极化液和丙酮酸钠联合治疗严重烫伤多器官功能不全综合征大鼠实验研究
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摘要
目的观察极化液和丙酮酸钠联合治疗严重烫伤多器官功能不全综合征(MODS)大鼠效果。方法 80只SD清洁级30%TBSAⅢ度烫伤MODS大鼠按随机数字表法分为极化液治疗组(GIK组)、丙酮酸钠治疗组(SP组)、极化液和丙酮酸钠联合治疗组(GIK+SP组)和对照组,每组20只,观察4组伤前、伤后1、3、5及7 d血糖(GLU)、乳酸(LA)、丙酮酸(PA)、可溶性髓样细胞触发蛋白1(s TREM-1)、高迁移率族蛋白B1(HMGB-1)和丙二醛(MDA)、超氧化物歧化酶(SOD)水平变化情况。结果 4组伤后各时点GLU、LA、LA/PA、s TREM-1、HMGB-1以及MDA水平均高于伤前(P<0.01),SOD水平均低于伤前(P<0.01);GIK组、SP组和GIK+SP组伤后各时点GLU、LA、PA、LA/PA、s TREM-1、HMGB-l及MDA水平低于对照组,PA、SOD水平均高于对照组(P<0.01);GIK+SP组伤后各时点GLU、LA、LA/PA、s TREM-1和HMGB-1以及MDA水平均低于GIK组和SP组,SOD均水平高于GIK组和SP组(P<0.01)。结论严重烫伤MODS大鼠存在高血糖、高乳酸血症、过度炎症反应和氧自由基损伤,极化液和丙酮酸钠具有改善高乳酸血症,降低LA/PA比值以及抗炎和抗氧化作用,且联合治疗比单独治疗效果更好,可作为防治严重烫伤后MODS重要措施。
Objective To observe effect of combination of glucose-insulin-potassium( GIK) combined with Sodium Pyruvate in treatment of rats with multiple organ dysfunction syndrome( MODS) induced by severe scald. Methods A total of 80 cleaning 30% total body surface area( TBSA) III scald SD MODS rats were divided into GIK treatment group( GIK group,n = 20),Sodium Pyruvate treatment group( SP group,n = 20),GIK combined with Sodium Pyruvate treatment group( group GIK + SP,n = 20) and control group( n = 20) according to random digits table method. Changes of blood glucose( GLU),lactic acid( LA),Pyruvate( PA),soluble myeloid cells trigger protein 1( s TREM-1),high mobility group protein B1( HMGB-1) and malondialdehyde( MDA),superoxide dismutase( SOD) levels before injury,1 d,3 d,5 d and 7 d after injury were observed. Results At all time points after injury,GLU,LA,LA/PA,s TREM-1,HMGB-1,and MDA levels were significantly higher( P < 0. 01),while SOD levels were significantly lower than those before injury in 4 groups( P < 0. 01). Compared with those in control group,GLU,LA,PA,LA/PA,s TREM-1,HMGB-1,and MDA levels were significantly lower,while PA and SOD levels were significantly higher in GIK,PA and GIK + PA groups at all time points after injury( P < 0. 01). In group GIK + SP,GLU,LA,LA/PA,s TREM-1,HMGBl,and MDA levels were significantly lower,while SOD levels were significantly higher at all time points after injury compared with those in GIK and SP groups( P < 0. 01). Conclusion MODS rats induced by severe scald have hyperglycemia,hyperlactacidemia,excessive inflammatory reaction and oxygen radicals injury. GIK and Sodium Pyruvate may improve hyperlactacidemia,reduce LA/PA ratio,anti-inflammatory and antioxidant effects,and combination therapy may achieve better effect than that by single therapy,and therefore GIK combined with Sodium Pyruvate may be uses as an important method in treatment of MODS rats induced by severe scald.
