丙泊酚对大鼠肾缺血再灌注损伤细胞凋亡信号通路的影响

丙泊酚对大鼠肾缺血再灌注损伤细胞凋亡信号通路的影响李锦;王莉莉;李树人
【期刊名称】《中国组织工程研究》
【年(卷),期】2009(013)031
【摘要】BACKGROUND:Renal ischemia/reperfusion during renal transplant surgery induces the process of apoptosis signaling pathways.Propofol possibly protects kidney from renal ischemia/reperfusion injury.So it is important to investigate propofol's mechanism underlying
apoptosis.OBJECTIVE:To investigate the effects of propofol on apoptosis signaling pathways in a rat model of renal ischemia/reperfusion injury and the possible mechanism of action.DESIGN,TIME AND SETTING:An animal experiment,cell morphology observation was performed at the laboratory of the Department of Urinary Surgery,Beijing Friendship Hospital between 2004 and 2005.MATERIALS:A total of 99 male adult outbred Sprague Dawley rats were included in this study.Rabbit anti-rat Bcl-2,Bax,caspase 3,and cytochrome C were produced in Wuhan Boster Bioengineering Co.,Ltd.,China.METHODS:Rats were randomly divided into three groups:control(n = 26),ischemia/reperfusion(n = 35),and
ischemia/reperfusion+propofol(n = 38).Rat model of renal
ischemia/reperfusion injury was established in each group as
follows.Following single intravenous transfusion of 5 mL/kg ringer lactate solution,the right kidney was excised through a median abdominal
incision.The left renal pedicle was occluded for 45 minutes using an atraumatic vascular clamp,followed by reperfusion and full-layer suture.At 0,3,12,24,and 72 hours after reperfusion,the left kidney was excised,and simultaneously,rat was sacrificed through bloodletting.In the
ischemia/reperfusion+propofol group,propofol(1 mg/kg per minute)was administered from 15 minutes prior to ischemia to 30 minutes after reperfusion,for a total of 75 minutes.In the control and
ischemia/reperfusion groups,rats were administered the same amount of ringer lactate solution.MAIN OUTCOME MEASURES:Morphological changes of injured kidney and expression of apoptosis-related protein Bcl-2,Bax,caspase 3 and cytochrome C.RESULTS:Renal ischemia/reperfusion-caused kidney damages could be observed through an optical microscope,and proximal convoluted tubule was severest,followed by distal convoluted and collecting duct,and lastly renal
glomerulus.Immunohistochemistry results demonstrated that compared with the control group,Bax,caspase 3,and cytochrome C expression was increased,but no obvious change in Bcl-2 expression was observed in the ischemia/reperfusion group;compared with the control group,Bax,caspase 3 and cytochrome C expression was significantly decreased,but Bcl-2 expression was significantly increased in the
ischemia/reperfusion+propofol group(P＜0.05).CONCLUSION:Propofol is likely to exhibit protective effects on cellular apoptosis caused by renal ischemia/reperfusion.Propofol inhibits pro-apoptotic protein Bax,caspase 3 and cytochrome C expression but does not produce effects on Bcl-2
expression.The underlying mechanism correlates with apoptosis signaling pathways in mitochondrion.%背景:肾移植中肾缺血再灌注损伤能引发凋亡程序的执行,丙泊酚可能的肾保护作用及其与细胞凋亡通路间的关系,有助于探讨丙泊酚的作用机制.目的:探讨丙泊酚对大鼠肾缺血再灌注损伤细胞凋亡通路的影响及可能的作用机制.设计,时间及地点:动物实验,细胞形态学观察,于2004/2005在北京友谊医院泌尿外科研究所实验室共同设计和完成.材料:选取封闭群SD成年雄性大鼠99只.兔抗鼠Bcl-2、Bax、caspase3、cytochrome C均为武汉博士德生物工程有限公司产品.方法:将动物随机分为对照组26只、缺血再灌注组35只、缺血再灌注+丙泊酚组38只.建立大鼠肾缺血再灌注损伤模型,术前单次静脉缓慢输注乳酸林格液5 mL/kg,逐层正中切口开骏,切除右肾,用无创血管夹夹闭左侧肾蒂,缺血时间45 min,松夹再灌注后全层缝合腹壁,取再灌注0,3,12,24,72 h左侧肾脏,取肾同时采血处死动物.缺血再灌注+丙泊酚组在缺血前15 min用药,丙泊酚1 mg/(kg·min)直至再灌注后30 min,共用药75 min.对照组和缺血再灌注组以乳酸林格液等量输注.主要观察指标:观察损伤肾的形态学改变,用免疫组织化学观察细胞凋亡相关蛋白Bcl-2、Bax、caspase 3和细胞色素C的表达情况.结果:光镜可观察到肾缺血再灌注引起的肾损害,程度依次为近曲小管、远曲小管、集合管、肾小球;免疫组化图像分析观察到缺血再灌注组与对照组相比,Bax、caspase 3,细胞色素C表达增
加,Bcl-2表达未见明显变化;缺血再灌注+丙泊酚组与对照组比较,前者Bax、caspase 3和细胞色素C表达下降,Bcl-2表达增高(P＜0.05).结论:丙泊酚对肾缺血再灌注损伤引起的细胞凋亡可能具有保护作用,可能机制是抑制促凋亡蛋白Bax、caspase 3和细胞色素C的表达,对Bcl-2的表达无影响,与细胞凋亡的线粒体通路途径有关.
【总页数】5页(P6013-6017)
【作者】李锦;王莉莉;李树人
【作者单位】首都医科大学北京天坛医院麻醉科,北京市,100050;首都医科大学北
京天坛医院麻醉科,北京市,100050;北京友谊医院麻醉科,北京市,100050
【正文语种】中文
【中图分类】R318
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