背景:在临床实践中异丙酚可以收缩脑血管,降低脑血流量,减少脑代谢耗氧量,从而达到降低颅压的目的.实验证实异丙酚对活性氧损伤的内皮细胞具有良好的保护作用,对实验性大鼠脑缺血的神经损害有保护作用.目的:观察异丙酚对大鼠脑缺血再灌注损伤的保护作用及其机制.设计:随机对照实验.单位:西安交通大学医学院第二附属医院麻醉科.材料:实验于~2004年西安交通大学医学院药理实验室完成.选取健康清洁级SD雄性大鼠40只,鼠龄三四个月,体质量200～300g.随机分为模型组、对照组、尼莫地平组及异丙酚组,每组10只.方法:分别在大鼠腹腔内注射氯胺酮及异丙酚,待其翻正反射消失后,分离并结扎颈外动脉,对照组仅将尼龙线放在颈外动脉残端处,但不结扎.模型组:在缺血前10min腹腔注入生理盐水10mL;对照组:在术毕后腹腔注入生理盐水10 mL;尼莫地平组:在缺血前10min腹腔注入10g/L尼莫地平1 mg/kg;异丙酚组:在缺血前10 min腹腔注入10g/L异丙酚110 mg/kg.除对照组外其余各组缺血3 h再灌注3 h,眼眶取血,开颅取脑,观察麻醉剂量异丙酚对脑缺血再灌注损伤的保护作用.主要观察指标:大鼠脑梗死范围,脑组织含水量,血清乳酸脱氧酶、肌酸激酶,脑组织超氧化物歧化酶活性,丙二醛含量,钙离子含量,电镜下脑细胞超微结构.结果:①异丙酚组梗死范围明显小于模型组[(10.45±3.65,19.68±4.03)%,(t=3.493,P＜0.01)].②异丙酚组肌酸激酶含量明显低于模型组[(471±200,1 930±917)IU/L(t=3.493,P＜0.01)];乳酸脱氢酶含量为(8240±2580)U/L,与模型组[(15 470±2680)U/L]比较差异有显著性意义(t=3.441,P＜0.01);异丙酚组脑组织含水量明显低于模型组[(78.2±2.4,82.9±2.9)%,(t=3.321,P＜0.01)].③异丙酚组大鼠死亡率为13.6%,与模型组47.6%比较有显著性差异(t=6.21,P＜0.05).④异丙酚组超氧化物歧化酶活性为(1690±780)U/g,与模型组(830±110)U/g比较差异有显著性意义(t=3.420,P＜0.01);丙二醛含量明显低于模型组[(0.058±0.014,0.115±0.047)μmol/g,(t=3.36,P＜0.01)].结论:麻醉剂量异丙酚对大鼠局灶性脑缺血再灌注损伤有保护作用,其机制与抑制钙离子超载和抑制脂质过氧化反应有关.
