中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2015年
3期
347-351
,共5页
朱冰青%陈立建%章雨雯%陈满丽%张雷%顾尔伟
硃冰青%陳立建%章雨雯%陳滿麗%張雷%顧爾偉
주빙청%진립건%장우문%진만려%장뢰%고이위
糖尿病%哌啶类%内质网%应激%心肌再灌注损伤
糖尿病%哌啶類%內質網%應激%心肌再灌註損傷
당뇨병%고정류%내질망%응격%심기재관주손상
Diabetes mellitus%Piperidines%Endoplasmic reticulum%Stress%Myocardial reperfusion injury
目的 探讨内质网应激与糖尿病因素影响大鼠瑞芬太尼后处理心肌保护作用的关系.方法 健康成年雄性SD大鼠,体重250 ～ 300 g,采用腹腔注射链脲佐菌素50 mg/kg的方法制备1型糖尿病模型.取糖尿病模型制备成功的大鼠36只,采用随机数字表法,将其分为3组(n-12):假手术组(DM-S组)、心肌缺血再灌注组(DM-IR组)和瑞芬太尼后处理组(DM-R组).另取正常大鼠36只,腹腔注射柠檬酸钠缓冲液50 mg/kg作为对照.2周后,采用随机数字表法分为3组(n=12):假手术组(NDM-S组)、心肌缺血再灌注组(NDM-IR组)和瑞芬太尼后处理组(NDM-R组).采用结扎左冠状动脉前降支30 min,再灌注120 min的方法建立大鼠心肌缺血再灌注损伤模型.NDM-R组和DM-R组于再灌注前5 min经股静脉输注瑞芬太尼10 μg· kg-1 ·min-1持续10 min.于缺血前、缺血30min和再灌注120 min时记录MAP、SP和HR,计算心率收缩压乘积(RPP).于再灌注120 min时取颈动脉血样,测定血浆cTnI浓度,处死大鼠后取心脏,计算心肌梗死体积;取心尖部组织,采用Western blot法检测内质网应激相关分子葡萄糖调节蛋白78(GRP78)、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)和caspase-12的表达水平.结果 非糖尿病与糖尿病大鼠心肌缺血再灌注时MAP和RPP降低,血浆cTnI浓度升高,心肌发生梗死样改变,心肌组织GRP78、CHOP和caspase-12表达上调.瑞芬太尼后处理可抑制非糖尿病大鼠心肌缺血再灌注时心肌组织GRP78、CHOP和caspase-12的表达,升高MAP和RPP,降低血浆cTnI浓度,减小心肌梗死体积,但对糖尿病大鼠无此作用.瑞芬太尼后处理后糖尿病大鼠心肌缺血再灌注时心肌组织GRP78、CHOP和caspase-12的表达水平高于非糖尿病大鼠.结论 糖尿病因素取消大鼠瑞芬太尼后处理心肌保护作用与内质网应激水平增强有关.
目的 探討內質網應激與糖尿病因素影響大鼠瑞芬太尼後處理心肌保護作用的關繫.方法 健康成年雄性SD大鼠,體重250 ～ 300 g,採用腹腔註射鏈脲佐菌素50 mg/kg的方法製備1型糖尿病模型.取糖尿病模型製備成功的大鼠36隻,採用隨機數字錶法,將其分為3組(n-12):假手術組(DM-S組)、心肌缺血再灌註組(DM-IR組)和瑞芬太尼後處理組(DM-R組).另取正常大鼠36隻,腹腔註射檸檬痠鈉緩遲液50 mg/kg作為對照.2週後,採用隨機數字錶法分為3組(n=12):假手術組(NDM-S組)、心肌缺血再灌註組(NDM-IR組)和瑞芬太尼後處理組(NDM-R組).採用結扎左冠狀動脈前降支30 min,再灌註120 min的方法建立大鼠心肌缺血再灌註損傷模型.NDM-R組和DM-R組于再灌註前5 min經股靜脈輸註瑞芬太尼10 μg· kg-1 ·min-1持續10 min.于缺血前、缺血30min和再灌註120 min時記錄MAP、SP和HR,計算心率收縮壓乘積(RPP).于再灌註120 min時取頸動脈血樣,測定血漿cTnI濃度,處死大鼠後取心髒,計算心肌梗死體積;取心尖部組織,採用Western blot法檢測內質網應激相關分子葡萄糖調節蛋白78(GRP78)、C/EBP環燐痠腺苷反應元件結閤轉錄因子同源蛋白(CHOP)和caspase-12的錶達水平.結果 非糖尿病與糖尿病大鼠心肌缺血再灌註時MAP和RPP降低,血漿cTnI濃度升高,心肌髮生梗死樣改變,心肌組織GRP78、CHOP和caspase-12錶達上調.瑞芬太尼後處理可抑製非糖尿病大鼠心肌缺血再灌註時心肌組織GRP78、CHOP和caspase-12的錶達,升高MAP和RPP,降低血漿cTnI濃度,減小心肌梗死體積,但對糖尿病大鼠無此作用.瑞芬太尼後處理後糖尿病大鼠心肌缺血再灌註時心肌組織GRP78、CHOP和caspase-12的錶達水平高于非糖尿病大鼠.結論 糖尿病因素取消大鼠瑞芬太尼後處理心肌保護作用與內質網應激水平增彊有關.
