肾上腺髓质素对缺血再灌注后肾功能的保护
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摘要
目的:探讨肾上腺髓质素(Adrenomedullin,ADM)对缺血再灌注后肾功能的保护作用。方法:在注射外源性ADM蛋白后,建立急性缺血再灌注肾损伤模型,观察ADM对肾功能和氧化损伤指标肌酐(Creatinine,Cr)、尿素氮(Blood Urea Nitrogen,BUN)、髓过氧化物酶(Myeloperoxidase,MPO)、丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide Dismutase,SOD)影响。结果:与I组比较,II组的Cr、BUN、MPO、MDA大幅升高(P<0.05),表明急性肾损伤造模成功。与II相比,III组BUN、MPO、MDA明显下降(P<0.05),表现出一定的保护作用。结论:ADM对缺血再灌注损伤后的肾功能具有一定的保护作用,其机制可能与减少中性粒细胞浸润,抑制膜脂质的氧化,促进微血管重生修复有关。
Objective: To investigate the protective effects of ADM on kidney suffering ischemia reperfusion.Methods: After an injection of exogenous ADM,acute ischemia reperfusion injury model was created.Renal function and oxidative stress indicators such as Creatinine(Cr),Blood Urea Nitrogen(BUN),Myeloperoxidase(MPO),Malondialdehyde(MDA),and Superoxide Dismutase(SOD) was observed to find whether there was protection offered by ADM.Results: Comparing with I group,the indicators of renal function and IR injury in II group such as Cr,BUN,MPO and MDA had a significant increase(P<0.05) which indicated the success of acute IR model.What's more,BUN,MPO and MDA in III group were significantly lower than II group(P<0.05).Conclusions: ADM had protective effects on kidney suffering ischemia reperfusion,the mechanism may be related to its decrease of neutrophil infiltration,inhibition on membrane lipid peroxidation and promotion of angiogenesis.
Objective: To investigate the protective effects of ADM on kidney suffering ischemia reperfusion.Methods: After an injection of exogenous ADM,acute ischemia reperfusion injury model was created.Renal function and oxidative stress indicators such as Creatinine(Cr),Blood Urea Nitrogen(BUN),Myeloperoxidase(MPO),Malondialdehyde(MDA),and Superoxide Dismutase(SOD) was observed to find whether there was protection offered by ADM.Results: Comparing with I group,the indicators of renal function and IR injury in II group such as Cr,BUN,MPO and MDA had a significant increase(P<0.05) which indicated the success of acute IR model.What's more,BUN,MPO and MDA in III group were significantly lower than II group(P<0.05).Conclusions: ADM had protective effects on kidney suffering ischemia reperfusion,the mechanism may be related to its decrease of neutrophil infiltration,inhibition on membrane lipid peroxidation and promotion of angiogenesis.
引文
[1]Tapuria N,Kumar Y,Habib M M,et al.Remote ischemic preconditioning:a novel protective method from ischemia reperfusion injury--a review[J].J Surg Res,2008,150(2):304-330
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[3]Kitamura K,Kangawa K,Eto T.Adrenomedullin and PAMP:discovery,structures,and cardiovascular functions[J].Microsc Res Tech,2002,57(1):3-13
[4]Ashizuka S,Inatsu H,Inagaki-Ohara K,et al.Adrenomedullin as a potential therapeutic agent for inflammatory bowel disease[J].Curr Protein Pept Sci,2013,14(4):246-255
[5]Dwivedi A J,Wu R,Nguyen E,et al.Adrenomedullin and adrenomedullin binding protein-1 prevent acute lung injury after gut ischemia-reperfusion[J].J Am Coll Surg,2007,205(2):284-293
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[7]Wever K E,Warle M C,Wagener F A,et al.Remote ischaemic preconditioning by brief hind limb ischaemia protects against renal ischaemia-reperfusion injury:the role of adenosine[J].Nephrol Dial Transplant,2011,26(10):3108-3117
[8]Yurdakul T,Kulaksizoglu H,Piskin M M,et al.Combination antioxidant effect of alpha-tocoferol and erdosteine in ischemia-reperfusion injury in rat model[J].Int Urol Nephrol,2010,42(3):647-655
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[10]Kosieradzki M,Rowinski W.Ischemia/reperfusion injury in kidney transplantation:mechanisms and prevention[J].Transplant Proc,2008,40(10):3279-3288
[11]Sanada S,Komuro I,Kitakaze M.Pathophysiology of myocardial reperfusion injury:preconditioning,postconditioning,and translational aspects of protective measures[J].Am J Physiol Heart Circ Physiol,2011,301(5):H1723-1741
[12]Becker L B.New concepts in reactive oxygen species and cardiovascular reperfusion physiology[J].Cardiovasc Res,2004,61(3):461-470
[13]Alkaitis M S,Crabtree M J.Recoupling the cardiac nitric oxide synthases:tetrahydrobiopterin synthesis and recycling[J].Curr Heart Fail Rep,2012,9(3):200-210
[14]Yellon D M,Hausenloy D J.Myocardial reperfusion injury[J].N Engl J Med,2007,357(11):1121-1135
[15]Li C,Jackson R M.Reactive species mechanisms of cellular hypoxiareoxygenation injury[J].Am J Physiol Cell Physiol,2002,282(2):C227-241
[16]Bonventre J V,Yang L.Cellular pathophysiology of ischemic acute kidney injury[J].J Clin Invest,2011,121(11):4210-4221
[17]Takei Y,Inoue K,Ogoshi M,et al.Identification of novel adrenomedullin in mammals:a potent cardiovascular and renal regulator[J].FEBS Lett,2004,556(1-3):53-58
