Effects of propofol on apoptosis signaling pathways in a rat model of renal ischemia/reperfusion injury
10.3969/j.issn.1673-8225.2009.31.002
- VernacularTitle: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
- Author:
Jin LI
;
Lili WANG
;
Shuren LI
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2009;13(31):6013-6017
- CountryChina
- Language:Chinese
-
Abstract:
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.