乌司他丁对失血性休克大鼠肺组织损伤的保护作用
|
摘要
目的研究乌司他丁预处理对失血性休克大鼠肺组织损伤的保护作用。方法将雄性SD大鼠随机分为对照组、模型组和乌司他丁3、6万U/kg组,每组各8只。对照组、模型组通过尾静脉在20 min内微量泵注5 mL生理盐水,乌司他丁组尾iv 3、6万U/kg乌司他丁溶液5 mL。4 h后,按30 mL/kg经大鼠股动脉通道在10 min之内匀速抽取血液诱发失血性休克。维持休克状态60 min后,抽取的血液和乳酸林格氏液(30 mL/kg)在30 min内通过尾静脉匀速输注到大鼠体内复苏。在复苏后4 h测定大鼠肺组织超氧化物歧化酶(SOD)、丙二醛(MDA);采用Western blotting法检测Bcl-2、Bax和caspase-3蛋白表达量;测量支气管肺泡灌洗液(BAL)中的蛋白质和白细胞(WBC)含量。进行肺组织学观察。结果与模型组比较,6万U/kg乌司他丁预处理使肺组织SOD活性显著升高,MDA下降(P<0.05)。与模型组比较,6万U/kg乌司他丁预处理使肺组织Bcl-2表达显著上升,Bax和caspase-3表达显著减弱(P<0.05)。与模型组比较,6万U/kg乌司他丁预处理使肺组织BAL中蛋白、WBC含量显著减少(P<0.05)。结论 6万U/kg乌司他丁预处理对缺血再灌注大鼠肺损伤具有保护作用,其作用机制是改善肺组织的抗氧化作用。
Objective To study protective effects of ulinastatin pretreatment on lung tissue injury in hemorrhagic shock rats. Methods Male SD rats were randomly divided into control group, model group, and ulinastatin(30 000 and 60 000 U/kg) group, and each group had 8 rats. Rats in control group and model group were infused with 5 mL normal saline by tail vein in 20 min. Rats in ulinastatin groups were tail vein iv 5 mL ulinastatin solution 30 000 and 60 000 U/kg, respectively. After 4 h, 30 mL/kg of blood was extracted at a uniform rate through the femoral artery of the rats within 10 min to induce hemorrhagic shock. After the shock state was maintained for 60 min, the blood and Lactated Ringer's solution(30 mL/kg) were injected into the rats at a uniform rate through the tail vein for resuscitation within 30 min. After 4 h of recovery, SOD and MDA were determined, and the protein expressions of Bcl-2, Bax, and caspase-3 were determined by Western blotting method. Protein and WBC in BAL were measured, and the histopathological changes of lung were observed. Results Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase SOD activity and decreased MDA concentration in lung tissues(P < 0.05). Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase the expression of Bcl-2 in lung tissues, and decreased the expression of Bax and caspase-3(P < 0.05). Compared with the model group, the protein and WBC content in lung tissues were significantly reduced by 60 000 U/kg ulinastatin pretreatment(P < 0.05). Conclusion Ulinastatin pretreatment at 60 000 U/kg has a protective effect on lung injury in ischemia reperfusion rats, and the mechanism is to improve the antioxidant effect of lung tissue.
