羟考酮预给药对大鼠肾缺血-再灌注损伤的影响
|
摘要
目的评价羟考酮预给药对大鼠肾缺血-再灌注损伤的影响。方法健康成年雄性SD大鼠30只,采用随机数字表法,将其分为三组(n=10),假手术组(S组):仅切除右肾、分离左侧肾动脉、肾静脉和输尿管;缺血-再灌注组(IR组):切除右侧肾脏,夹闭左侧肾动脉和肾静脉45min恢复灌注2h;羟考酮预给药+缺血-再灌注组(O组):缺血-再灌注前5min静脉注射羟考酮2mg/kg。于再灌注2h时经腹主动脉采集动脉血样,血清尿素氮(BUN)浓度采用脲酶法测定,血清肌酐(Cr)浓度采用速率法测定。处死大鼠,取部分左肾组织,超氧化物歧化酶(SOD)活性采用黄嘌呤氧化酶法测定,丙二醛(MDA)含量采用硫代巴比妥酸法测定。采用Western blot检测肾组织中B细胞淋巴瘤/白血病-2(bcl-2)、B细胞淋巴瘤/白血病-2相关x蛋白(bax)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白表达。结果与S组比较,IR组和O组血清BUN和Cr的浓度明显升高(P<0.05),肾组织MDA的含量明显升高,SOD活性明显降低(P<0.05),肾组织bax、Caspase-3蛋白表达明显升高(P<0.05),而bcl-2蛋白表达明显降低(P<0.05)。与IR组比较,O组血清BUN和Cr的浓度明显降低(P<0.05),肾组织MDA的含量明显降低,SOD活性明显升高(P<0.05)肾组织bax、Caspase-3蛋白表达明显降低(P<0.05),而bcl-2蛋白表达明显升高(P<0.05)。结论羟考酮预给药可减轻大鼠肾缺血-再灌注损伤,其机制可能与其抑制肾组织氧化应激反应和细胞凋亡有关。
Objective To evaluate the effects of oxycodone pretreatment on renal ischemiareperfusion(IR)injury in rats.Methods Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups(n=10 each)using a random number table:sham operation group(group S),group IR,and oxycodone pretreatment+IR group(group O).After removing the right kidney in rats,the renal I/R was built by occlusion of the left renal artery and vein for 45 min with a traumatic microclips followed by 2 hreperfusion in I/R and O group.In group S,the right kidney was performed and the left renal artery,vein and ureter were isolated without occluding blood flow.In group O,oxycodone 2 mg/kg were infused intravenously 5 min before onset of ischemia.At 2 hof reperfusion,blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen(BUN)and creatinine(Cr).After blood sampling,the rats were sacrificed,and the left kidney were removed for determination of malondialdehyde(MDA)content(by thiobarbituric acid method)and superoxide dismutase(SOD)activity(using xan-thine oxidase method).The expression levels of B-cell lymphoma-2(bcl-2),bcl-2 Assaciated X protein(bax)and cycteinyl aspirate-specific protease-3(Caspase-3)protein were detected by Western blotting,respectively.Results Compared with group S,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly increased,the content of bcl-2 and SOD activity in renal tissues were significantly decreased in the other two groups(P<0.05).Compared with group IR,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly decreased,the content of bcl-2 and SOD activity in renal tissues were significantly increased in group O(P<0.05).Conclusion Oxycodone can alleviate renal I/R injury in rats,and the mechanism is related to inhibition of oxidative stress response and cell apoptosis.
Objective To evaluate the effects of oxycodone pretreatment on renal ischemiareperfusion(IR)injury in rats.Methods Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups(n=10 each)using a random number table:sham operation group(group S),group IR,and oxycodone pretreatment+IR group(group O).After removing the right kidney in rats,the renal I/R was built by occlusion of the left renal artery and vein for 45 min with a traumatic microclips followed by 2 hreperfusion in I/R and O group.In group S,the right kidney was performed and the left renal artery,vein and ureter were isolated without occluding blood flow.In group O,oxycodone 2 mg/kg were infused intravenously 5 min before onset of ischemia.At 2 hof reperfusion,blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen(BUN)and creatinine(Cr).After blood sampling,the rats were sacrificed,and the left kidney were removed for determination of malondialdehyde(MDA)content(by thiobarbituric acid method)and superoxide dismutase(SOD)activity(using xan-thine oxidase method).The expression levels of B-cell lymphoma-2(bcl-2),bcl-2 Assaciated X protein(bax)and cycteinyl aspirate-specific protease-3(Caspase-3)protein were detected by Western blotting,respectively.Results Compared with group S,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly increased,the content of bcl-2 and SOD activity in renal tissues were significantly decreased in the other two groups(P<0.05).Compared with group IR,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly decreased,the content of bcl-2 and SOD activity in renal tissues were significantly increased in group O(P<0.05).Conclusion Oxycodone can alleviate renal I/R injury in rats,and the mechanism is related to inhibition of oxidative stress response and cell apoptosis.