Objective To observe effect of combination of glucose-insulin-potassium( GIK) combined with Sodium Pyruvate in treatment of rats with multiple organ dysfunction syndrome( MODS) induced by severe scald. Methods A total of 80 cleaning 30% total body surface area( TBSA) III scald SD MODS rats were divided into GIK treatment group( GIK group,n = 20),Sodium Pyruvate treatment group( SP group,n = 20),GIK combined with Sodium Pyruvate treatment group( group GIK + SP,n = 20) and control group( n = 20) according to random digits table method. Changes of blood glucose( GLU),lactic acid( LA),Pyruvate( PA),soluble myeloid cells trigger protein 1( s TREM-1),high mobility group protein B1( HMGB-1) and malondialdehyde( MDA),superoxide dismutase( SOD) levels before injury,1 d,3 d,5 d and 7 d after injury were observed. Results At all time points after injury,GLU,LA,LA/PA,s TREM-1,HMGB-1,and MDA levels were significantly higher( P < 0. 01),while SOD levels were significantly lower than those before injury in 4 groups( P < 0. 01). Compared with those in control group,GLU,LA,PA,LA/PA,s TREM-1,HMGB-1,and MDA levels were significantly lower,while PA and SOD levels were significantly higher in GIK,PA and GIK + PA groups at all time points after injury( P < 0. 01). In group GIK + SP,GLU,LA,LA/PA,s TREM-1,HMGBl,and MDA levels were significantly lower,while SOD levels were significantly higher at all time points after injury compared with those in GIK and SP groups( P < 0. 01). Conclusion MODS rats induced by severe scald have hyperglycemia,hyperlactacidemia,excessive inflammatory reaction and oxygen radicals injury. GIK and Sodium Pyruvate may improve hyperlactacidemia,reduce LA/PA ratio,anti-inflammatory and antioxidant effects,and combination therapy may achieve better effect than that by single therapy,and therefore GIK combined with Sodium Pyruvate may be uses as an important method in treatment of MODS rats induced by severe scald.
引文
[1]周媛,王占科,祝仲珍,等.严重创伤失血多器官功能不全综合征患者胰岛β细胞功能与感染炎症和主要脏器功能的相关性[J].重庆医学,2017,46(29):4063-4066.
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[3]Wang Z K,Chen R J,Wang S L,et al.Clinical application of a novel diagnostic scheme including pancreaticβ-cell dysfunction for traumatic multiple organ dysfunction syndrome[J].Mol Med Rep,2018,17(1):683-693.
[4]刘筱蔼,曾萍,吴伟康,等.四逆汤对多器官功能障碍综合征大鼠炎症介质和氧化应激的影响[J].华中科技大学学报:医学版,2009,38(4):486-490.
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[7]陈荣剑,王占科,张晓云,等.胰岛素和丙酮酸乙酯联合治疗拮抗严重烫伤后MODS大鼠炎症反应和氧化应激的实验研究[J].解放军医药杂志,2015,27(8):45-50.
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[9]Wang Z,Liu L,Hu T,et al.Protective effect of glucose-insulin-potassium(GIK)on intestinal tissues after severe burn in experimental rats[J].Burns,2012,38(6):846-854.
[10]吴晓晴.动物实验基本操作技术手册[M].北京:人民军医出版社,2008:57-58.
[11]Chibalin A V,Kovalenko M V,Ryder J W,et al.Insulinand glucose-induced phosphorylation of the Na(+),K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle[J].Endocrinology,2001,142(8):3474-3482.
[12]Fan B S,Zhang E H,Wu M,et al.Activation of alpha7Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/KATPase Pathway[J].Front Pharmacol,2016,7:79.
[13]Sun Q,Li J,Gao F.New insights into insulin:The antiinflammatory effect and its clinical relevance[J].World J Diabetes,2014,5(2):89-96.
[14]赵国莉,吕肖峰,程千鹏.胰岛素泵治疗对初诊2型糖尿病患者血糖、血脂、氧化应激的影响及胰岛β细胞与超氧化物歧化酶的关系研究[J].中国全科医学,2012,15(25):2902-2904.
[15]Chen Q,Yu W,Shi J,et al.Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats[J].J Inflamm(Lond),2014,11:18.