목적 탐토내질망응격여당뇨병인소영향대서서분태니후처리심기보호작용적관계.방법 건강성년웅성SD대서,체중250 ～ 300 g,채용복강주사련뇨좌균소50 mg/kg적방법제비1형당뇨병모형.취당뇨병모형제비성공적대서36지,채용수궤수자표법,장기분위3조(n-12):가수술조(DM-S조)、심기결혈재관주조(DM-IR조)화서분태니후처리조(DM-R조).령취정상대서36지,복강주사저몽산납완충액50 mg/kg작위대조.2주후,채용수궤수자표법분위3조(n=12):가수술조(NDM-S조)、심기결혈재관주조(NDM-IR조)화서분태니후처리조(NDM-R조).채용결찰좌관상동맥전강지30 min,재관주120 min적방법건립대서심기결혈재관주손상모형.NDM-R조화DM-R조우재관주전5 min경고정맥수주서분태니10 μg· kg-1 ·min-1지속10 min.우결혈전、결혈30min화재관주120 min시기록MAP、SP화HR,계산심솔수축압승적(RPP).우재관주120 min시취경동맥혈양,측정혈장cTnI농도,처사대서후취심장,계산심기경사체적;취심첨부조직,채용Western blot법검측내질망응격상관분자포도당조절단백78(GRP78)、C/EBP배린산선감반응원건결합전록인자동원단백(CHOP)화caspase-12적표체수평.결과 비당뇨병여당뇨병대서심기결혈재관주시MAP화RPP강저,혈장cTnI농도승고,심기발생경사양개변,심기조직GRP78、CHOP화caspase-12표체상조.서분태니후처리가억제비당뇨병대서심기결혈재관주시심기조직GRP78、CHOP화caspase-12적표체,승고MAP화RPP,강저혈장cTnI농도,감소심기경사체적,단대당뇨병대서무차작용.서분태니후처리후당뇨병대서심기결혈재관주시심기조직GRP78、CHOP화caspase-12적표체수평고우비당뇨병대서.결론 당뇨병인소취소대서서분태니후처리심기보호작용여내질망응격수평증강유관.
Objective To evaluate the relationship between endoplasmic reticulum stress and diabetes mellitus (DM)-caused influence on cardioprotection induced by remifentanil postconditioning in rats.Methods Adult male Sprague-Dawley rats,weighing 250-300 g,were used in the study.A model for type 1 DM was established by intraperitoneal streptozotocin 50 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L.Thirty six rats with type 1 DM were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (DM-S group),myocardial ischemia-reperfusion (I/R) group (DM-I/R group) and remifentanil postconditioning group (DM-R group).Another 36 normal rats were exposed to single intraperitoneal injection of sodium citrate-hydrochloric acid buffer solution and served as control group.Two weeks later 36 normal rats with nondiabetes mellitus were also randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (NDM-S group),myocardial I/ R group (NDM-I/R group) and remifentanil postconditioning group (NDM-R group).Myocardial I/R was produced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.Remifentanil postconditioning was induced by 10 min infusion of remifentanil 10 μg · kg-1 · min 1 via the femoral vein starting from 5 min before reperfusion.Before ischemia and at 30 and 120 min of ischemia,MAP,SP and HR were recorded and rate-pressure product (RPP) was calculated.At 120 min of reperfusion,arterial blood samples were collected for measurement of plasma cardiac troponin I (cTnI) concentration.The animals were then sacrificed and hearts were removed for determination of myocardial infarct size (IS).The left 6 rats from each group were sacrificed at 120 min of reperfusion,the specimens from their left ventricular apex were obtained to detect the expression of endoplasmic reticulum stress marker glucose-regulated protein 78 (GRP78),C/EBP homologous protein (CHOP) and caspase-12 by Western blot.Results MAP and RPP were significantly decreased,the plasma concentration of cTnI was increased,changes of cardiac infarction were found,and the expression of GRP78,CHOP and caspase-12 was up-regulated in diabetic and nondiabetic rats.Remifentanil postconditioning could inhibit the expression of GRP78,CHOP and caspase-12,increase MAP and RPP,decrease the plasma concentration of cTnI,and reduce myocardial infarct size in nondiabetic rats,but it had no such effects in the diabetic rats.The expression of GRP78,CHOP and caspase-12 was significantly higher after remifentanil postconditioning in diabetic rats than in nondiabetic rats.Conclusion Enhanced endoplasmic reticulum stress is involved in DM-caused loss of cardioprotection induced by remifentanil postconditioning in rats.
