胰岛素和川芎嗪联合治疗对严重烫伤内毒素血症大鼠血浆sTREM-1、sICAM-1、MDA和SOD水平的影响
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摘要
目的探讨胰岛素和川芎嗪单独和联合治疗对严重烫伤内毒素血症大鼠血浆可溶性髓样细胞触发蛋白-1(sTREM-1)、可溶性细胞间黏附分子-1(sICAM-1)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平影响,观察其抗炎和抗氧化效果。方法建立重度烫伤内毒素血症SD大鼠模型80只,按随机数字法随机分为胰岛素组(腹腔注射胰岛素)、川芎嗪组(腹腔注射川芎嗪)、联合组(腹腔注射胰岛素和川芎嗪)及对照组(腹腔注射生理盐水),各20只。测定各组伤前,伤后1、3、5和7 d血浆sTREM-1、ICAM-1、MDA和SOD水平变化。结果 4组伤后各时间点血sTREM-1和sICAM-1以及MDA水平均高于伤前(P<0.01),SOD水平低于伤前(P<0.01)。胰岛素组、川芎嗪组和联合组伤后各时间点血浆sTREM-1、sICAM-1以及MDA水平均低于对照组(P<0.01),SOD水平均高于对照组(P<0.01)。联合组伤后各时间点血浆sTREM-1、sICAM-1和MDA水平均低于胰岛素组和川芎嗪组(P<0.01),SOD水平均明显高于胰岛素组和川芎嗪组(P<0.01)。结论严重烫伤内毒素血症大鼠存在过度炎性反应和氧自由基损伤,胰岛素和川芎嗪具有抗炎和抗氧化作用,且联合治疗比单独治疗效果好;胰岛素和川芎嗪联合治疗可作为防治严重烫伤后过度炎性反应和氧化应激损伤的有效药物。
Objective To discuss effects of Insulin combined with Tetramethylpyrazine( TMP) therapy and every single one therapy on plasma soluble triggering receptor expressed on myeloid cells-1( sTREM-1),soluble intercellular adhesion molecule-1( sICAM-1),superoxide dismutase( SOD) malondialdehyde and( MDA) of rats with endotoximia after severe scalding injury,and to observe their anti-inflammatory and anti-oxidization effects. Methods A total of80 SD rat models with endotoximia after severe scalding injury were established,and were randomly divided into Insulin group( n = 20,intraperitoneal injection of Insulin),TMP group( n = 20,intraperitoneal injection of TMP),combined group( n = 20,intraperitoneal injection of Insulin and TMP) and control group( n = 20,intraperitoneal injection of physiological saline). Changes of plasma sTREM-1,ICAM-1,MDA and SOD levels were detected before and at 1st,3rd,5th and 7thd after injury in all groups. Results In the 4 groups,STREM-1,sICAM-1 and MDA levels at all time points after injury were significantly higher( P < 0. 01),while SOD levels were significantly lower than those before injury( P <0. 01). In Insulin group,TMP group and combined group,plasma sTREM-1,sICAM-1 and MDA levels were significantly lower( P < 0. 01),while SOD levels were significantly higher at all time point after injury than those in control group( P < 0. 01). In combined group,plasma sTREM-1,sICAM-1 and MDA levels were significantly lower( P < 0. 01),while SOD levels were significantly higher than those in Insulin and TMP groups( P < 0. 01). Conclusion Rats with endotoximia after sever scalding injury have exceeding inflammatory reaction and oxygen free radical damage. Insulin and TMP have anti-inflammatory and anti-oxidization effects,and the effect of combined therapy is better than those by every single one,and therefore Insulin combined with TMP can be used as an effective medication for exceeding inflammatory reaction and oxygen free radical damage after sever scalding injury.
Objective To discuss effects of Insulin combined with Tetramethylpyrazine( TMP) therapy and every single one therapy on plasma soluble triggering receptor expressed on myeloid cells-1( sTREM-1),soluble intercellular adhesion molecule-1( sICAM-1),superoxide dismutase( SOD) malondialdehyde and( MDA) of rats with endotoximia after severe scalding injury,and to observe their anti-inflammatory and anti-oxidization effects. Methods A total of80 SD rat models with endotoximia after severe scalding injury were established,and were randomly divided into Insulin group( n = 20,intraperitoneal injection of Insulin),TMP group( n = 20,intraperitoneal injection of TMP),combined group( n = 20,intraperitoneal injection of Insulin and TMP) and control group( n = 20,intraperitoneal injection of physiological saline). Changes of plasma sTREM-1,ICAM-1,MDA and SOD levels were detected before and at 1st,3rd,5th and 7thd after injury in all groups. Results In the 4 groups,STREM-1,sICAM-1 and MDA levels at all time points after injury were significantly higher( P < 0. 01),while SOD levels were significantly lower than those before injury( P <0. 01). In Insulin group,TMP group and combined group,plasma sTREM-1,sICAM-1 and MDA levels were significantly lower( P < 0. 01),while SOD levels were significantly higher at all time point after injury than those in control group( P < 0. 01). In combined group,plasma sTREM-1,sICAM-1 and MDA levels were significantly lower( P < 0. 01),while SOD levels were significantly higher than those in Insulin and TMP groups( P < 0. 01). Conclusion Rats with endotoximia after sever scalding injury have exceeding inflammatory reaction and oxygen free radical damage. Insulin and TMP have anti-inflammatory and anti-oxidization effects,and the effect of combined therapy is better than those by every single one,and therefore Insulin combined with TMP can be used as an effective medication for exceeding inflammatory reaction and oxygen free radical damage after sever scalding injury.