[16]刘琪琳,陈斌,杨小霖,等.强化胰岛素治疗对体外循环炎症反应的影响[J].中国老年学杂志,2015,35(13):3570-3572.
[17]Jeschke M G,Kraft R,Song J,et al.Insulin protects against hepatic damage postburn[J].Mol Med,2011,17(5-6):516-522.
[18]Finfer S,Chittock D R,Su S Y,et al.Intensive versus conventional glucose control in critically ill patients[J].N Engl J Med,2009,360(13):1283-1297.
[19]解放军肾脏病研究所学术委员会.严重乳酸酸中毒伴多器官功能不全[J].肾脏病与透析肾移植杂志,2009,18(5):491-496.
[20]王占科,胡新勇,柴长春,等.创伤失血后多器官功能障碍综合征患者胰岛素抵抗和胰岛素分泌功能的变化及临床价值[J].中国危重病急救医学,2003,15(1):43-44.
[21]Su L,Liu D,Chai W,et al.Role of s TREM-1 in predicting mortality of infection:a systematic review and metaanalysis[J].BMJ Open,2016,6(5):e010314.
[22]Ueno T,Ikeda T,Ikeda K,et al.HMGB-1 as a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP[J].J Surg Res,2011,171(1):183-190.
[23]张晓云,陈荣剑,王占科,等.脓毒症氧化应激与抗氧化治疗研究进展[J/CD].中华临床医师杂志:电子版,2014,8(12):144-149.
[24]祝仲珍,蔺静,王占科,等.丙酮酸乙酯对严重烫伤内毒素血症大鼠炎症反应及氧化应激的作用[J].中华烧伤杂志,2014,30(5):443-446.
[25]周方强,刘锐.丙酮酸钠在危重病液体治疗中的潜在应用[J/CD].中华损伤与修复杂志:电子版,2017,12(5):321-325.
[26]张元芳,吴肇光,周方强.丙酮酸钠在缺氧型乳酸性酸中毒中的潜在临床应用[J].中华医学杂志,2015,(12):958-960.
[27]Liu R,Hu X H,Wang S M,et al.Pyruvate in oral rehydration salt improves hemodynamics,vasopermeability and survival after burns in dogs[J].Burns,2016,42(4):797-806.
[28]Bennett-Guerrero E,Swaminathan M,Grigore A M,et al.A phase ii multicenter double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass[J].J Cardiothorac Vasc Anesth,2009,23(3):324-329.
[29]Schillinger W,Hunlich M,Sossalla S,et al.Intracoronary pyruvate in cardiogenic shock as an adjunctive therapy to catecholamines and intra-aortic balloon pump shows beneficial effects on hemodynamics[J].Clin Res Cardiol,2011,100(5):433-438.
[2]石松菁.多器官功能障碍综合征诊治进展[J].中华急诊医学杂志,2013,22(8):824-826.
[3]Wang Z K,Chen R J,Wang S L,et al.Clinical application of a novel diagnostic scheme including pancreaticβ-cell dysfunction for traumatic multiple organ dysfunction syndrome[J].Mol Med Rep,2018,17(1):683-693.
[4]刘筱蔼,曾萍,吴伟康,等.四逆汤对多器官功能障碍综合征大鼠炎症介质和氧化应激的影响[J].华中科技大学学报:医学版,2009,38(4):486-490.
[5]Du J,Liu H,Liu R,et al.Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome[J].J Huazhong Univ Sci Technolog Med Sci,2011,31(2):194-198.
[6]王汉民,连耀国,刘宏宝,等.连续性血液净化对心脏术后多脏器功能障碍综合征患者炎性介质和氧化应激的影响[J].中国血液净化,2006,5(11):769-772.
[7]陈荣剑,王占科,张晓云,等.胰岛素和丙酮酸乙酯联合治疗拮抗严重烫伤后MODS大鼠炎症反应和氧化应激的实验研究[J].解放军医药杂志,2015,27(8):45-50.
[8]何蓉,姚德厚,李源.极化液在心肌缺血治疗中的研究进展[J].西南国防医药,2012,22(8):920-922.
