jugular vein injection of 50% glucose (3 g /kg)during the ischemia period.Blood glucose levels were maintained at 20-28 mmol/L throughout the experiment by administration of glucose with trace pumping[4 mL/(kg·h)]during ischemia and reperfusion peri-od.The rats in CON group and HG +Alda-1 group were given normal saline (6 mL/kg).The rats in HG +Alda-1 group were given Alda-1 (8.5 mg /kg)with trace pumping during ischemia and reperfusion.After reperfusion,ALDH2 activity of heart was detected with colorimetric method,changes of myocardial tissue morphology were observed with HE staining,myocardial infarction size was determined with TTC staining,and myocardial cell apoptosis was tested with TUNEL method.Results Blood glucose level was significantly increased in HG group compared with that of CON group [(23.4 ±0.21 )vs (5.8 ±0.21 )mmol/L,P <0.01 ].Compared with CON group,the activity of ALDH2 in HG group was markedly decreased [(69.1 ±5.16)% vs (87.0 ±4.30)%,P <0.05].Myocardial infarct size of HG group was remarkably increased compared with the CON group [(38.2 ±3.30)% vs (26.8 ±2.53)%, P <0.05].Compared with HG group,myocardial infarct size of HG +Alda-1 group was notedly decreased [(27.8 ± 2.50)% vs (38.2 ±3.30)%,P <0.05].Myocardial apoptosis index of HG group was significantly higher than that of CON group [(16.1 ±0.83)% vs (13.1 ±0.39)%,P <0.05].Compared with HG group,myocardial apoptosis of HG +Alda-1 group was significantly reduced [(13.6 ±0.51)% vs (16.1 ±0.83)%,P <0.05].Conclusion Acute hyperglycemia significantly increases myocardial infarct size and myocardial apoptosis induced by myocardial ischemia-reperfusion injury and reduced ALDH2 activity,while enhanced ALDH2 activity can markedly decrease myo-cardial infarct size and myocardial apoptosis during ischemia-reperfusion injury in acute hyperglycemia rats.