Objective To study protective effects of ulinastatin pretreatment on lung tissue injury in hemorrhagic shock rats. Methods Male SD rats were randomly divided into control group, model group, and ulinastatin(30 000 and 60 000 U/kg) group, and each group had 8 rats. Rats in control group and model group were infused with 5 mL normal saline by tail vein in 20 min. Rats in ulinastatin groups were tail vein iv 5 mL ulinastatin solution 30 000 and 60 000 U/kg, respectively. After 4 h, 30 mL/kg of blood was extracted at a uniform rate through the femoral artery of the rats within 10 min to induce hemorrhagic shock. After the shock state was maintained for 60 min, the blood and Lactated Ringer's solution(30 mL/kg) were injected into the rats at a uniform rate through the tail vein for resuscitation within 30 min. After 4 h of recovery, SOD and MDA were determined, and the protein expressions of Bcl-2, Bax, and caspase-3 were determined by Western blotting method. Protein and WBC in BAL were measured, and the histopathological changes of lung were observed. Results Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase SOD activity and decreased MDA concentration in lung tissues(P < 0.05). Compared with the model group, ulinastatin pretreatment at 60 000 U/kg could significantly increase the expression of Bcl-2 in lung tissues, and decreased the expression of Bax and caspase-3(P < 0.05). Compared with the model group, the protein and WBC content in lung tissues were significantly reduced by 60 000 U/kg ulinastatin pretreatment(P < 0.05). Conclusion Ulinastatin pretreatment at 60 000 U/kg has a protective effect on lung injury in ischemia reperfusion rats, and the mechanism is to improve the antioxidant effect of lung tissue.
引文
[1]Butti A.Recent developments in the physiopathology of hemorrhagic shock and current possibilities of its treatment[J].Chir Patol Sper,1969,17(5):373-404.
[2]Matthay M A,Zemans R L.The acute respiratory distress syndrome:pathogenesis and treatment[J].Annu Rev pathol,2011(6):147-163.
[3]Ware L B,Matthay M A.The acute respiratory distress syndrome[J].N Engl J Med,2000,342(18):1334-1349.
[4]李波,韩园园,王宴平,等.格列齐特对2型糖尿病大鼠心肌缺血预适应保护作用的影响[J].现代药物与临床,2014,29(7):711-716.
[5]刘伟,柴家科.乌司他丁对烧冲复合伤大鼠急性肺损伤及凝血参数时相性变化的影响[J].中华烧伤杂志,2018,34(1):32-39.
[6]钟娃,蒋龙元,姜骏,等.乌司他丁对失血性休克大鼠血流动力学及多器官保护的研究[J].中山大学学报,2006,27(3S):49-51
[7]刘洪恩,王海龙,蒋志伟,等.腹膜淋巴回流途径在腹腔感染早期内毒素肺损伤中的作用[J].广东医学,2015,36(21):3330-3333.
[8]Oliva J.Proteasome and organs ischemia-reperfusion injury[J].Int J Mol Sci,2017,19(1):E106.
[9]Lenaz G.Role of mitochondria in oxidative stress and ageing[J].Biochim Biophys Acta,1998,1366(1-2):53-67.
[10]Xiao J,Rui Q,Guo Y,et al.Prolonged manganese exposure induces severe deficits in lifespan,development and reproduction possibly by altering oxidative stress response in caenorhabditis elegans[J].J Environ Sci,2009,21(6):842-848.
[11]Benov L,Batinic-Haberle I.A manganese porphyrin suppresses oxidative stress and extends the life span of streptozotocin-diabetic rats[J].Free Radic Res,2005,39(1):81-88.
[12]曹玥,陈虎,陈凯,等.乌司他丁对糖尿病脓毒症大鼠急性肾损伤的保护作用[J].安徽医药,2018,22(2):228-231.
[13]李雪,赵明智,张安易,等.番茄红素对大鼠肺缺血再灌注损伤的保护作用研究[J].现代药物与临床,2015,30(6):637-641.
[14]Yousefi H,Ahmadiasl N,Alihemmati A,et al.Effect of renal ischemia-reperfusion on lung injury and inflammatory responses in male rat[J].Iran J Basic Med Sci,2014,17(10):802-807.
[15]Zhang C,Guo Z,Liu H,et al.Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury[J].PloS One,2015,10(1):e0114963.
[16]Haunstetter A,Izumo S.Apoptosis:basic mechanisms and implications for cardiovascular disease[J].Circ Res,1998,82(11):1111-1129.
[17]乔霖,赵薇,王新生,等.丙泊酚对大鼠脑缺血再灌注损伤的保护作用及其Caspase-3表达干预机制的研究[J].现代药物与临床,2015,30(6):629-632.