引文
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[18]张哲英,马莉.可溶性髓样细胞触发受体-1在脓毒症中的研究进展[J].中国急救医学,2013,33(10):951-954.
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[20]Li Z,Zhang E,Hu Y,et al.High serum s TREM-1 correlates with myocardial dysfunction and predicts prognosis in septic patients[J].Am J Med Sci,2016,351(6):555-562.
[21]郭英,瞿宁厚.细胞间粘附分子-1研究进展[J].陕西医学杂志,2008,37(4):492-494.
[22]Jander S,Heidenreich F,Stoll G.Serum and CSF levels of soluble intercellular adhesion molecule-1(ICAM-1)in inflammatory neurologic diseases[J].Neurology,1993,43(9):1809-1813.
[23]朱克军,黄洪,储辉,等.缺血预处理对大鼠创伤性脑损伤后脑组织细胞间黏附分子-1表达的影响[J].中华创伤杂志,2014,30(5):464-466.
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[26]Ingels C,Derese I,Wouters P J,et al.Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness:impact of glycemic control with insulin and relation with clinical outcome[J].Shock,2015,43(2):109-116.
[27]周虹,马俊勋,高诗博,等.胰岛素强化治疗对严重创伤患者炎症介质和外周血核转录因子κB的影响[J].临床急诊杂志,2014,15(12):709-712.
[28]师灵灵,韩艳秋.脓毒症相关凝血-炎症生物标志物研究进展[J].医学综述,2016,22(5):873-877.DOI:10.3969/j.issn.1006-2084.2016.05.012.
[29]丁欢,曹相原,马希刚,等.脓毒症内皮细胞损伤与炎症、凝血相关性研究[J].中华急诊医学杂志,2013,22(5):482-486.DOI:10.3760/cma.j.issn.1671-0282.2013.05.008.
[30]马淑媛,高芳.川芎嗪注射液治疗急性脑梗塞临床疗效观察[J].牡丹江医学院学报,2008,29(6):34-35.
[31]李慧君.血栓通联合川芎嗪治疗瘀血阻络型急性缺血性脑卒中的临床效果观察[J].中国当代医药,2015,22(5):157-158,161.
[32]王红娟.丹参川芎嗪针剂对急性脑梗死患者血清炎症因子的影响[J].中国实用神经疾病杂志,2015,18(24):63-64.DOI:10.3969/j.issn.1673-5110.2015.24.039.
[33]沈丽英,赵慧娣,吴少华.川芎嗪注射液治疗脑梗死疗效观察及对血浆L-选择素和TNF-α浓度的影响[J].放射免疫学杂志,2013,26(5):584-585.
[34]周艳,傅永锦,潘竞锵,等.川芎嗪对高脂高糖饮食与STZ诱致大鼠肾损伤保护作用的抗氧化机制[J].中国实验方剂学杂志,2011,17(23):199-202.
[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]刘胜蕊,史晓峰,王兵,等.腹腔感染性脓毒症可溶性髓样细胞触发受体(s TREM-1)与Janus激酶-信号转导和转录激活因子(JAK/STAT)通路的关系[J].中华急诊医学杂志,2016,25(3):314-319.
[4]王一贺,杨红明,胡泉,等.丙泊酚对烧冲复合伤犬外周血单个核细胞及细胞间黏附分子的影响[J].中华医学杂志,2014,94(20):1573-1576.
[5]杨新征,朱宝宇,于飞.严重创伤致多器官功能不全综合征的发病机制[J].局解手术学杂志,2013,22(6):663-664.
[6]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.
[7]Jeschke M G,Kraft R,Song J,et al.Insulin protects against hepatic damage postburn[J].Mol Med,2011,17(5-6):516-522.
[8]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.
[9]李金林,周姚,邹玲,等.强化胰岛素治疗对严重多发伤患者炎症介质和预后的影响[J].江苏医药,2014,40(4):474-476.