[9]Wang Z,Liu L,Hu T,et al.Protective effect of glucose-insulin-potassium(GIK)on intestinal tissues after severe burn in experimental rats[J].Burns,2012,38(6):846-854.
[10]吴晓晴.动物实验基本操作技术手册[M].北京:人民军医出版社,2008:57-58.
[11]Chibalin A V,Kovalenko M V,Ryder J W,et al.Insulinand glucose-induced phosphorylation of the Na(+),K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle[J].Endocrinology,2001,142(8):3474-3482.
[12]Fan B S,Zhang E H,Wu M,et al.Activation of alpha7Nicotinic Acetylcholine Receptor Decreases On-site Mortality in Crush Syndrome through Insulin Signaling-Na/KATPase Pathway[J].Front Pharmacol,2016,7:79.
[13]Sun Q,Li J,Gao F.New insights into insulin:The antiinflammatory effect and its clinical relevance[J].World J Diabetes,2014,5(2):89-96.
[14]赵国莉,吕肖峰,程千鹏.胰岛素泵治疗对初诊2型糖尿病患者血糖、血脂、氧化应激的影响及胰岛β细胞与超氧化物歧化酶的关系研究[J].中国全科医学,2012,15(25):2902-2904.
[15]Chen Q,Yu W,Shi J,et al.Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats[J].J Inflamm(Lond),2014,11:18.
[16]刘琪琳,陈斌,杨小霖,等.强化胰岛素治疗对体外循环炎症反应的影响[J].中国老年学杂志,2015,35(13):3570-3572.
[17]Jeschke M G,Kraft R,Song J,et al.Insulin protects against hepatic damage postburn[J].Mol Med,2011,17(5-6):516-522.
[18]Finfer S,Chittock D R,Su S Y,et al.Intensive versus conventional glucose control in critically ill patients[J].N Engl J Med,2009,360(13):1283-1297.
[19]解放军肾脏病研究所学术委员会.严重乳酸酸中毒伴多器官功能不全[J].肾脏病与透析肾移植杂志,2009,18(5):491-496.
[20]王占科,胡新勇,柴长春,等.创伤失血后多器官功能障碍综合征患者胰岛素抵抗和胰岛素分泌功能的变化及临床价值[J].中国危重病急救医学,2003,15(1):43-44.
[21]Su L,Liu D,Chai W,et al.Role of s TREM-1 in predicting mortality of infection:a systematic review and metaanalysis[J].BMJ Open,2016,6(5):e010314.
[22]Ueno T,Ikeda T,Ikeda K,et al.HMGB-1 as a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP[J].J Surg Res,2011,171(1):183-190.
[23]张晓云,陈荣剑,王占科,等.脓毒症氧化应激与抗氧化治疗研究进展[J/CD].中华临床医师杂志:电子版,2014,8(12):144-149.
[24]祝仲珍,蔺静,王占科,等.丙酮酸乙酯对严重烫伤内毒素血症大鼠炎症反应及氧化应激的作用[J].中华烧伤杂志,2014,30(5):443-446.
[25]周方强,刘锐.丙酮酸钠在危重病液体治疗中的潜在应用[J/CD].中华损伤与修复杂志:电子版,2017,12(5):321-325.
[26]张元芳,吴肇光,周方强.丙酮酸钠在缺氧型乳酸性酸中毒中的潜在临床应用[J].中华医学杂志,2015,(12):958-960.
[27]Liu R,Hu X H,Wang S M,et al.Pyruvate in oral rehydration salt improves hemodynamics,vasopermeability and survival after burns in dogs[J].Burns,2016,42(4):797-806.
[28]Bennett-Guerrero E,Swaminathan M,Grigore A M,et al.A phase ii multicenter double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass[J].J Cardiothorac Vasc Anesth,2009,23(3):324-329.
[29]Schillinger W,Hunlich M,Sossalla S,et al.Intracoronary pyruvate in cardiogenic shock as an adjunctive therapy to catecholamines and intra-aortic balloon pump shows beneficial effects on hemodynamics[J].Clin Res Cardiol,2011,100(5):433-438.