引文
[1]叶元梅,冷玉芳,杨佩宁,等.羟考酮预先给药对大鼠心肌缺血再灌注损伤的影响及其与P13K/Akt信号通路的关系.中华麻醉学杂志,2016,36(8):946-949.
[2]Basile DP,Donohoe D,Cao X,et al.Resistance to ischemic acute renal failure in the Brown Norway rat:a new model to study cytoprotection.Kidney Int,2004,65(6):2201-2211.
[3]陈刘芳,靖国庆,杨建国,等.不同剂量羟考酮对大鼠肾缺血再灌注损伤的影响.中华麻醉学杂志,2015,35(10):1277-1280.
[4]周大春,马晓旭,谢俊然,等.羟乙基淀粉(130/0.4)对大鼠肾脏缺血再灌注损伤的保护.中华医学杂志,2007,87(45):3224-3227.
[5]Alge JL,Arthur JM.Biomarkers of AKI:a review of mechanistic relevance and potential therapeutic implications.Clin J Am Soc Nephrol,2015,10(1):147-155.
[6]姜俊,滕杰,丁小强.急性肾损伤患者远期预后的研究进展.中华医学杂志,2014,94(8):635-637.
[7]Sithisarn T,Bada HS,Charnigo RJ,et al.Effects of pefinatal oxycodone exposure on the cardiovascular response to acute stress in male rats at weaning and in young adulthood.Front Physiol,2013,4:85.
[8]HE F,Xu BL,Chen C,et al.Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating P13K/Akt/eNOS signaling pathway.Acta Pharmacol Sin,2016,37(6):763-771.
[9]Fang J,Hu F,Ke D,et al.N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through P13K/Akt pathway in mice.Basic Res Cardiol,2016,111(3):32.
[10]张引,金世云,何淑芳,等.JNK信号通路和p38MAPK信号通路在吗啡预处理减轻心力衰竭大鼠心肌缺血再灌注损伤中的作用.中华麻醉学杂志,2016,36(2):219-222.
[11]Stoops WW,Hatton KW,Lofwall MR,et al.Intravenous oxycodone,hydrocodone,and morphine in recreational opioid users:abuse potential and relative potencies.Psychopharmacology(Berl),2010,212(2):193-203.
[12]王英,谢平,张琳,等.PI3K/Akt/GSK-3β信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用:离体实验.中华麻醉学杂志,2014,34(10):1237-1240.
[13]刘春伟,丛洪良,于雪芳,等.PI3K-Akt、mito-KATP通道及mPTP在阿托伐他汀后处理减轻大鼠心肌缺血再灌注损伤中的作用.天津医药,2015,43(1):46-50.
[14]Ahmad A,Olah G,Szezesny B,et al.AP39,A mitoehondrially targeted hydrogen sulfide donor,exerts protective effects in renal epithelial cells subjected to oxidative stress in vitro and in acute renal injury in vivo.Shock,2016,45(1):88-97.
[15]Hatcher HC,Tesfay L,Torti SV,et al.Cytoproteetive effect of ferritin H in renal isehemia reperfusion injury.PLoS One,2015,10(9):e0138505.
[16]Hanci V,Erol B,Bektas S,et al.Effect of dexmedetomidine on testicular torsion/detorsion damage in rats.Urol Int,2010,84(1):105-111.
[17]Groban L,Vernon JC,Butterworth J.Intrathecal morphine reduces infarct size in a rat model of ischemia-reperfnsion injury.Anesth Analg,2014,98(4):903-909.