[18]van Heerde W L,Robert-Offerman S,Dumont E,et al.Markers of apoptosis in cardiovascular tissues:focus on Annexin V[J].Cardiovasc Res,2000,45(3):549-559.
[19]Veena V K,Popavath R N,Kennedy K,et al.In vitro antiproliferative,pro-apoptotic,antimetastatic and antiinflammatory potential of 2,4-diacetylphloroglucinol(DAPG)by Pseudomonas aeruginosa strain FP10[J].Apoptosis,2015,20(10):1281-1295.
[2]Matthay M A,Zemans R L.The acute respiratory distress syndrome:pathogenesis and treatment[J].Annu Rev pathol,2011(6):147-163.
[3]Ware L B,Matthay M A.The acute respiratory distress syndrome[J].N Engl J Med,2000,342(18):1334-1349.
[4]李波,韩园园,王宴平,等.格列齐特对2型糖尿病大鼠心肌缺血预适应保护作用的影响[J].现代药物与临床,2014,29(7):711-716.
[5]刘伟,柴家科.乌司他丁对烧冲复合伤大鼠急性肺损伤及凝血参数时相性变化的影响[J].中华烧伤杂志,2018,34(1):32-39.
[6]钟娃,蒋龙元,姜骏,等.乌司他丁对失血性休克大鼠血流动力学及多器官保护的研究[J].中山大学学报,2006,27(3S):49-51
[7]刘洪恩,王海龙,蒋志伟,等.腹膜淋巴回流途径在腹腔感染早期内毒素肺损伤中的作用[J].广东医学,2015,36(21):3330-3333.
[8]Oliva J.Proteasome and organs ischemia-reperfusion injury[J].Int J Mol Sci,2017,19(1):E106.
[9]Lenaz G.Role of mitochondria in oxidative stress and ageing[J].Biochim Biophys Acta,1998,1366(1-2):53-67.
[10]Xiao J,Rui Q,Guo Y,et al.Prolonged manganese exposure induces severe deficits in lifespan,development and reproduction possibly by altering oxidative stress response in caenorhabditis elegans[J].J Environ Sci,2009,21(6):842-848.
[11]Benov L,Batinic-Haberle I.A manganese porphyrin suppresses oxidative stress and extends the life span of streptozotocin-diabetic rats[J].Free Radic Res,2005,39(1):81-88.
[12]曹玥,陈虎,陈凯,等.乌司他丁对糖尿病脓毒症大鼠急性肾损伤的保护作用[J].安徽医药,2018,22(2):228-231.
[13]李雪,赵明智,张安易,等.番茄红素对大鼠肺缺血再灌注损伤的保护作用研究[J].现代药物与临床,2015,30(6):637-641.
[14]Yousefi H,Ahmadiasl N,Alihemmati A,et al.Effect of renal ischemia-reperfusion on lung injury and inflammatory responses in male rat[J].Iran J Basic Med Sci,2014,17(10):802-807.
[15]Zhang C,Guo Z,Liu H,et al.Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury[J].PloS One,2015,10(1):e0114963.
[16]Haunstetter A,Izumo S.Apoptosis:basic mechanisms and implications for cardiovascular disease[J].Circ Res,1998,82(11):1111-1129.
[17]乔霖,赵薇,王新生,等.丙泊酚对大鼠脑缺血再灌注损伤的保护作用及其Caspase-3表达干预机制的研究[J].现代药物与临床,2015,30(6):629-632.
[18]van Heerde W L,Robert-Offerman S,Dumont E,et al.Markers of apoptosis in cardiovascular tissues:focus on Annexin V[J].Cardiovasc Res,2000,45(3):549-559.
[19]Veena V K,Popavath R N,Kennedy K,et al.In vitro antiproliferative,pro-apoptotic,antimetastatic and antiinflammatory potential of 2,4-diacetylphloroglucinol(DAPG)by Pseudomonas aeruginosa strain FP10[J].Apoptosis,2015,20(10):1281-1295.