揹景:在臨床實踐中異丙酚可以收縮腦血管,降低腦血流量,減少腦代謝耗氧量,從而達到降低顱壓的目的.實驗證實異丙酚對活性氧損傷的內皮細胞具有良好的保護作用,對實驗性大鼠腦缺血的神經損害有保護作用.目的:觀察異丙酚對大鼠腦缺血再灌註損傷的保護作用及其機製.設計:隨機對照實驗.單位:西安交通大學醫學院第二附屬醫院痳醉科.材料:實驗于~2004年西安交通大學醫學院藥理實驗室完成.選取健康清潔級SD雄性大鼠40隻,鼠齡三四箇月,體質量200～300g.隨機分為模型組、對照組、尼莫地平組及異丙酚組,每組10隻.方法:分彆在大鼠腹腔內註射氯胺酮及異丙酚,待其翻正反射消失後,分離併結扎頸外動脈,對照組僅將尼龍線放在頸外動脈殘耑處,但不結扎.模型組:在缺血前10min腹腔註入生理鹽水10mL;對照組:在術畢後腹腔註入生理鹽水10 mL;尼莫地平組:在缺血前10min腹腔註入10g/L尼莫地平1 mg/kg;異丙酚組:在缺血前10 min腹腔註入10g/L異丙酚110 mg/kg.除對照組外其餘各組缺血3 h再灌註3 h,眼眶取血,開顱取腦,觀察痳醉劑量異丙酚對腦缺血再灌註損傷的保護作用.主要觀察指標:大鼠腦梗死範圍,腦組織含水量,血清乳痠脫氧酶、肌痠激酶,腦組織超氧化物歧化酶活性,丙二醛含量,鈣離子含量,電鏡下腦細胞超微結構.結果:①異丙酚組梗死範圍明顯小于模型組[(10.45±3.65,19.68±4.03)%,(t=3.493,P＜0.01)].②異丙酚組肌痠激酶含量明顯低于模型組[(471±200,1 930±917)IU/L(t=3.493,P＜0.01)];乳痠脫氫酶含量為(8240±2580)U/L,與模型組[(15 470±2680)U/L]比較差異有顯著性意義(t=3.441,P＜0.01);異丙酚組腦組織含水量明顯低于模型組[(78.2±2.4,82.9±2.9)%,(t=3.321,P＜0.01)].③異丙酚組大鼠死亡率為13.6%,與模型組47.6%比較有顯著性差異(t=6.21,P＜0.05).④異丙酚組超氧化物歧化酶活性為(1690±780)U/g,與模型組(830±110)U/g比較差異有顯著性意義(t=3.420,P＜0.01);丙二醛含量明顯低于模型組[(0.058±0.014,0.115±0.047)μmol/g,(t=3.36,P＜0.01)].結論:痳醉劑量異丙酚對大鼠跼竈性腦缺血再灌註損傷有保護作用,其機製與抑製鈣離子超載和抑製脂質過氧化反應有關.
배경:재림상실천중이병분가이수축뇌혈관,강저뇌혈류량,감소뇌대사모양량,종이체도강저로압적목적.실험증실이병분대활성양손상적내피세포구유량호적보호작용,대실험성대서뇌결혈적신경손해유보호작용.목적:관찰이병분대대서뇌결혈재관주손상적보호작용급기궤제.설계:수궤대조실험.단위:서안교통대학의학원제이부속의원마취과.재료:실험우~2004년서안교통대학의학원약리실험실완성.선취건강청길급SD웅성대서40지,서령삼사개월,체질량200～300g.수궤분위모형조、대조조、니막지평조급이병분조,매조10지.방법:분별재대서복강내주사록알동급이병분,대기번정반사소실후,분리병결찰경외동맥,대조조부장니룡선방재경외동맥잔단처,단불결찰.모형조:재결혈전10min복강주입생리염수10mL;대조조:재술필후복강주입생리염수10 mL;니막지평조:재결혈전10min복강주입10g/L니막지평1 mg/kg;이병분조:재결혈전10 min복강주입10g/L이병분110 mg/kg.제대조조외기여각조결혈3 h재관주3 h,안광취혈,개로취뇌,관찰마취제량이병분대뇌결혈재관주손상적보호작용.주요관찰지표:대서뇌경사범위,뇌조직함수량,혈청유산탈양매、기산격매,뇌조직초양화물기화매활성,병이철함량,개리자함량,전경하뇌세포초미결구.결과:①이병분조경사범위명현소우모형조[(10.45±3.65,19.68±4.03)%,(t=3.493,P＜0.01)].②이병분조기산격매함량명현저우모형조[(471±200,1 930±917)IU/L(t=3.493,P＜0.01)];유산탈경매함량위(8240±2580)U/L,여모형조[(15 470±2680)U/L]비교차이유현저성의의(t=3.441,P＜0.01);이병분조뇌조직함수량명현저우모형조[(78.2±2.4,82.9±2.9)%,(t=3.321,P＜0.01)].③이병분조대서사망솔위13.6%,여모형조47.6%비교유현저성차이(t=6.21,P＜0.05).④이병분조초양화물기화매활성위(1690±780)U/g,여모형조(830±110)U/g비교차이유현저성의의(t=3.420,P＜0.01);병이철함량명현저우모형조[(0.058±0.014,0.115±0.047)μmol/g,(t=3.36,P＜0.01)].결론:마취제량이병분대대서국조성뇌결혈재관주손상유보호작용,기궤제여억제개리자초재화억제지질과양화반응유관.