[10]王世龙,林原,唐泽耀.川芎嗪在各类神经系统损伤中的保护作用及其机理研究进展[J].中国药理学通报,2010,26(4):438-442.
[11]舒冰,周重建,马迎辉,等.中药川芎中有效成分的药理作用研究进展[J].中国药理学通报,2006,22(9):1043-1047.
[12]吴晋,陈益君,黄长顺.川芎嗪对老年患者体外循环心脏手术炎性反应及术后认知功能的影响[J].中国全科医学,2014,17(11):1262-1265.
[13]王占科,雷万生,柴长春,等.极化液对严重烫伤内毒素血症大鼠胰岛β细胞功能的影响[J].中华创伤杂志,2006,22(9):709-711.
[14]陈孝东,曹勇军,王引明,等.参芎注射液对大鼠脑缺血再灌注损伤的保护作用[J].国际脑血管病杂志,2006,14(4):270-274.
[15]王正国.实用创伤外科学[M].福州:福建科学技术出版社,2009:215-216.
[16]张晓云,陈荣剑,王占科.脓毒症氧化应激与抗氧化治疗研究进展[J].中华临床医师杂志:电子版,2014,8(12):144-149.
[17]Liu M,Zhang Y,Xiong J Y,et al.Etomidate mitigates lipopolysaccharide-induced CD14 and TREM-1 expression,NF-κB activation,and pro-inflammatory cytokine production in rat macrophages[J].Inflammation,2016,39(1):327-335.
[18]张哲英,马莉.可溶性髓样细胞触发受体-1在脓毒症中的研究进展[J].中国急救医学,2013,33(10):951-954.
[19]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.
[20]Li Z,Zhang E,Hu Y,et al.High serum s TREM-1 correlates with myocardial dysfunction and predicts prognosis in septic patients[J].Am J Med Sci,2016,351(6):555-562.
[21]郭英,瞿宁厚.细胞间粘附分子-1研究进展[J].陕西医学杂志,2008,37(4):492-494.
[22]Jander S,Heidenreich F,Stoll G.Serum and CSF levels of soluble intercellular adhesion molecule-1(ICAM-1)in inflammatory neurologic diseases[J].Neurology,1993,43(9):1809-1813.
[23]朱克军,黄洪,储辉,等.缺血预处理对大鼠创伤性脑损伤后脑组织细胞间黏附分子-1表达的影响[J].中华创伤杂志,2014,30(5):464-466.
[24]朱黎霞,王利胜,张英丰.丹参总酚酸、山楂总黄酮组分配伍对高脂血症大鼠血脂、超氧化物歧化酶及丙二醛的影响[J].中国医药导报,2014,11(20):9-12.
[25]褚万立,柴家科.严重烧伤后应激性高血糖及胰岛素强化治疗进展[J].中华损伤与修复杂志:电子版,2012,7(2):73-76.
[26]Ingels C,Derese I,Wouters P J,et al.Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness:impact of glycemic control with insulin and relation with clinical outcome[J].Shock,2015,43(2):109-116.
[27]周虹,马俊勋,高诗博,等.胰岛素强化治疗对严重创伤患者炎症介质和外周血核转录因子κB的影响[J].临床急诊杂志,2014,15(12):709-712.
[28]师灵灵,韩艳秋.脓毒症相关凝血-炎症生物标志物研究进展[J].医学综述,2016,22(5):873-877.DOI:10.3969/j.issn.1006-2084.2016.05.012.
[29]丁欢,曹相原,马希刚,等.脓毒症内皮细胞损伤与炎症、凝血相关性研究[J].中华急诊医学杂志,2013,22(5):482-486.DOI:10.3760/cma.j.issn.1671-0282.2013.05.008.
[30]马淑媛,高芳.川芎嗪注射液治疗急性脑梗塞临床疗效观察[J].牡丹江医学院学报,2008,29(6):34-35.
[31]李慧君.血栓通联合川芎嗪治疗瘀血阻络型急性缺血性脑卒中的临床效果观察[J].中国当代医药,2015,22(5):157-158,161.
[32]王红娟.丹参川芎嗪针剂对急性脑梗死患者血清炎症因子的影响[J].中国实用神经疾病杂志,2015,18(24):63-64.DOI:10.3969/j.issn.1673-5110.2015.24.039.
[33]沈丽英,赵慧娣,吴少华.川芎嗪注射液治疗脑梗死疗效观察及对血浆L-选择素和TNF-α浓度的影响[J].放射免疫学杂志,2013,26(5):584-585.
[34]周艳,傅永锦,潘竞锵,等.川芎嗪对高脂高糖饮食与STZ诱致大鼠肾损伤保护作用的抗氧化机制[J].中国实验方剂学杂志,2011,17(23):199-202.