[18]熊颖芬,金小雪,孟叶,等.阿片受体在瑞芬太尼减轻大鼠肾脏缺血再灌注损伤中的作用.中华麻醉学杂志,2012,32(7):877-879
[19]Huber TB,Edelstein CL,Hartleben B,et al.Emerging role of autophagy in kidney function,diseases and aging.Autophagy,2012,8(7):1009-1031.
[20]刘振臻,冷玉芳,李轩杰,等.羟考酮预先给药对大鼠肾缺血再灌注时自噬的影响.中华麻醉学杂志,2017,37(3):379-381.
[2]Basile DP,Donohoe D,Cao X,et al.Resistance to ischemic acute renal failure in the Brown Norway rat:a new model to study cytoprotection.Kidney Int,2004,65(6):2201-2211.
[3]陈刘芳,靖国庆,杨建国,等.不同剂量羟考酮对大鼠肾缺血再灌注损伤的影响.中华麻醉学杂志,2015,35(10):1277-1280.
[4]周大春,马晓旭,谢俊然,等.羟乙基淀粉(130/0.4)对大鼠肾脏缺血再灌注损伤的保护.中华医学杂志,2007,87(45):3224-3227.
[5]Alge JL,Arthur JM.Biomarkers of AKI:a review of mechanistic relevance and potential therapeutic implications.Clin J Am Soc Nephrol,2015,10(1):147-155.
[6]姜俊,滕杰,丁小强.急性肾损伤患者远期预后的研究进展.中华医学杂志,2014,94(8):635-637.
[7]Sithisarn T,Bada HS,Charnigo RJ,et al.Effects of pefinatal oxycodone exposure on the cardiovascular response to acute stress in male rats at weaning and in young adulthood.Front Physiol,2013,4:85.
[8]HE F,Xu BL,Chen C,et al.Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating P13K/Akt/eNOS signaling pathway.Acta Pharmacol Sin,2016,37(6):763-771.
[9]Fang J,Hu F,Ke D,et al.N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through P13K/Akt pathway in mice.Basic Res Cardiol,2016,111(3):32.
[10]张引,金世云,何淑芳,等.JNK信号通路和p38MAPK信号通路在吗啡预处理减轻心力衰竭大鼠心肌缺血再灌注损伤中的作用.中华麻醉学杂志,2016,36(2):219-222.
[11]Stoops WW,Hatton KW,Lofwall MR,et al.Intravenous oxycodone,hydrocodone,and morphine in recreational opioid users:abuse potential and relative potencies.Psychopharmacology(Berl),2010,212(2):193-203.
[12]王英,谢平,张琳,等.PI3K/Akt/GSK-3β信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用:离体实验.中华麻醉学杂志,2014,34(10):1237-1240.
[13]刘春伟,丛洪良,于雪芳,等.PI3K-Akt、mito-KATP通道及mPTP在阿托伐他汀后处理减轻大鼠心肌缺血再灌注损伤中的作用.天津医药,2015,43(1):46-50.
[14]Ahmad A,Olah G,Szezesny B,et al.AP39,A mitoehondrially targeted hydrogen sulfide donor,exerts protective effects in renal epithelial cells subjected to oxidative stress in vitro and in acute renal injury in vivo.Shock,2016,45(1):88-97.
[15]Hatcher HC,Tesfay L,Torti SV,et al.Cytoproteetive effect of ferritin H in renal isehemia reperfusion injury.PLoS One,2015,10(9):e0138505.
[16]Hanci V,Erol B,Bektas S,et al.Effect of dexmedetomidine on testicular torsion/detorsion damage in rats.Urol Int,2010,84(1):105-111.
[17]Groban L,Vernon JC,Butterworth J.Intrathecal morphine reduces infarct size in a rat model of ischemia-reperfnsion injury.Anesth Analg,2014,98(4):903-909.
[18]熊颖芬,金小雪,孟叶,等.阿片受体在瑞芬太尼减轻大鼠肾脏缺血再灌注损伤中的作用.中华麻醉学杂志,2012,32(7):877-879
[19]Huber TB,Edelstein CL,Hartleben B,et al.Emerging role of autophagy in kidney function,diseases and aging.Autophagy,2012,8(7):1009-1031.
[20]刘振臻,冷玉芳,李轩杰,等.羟考酮预先给药对大鼠肾缺血再灌注时自噬的影响.中华麻醉学杂志,2017,37(3):379-381.