BACKGROUND: In clinical, propofol can contract cerebral vessels, decrease cerebral blood flow, decrease brain metabolic oxygen consumption,which can decrease pressure in brain. Studies prove that propofol can protect endothelial cell that may be injuried by active oxygen injury and also decrease nerves injury of experimental rats with cerebral ischemia.OBJECTIVE: To investigate the protective effects of propofol on cerebral ischemia-reperfusion injury in rat and its mechanism.DESIGN: Randomized and controlled study.SETTING:Anesthesiological Department of the Second Affiliated Hospital of Xi'an Jiaotong University.PARTICIPANTS: The experiment was conducted at Pharmacological Laboratory of Medical College of Xi' an Jiaotong University in 2004. Totally 40 healthy male SD rats, aged 3-4 months, weighting 200-300 g, were divided randomly into four groups: Model group, control group, nimodipine group and propofol group, with 10 in each group.METHODS: The rats were anesthetized by intraperitoneal methods with ketamine and propofol separately. When righting reflex was abolished, external carotid artery was separated and ligated. A nylon thread was put at the stump site of external carotid artery without ligation. Model group: 10 mL normal saline was injected into intraperitone in 10 minutes before ischemia.Control group: 10 mL normal saline was injected into intraperitone at the end of operation. Nimodipine group: 10 g/L nimodipine (1 mg/kg) was injected into intraperitone in10 minutes before ischemia. Propofol group: 10 g/L propofol (110 mg/Kg) was injected into intraperitone in 10 minutes before ischemia. When ischemia was lasted for 3 hours, nylon thread was with drawed for reperfusion. When reperfusion was lasted for 3 hours, blood samples were obtained from orbit. Skulls were opened and brains were removed.Effect of propofol on cerebral ischemia-reperfusion injury was observed.MAIN OUTCOME MEASURES: Infarction area, cerebral water content,serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, brain superoxide dismutase (SOD) activity, malondialdehyde (MDA) and Ca2+levels were measured. Ultrastructure of brain tissue was examined under electron microscope.RESULTS: ①Infarct area in propofol group was significantly smaller than that in model group [(10.45±3.65, 19.68±4.03)%, (t=3.493,P ＜ 0.01)]. ② CK level was lower in propofol group than that in model group [(471±200,1 930±917) IU/L, (t=3.493, P ＜ 0.01)]; and LDH level in propofol group [(8 240±2 580) U/L] was significantly different from that in model group [(15 470±2 680) U/L, (t=3.441, P ＜ 0.01)]; And water content in brain tissue was lower in propofol group than that in model group [(78.2±2.4,82.9±2.9)%, (t=3.321, P ＜ 0.01)]. ③ The death rate of rats was 13.6%in propofol group, and 47.6% in model group, the former was decreased obviously as compared with the latter, and the difference was significant (t=6.21,P ＜ 0.05). ④ SOD activity was (1 690±780) U/g in propofol group and (830±110) U/g in model group, the difference was significant (t=3.420, P ＜ 0.01); but MDA content was obviously lower in propofol group than that in model group [(0.058±0.014, 0.115±0.047) μmol/g, (t=3.336, P ＜ 0.01)].CONCLUSION: Propofol has protective effect on cerebral ischemia-reper fusion injury in rats, and the mechanism is related with inhibition of Ca2+overloading and lipid peroxidation.