[18]Hamid S A,Baxter G F.A critical cytoprotective role of endogenous adrenomedullin in acute myocardial infarction[J].J Mol Cell Cardiol,2006,41(2):360-363
[19]Martinez A.A new family of angiogenic factors[J].Cancer Lett,2006,236(2):157-163
[20]Muller-Redetzky H C,Will D,Hellwig K,et al.Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice:protection by adrenomedullin[J].Crit Care,2014,18(2):R73
[21]Sata M,Kakoki M,Nagata D,et al.Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism[J].Hypertension,2000,36(1):83-88
[22]Kataoka Y,Miyazaki S,Yasuda S,et al.The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction[J].J Cardiovasc Pharmacol,2010,56(4):413-419
[23]Nagaya N,Kyotani S,Uematsu M,et al.Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension[J].Circulation,2004,109(3):351-356
[24]Ashizuka S,Kita T,Inatsu H,et al.Adrenomedullin:a novel therapy for intractable ulcerative colitis[J].Inflamm Bowel Dis,2013,19(2):E26-27
[25]Nikitenko L L,Leek R,Henderson S,et al.The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis[J].Clin Cancer Res,2013,19(20):5740-5748
[26]Velho G,Ragot S,Mohammedi K,et al.Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes[J].Diabetes,2015,64(9):3262-3272
[2]Kitamura K,Kangawa K,Kawamoto M,et al.Adrenomedullin:a novel hypotensive peptide isolated from human pheochromocytoma[J].Biochem Biophys Res Commun,1993,192(2):553-560
[3]Kitamura K,Kangawa K,Eto T.Adrenomedullin and PAMP:discovery,structures,and cardiovascular functions[J].Microsc Res Tech,2002,57(1):3-13
[4]Ashizuka S,Inatsu H,Inagaki-Ohara K,et al.Adrenomedullin as a potential therapeutic agent for inflammatory bowel disease[J].Curr Protein Pept Sci,2013,14(4):246-255
[5]Dwivedi A J,Wu R,Nguyen E,et al.Adrenomedullin and adrenomedullin binding protein-1 prevent acute lung injury after gut ischemia-reperfusion[J].J Am Coll Surg,2007,205(2):284-293
[6]Kirisci M,Oktar G L,Ozogul C,et al.Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats[J].J Surg Res,2013,185(1):56-63
[7]Wever K E,Warle M C,Wagener F A,et al.Remote ischaemic preconditioning by brief hind limb ischaemia protects against renal ischaemia-reperfusion injury:the role of adenosine[J].Nephrol Dial Transplant,2011,26(10):3108-3117
[8]Yurdakul T,Kulaksizoglu H,Piskin M M,et al.Combination antioxidant effect of alpha-tocoferol and erdosteine in ischemia-reperfusion injury in rat model[J].Int Urol Nephrol,2010,42(3):647-655
[9]Munshi R,Hsu C,Himmelfarb J.Advances in understanding ischemic acute kidney injury[J].BMC Med,2011,9:11
[10]Kosieradzki M,Rowinski W.Ischemia/reperfusion injury in kidney transplantation:mechanisms and prevention[J].Transplant Proc,2008,40(10):3279-3288
[11]Sanada S,Komuro I,Kitakaze M.Pathophysiology of myocardial reperfusion injury:preconditioning,postconditioning,and translational aspects of protective measures[J].Am J Physiol Heart Circ Physiol,2011,301(5):H1723-1741
[12]Becker L B.New concepts in reactive oxygen species and cardiovascular reperfusion physiology[J].Cardiovasc Res,2004,61(3):461-470
[13]Alkaitis M S,Crabtree M J.Recoupling the cardiac nitric oxide synthases:tetrahydrobiopterin synthesis and recycling[J].Curr Heart Fail Rep,2012,9(3):200-210
[14]Yellon D M,Hausenloy D J.Myocardial reperfusion injury[J].N Engl J Med,2007,357(11):1121-1135
[15]Li C,Jackson R M.Reactive species mechanisms of cellular hypoxiareoxygenation injury[J].Am J Physiol Cell Physiol,2002,282(2):C227-241
[16]Bonventre J V,Yang L.Cellular pathophysiology of ischemic acute kidney injury[J].J Clin Invest,2011,121(11):4210-4221
[17]Takei Y,Inoue K,Ogoshi M,et al.Identification of novel adrenomedullin in mammals:a potent cardiovascular and renal regulator[J].FEBS Lett,2004,556(1-3):53-58
[18]Hamid S A,Baxter G F.A critical cytoprotective role of endogenous adrenomedullin in acute myocardial infarction[J].J Mol Cell Cardiol,2006,41(2):360-363
[19]Martinez A.A new family of angiogenic factors[J].Cancer Lett,2006,236(2):157-163
[20]Muller-Redetzky H C,Will D,Hellwig K,et al.Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice:protection by adrenomedullin[J].Crit Care,2014,18(2):R73
[21]Sata M,Kakoki M,Nagata D,et al.Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism[J].Hypertension,2000,36(1):83-88
[22]Kataoka Y,Miyazaki S,Yasuda S,et al.The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction[J].J Cardiovasc Pharmacol,2010,56(4):413-419
[23]Nagaya N,Kyotani S,Uematsu M,et al.Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension[J].Circulation,2004,109(3):351-356
[24]Ashizuka S,Kita T,Inatsu H,et al.Adrenomedullin:a novel therapy for intractable ulcerative colitis[J].Inflamm Bowel Dis,2013,19(2):E26-27
[25]Nikitenko L L,Leek R,Henderson S,et al.The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis[J].Clin Cancer Res,2013,19(20):5740-5748
[26]Velho G,Ragot S,Mohammedi K,et al.Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes[J].Diabetes,2015,64(9):3262-3272