醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

徐志鹏; 陈硬; 宋琦; 李启梁; 朱恒; 邱兆磊; 纪忠; 王振杰

doi:10.13898/j.cnki.issn.1000-2200.2018.10.016

醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

蚌埠医学院第一附属医院急诊外科, 安徽蚌埠 233004

作者简介: 徐志鹏(1992-),男,硕士研究生.

基金项目:
安徽省科技计划攻关项目（1604a0802089）；安徽省高校自然科学研究项目（kj2015b092by）；研究生科研创新计划（Byycx1762）
中图分类号: R605.971

Effect of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats

Department of Emergency Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui 233004, China
CLC number: R605.971

摘要: 目的：探讨醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响。方法：将24只SD大鼠随机分为：失血性休克未复苏组（CR组），醋酸钠林格液组（AR组）和醋酸钠林格液联合乌司他丁组（WA组），每组8只。建立失血性休克大鼠模型，利用RT-PCR法检测肝组织中TNF-α mRNA、IL-4 mRNA及IL-10 mRNA相对表达量；利用Western Blot法检测肝组织p65（Ser536）磷酸化和p65（Lys310）乙酰化蛋白相对表达量；在光镜下进行3组肝组织形态学观察。结果：肝组织病理学结果显示WA组肝组织损伤程度轻于CR组与AR组；在肝组织中，与CR组及AR组比较，WA组TNF-α mRNA表达减少（P<0.01和P<0.05），IL-4 mRNA表达增加（P<0.01和P<0.05），IL-10 mRNA表达增加（P<0.01和P<0.05）；与CR组及AR组相比，WA组p65（Ser536）磷酸化蛋白水平表达降低（P<0.05）；与CR组及AR组相比，WA组p65（Lys310）乙酰化蛋白水平表达降低（P<0.05）。结论：醋酸钠林格液联合乌司他丁可能通过降低NF-κB p65蛋白活化、降低促炎因子TNF-α水平及提升抗炎因子IL-4和IL-10水平，减轻失血性休克大鼠的肝损伤。
- 失血性休克 /
- 肝损伤 /
- 醋酸钠林格液 /
- 乌司他丁 /
- NF-κB p65
Abstract: Objective:To investigate the effects of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats.Methods:Twenty-four SD rats were randomly divided into the hemorrhagic shock without resuscitation group(CR group),acetate ringer's solution group(AR group) and sodium acetate ringer's solution combined with ulinastatin group(WA group)(8 rats each group).A rat model of hemorrhagic shock was established.The expression levels of TNF-α mRNA,IL-4 mRNA and IL-10 mRNA in liver tissue were detected using RT-PCR.The relative expression levels of p65(Ser536) phosphorylation and p65(Lys310) acetylated protein in liver tissue were detected by Western Blot.The liver tissue morphology in three groups were observed under light microscope.Results:Liver histopathology results showed that the degree of liver tissue damage in WA group was lighter than that in CR group and AR group.In liver tissue,compared with CR group and AR group,the TNF-α mRNA expression decreased in WA group(P<0.01 and P<0.05),the IL-4 mRNA expression increased(P<0.01 and P<0.01) and the IL-10 mRNA expression increased(P<0.01 and P<0.05).Compared with CR group and AR group,the expression level of p65(Ser536) phosphorylated protein decreased in WA group(P<0.05).Compared with CR group and AR group,the expression level of p65(Lys310) acetylated protein decreased in WA group(P<0.05).Conclusions:Sodium acetate ringer's solution combined with ulinastatin alleviates liver injury in hemorrhagic shock rats,which may be through reducing NF-κB p65 protein activation,reducing pro-inflammatory factor TNF-α level,and enhancing anti-inflammatory factors IL-4 and IL-10 level.
- hemorrhagic shock /
- liver injury /
- acetate ringer's solution /
- ulinastatin /
- NF-κB p65

[1]	PFEIFER R,TSCHERNIG T,LICHTE P,et al.MALP-2 pre-treatment modulates systemic inflammation in hemorrhagic shock[J].J Inflamm(Lond),2013,10(1):17.
[2]	LEE CC,CHANG IJ,YEN ZS,et al.Delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine response[J].Annals Emergency Med,2007,49(1):37.
[3]	CANNON JW.Hemorrhagic shock[J].N Engl J Med,2018,378(4):370.
[4]	VEITH NT,HISTING T,MENGER MD,et al.Helping prometheus:liver protection in acute hemorrhagic shock[J].Ann Transl Med,2017,5(10):206.
[5]	宋琦,徐志鹏,王振杰,等.醋酸钠林格液复苏失血性休克大鼠对肺炎性介质及其信号通路的影响[J].中华急诊医学杂志,2018,27(6):638.
[6]	LIU FC,CHAUDRY IH.Hepatoprotective effects of corilagin following hemorrhagic shock are through Akt-dependent pathway[J].Shock (Augusta,Ga.),2017,47(3):346.
[7]	EL-TAHAN RR,GHONEIM AM.TNF-α gene polymorphisms and expression[J].Springer Plus,2016,5(1):1508.
[8]	蔡腾,王振杰,王林,等.乳酸钠林格液和醋酸钠林格液复苏对失血性休克大鼠TNF-α、IL-6和IL-10的影响[J].中国急救医学,2016,36(2):166.
[9]	吴颖,崔朝勃,亢宏山,等.乌司他丁对脓毒症患者血清肿瘤坏死因子-α、白细胞介素10、肌钙蛋白I和C反应蛋白水平的影响[J].蚌埠医学院学报,2016,41(12):1635.
[10]	LOZANO R,NAGHAVI M,FOREMAN K,et al.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010:a systematic analysis for the Global Burden of Disease Study 2010[J].Lancet (London,England),2012,380(9859):2095.
[11]	HAYAKAWA M,KATABAMI K,WADA T,et al.Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with blunt trauma[J].Inflammat,2011,34(3):193.
[12]	KARMANIOLOU Ⅱ,THEODORAKI KA,ORFANOS NF,et al.Resuscitation after hemorrhagic shock:the effect on the liver——a review of experimental data[J].J Anesthesia,2013,27(3):447.
[13]	KUMAR L,SEETHARAMAN M,RAJMOHAN N,et al.Metabolic profile in right lobe living donor hepatectomy:Comparison of lactated Ringer's solution and normal saline versus ac-etate based balanced salt solution a pilot study[J].Indian J Anaesthesia,2016,60(10):719.
[14]	KUSZA K,MIELNICZUK M,KROKOWICZ L,et al.Ringer's lactate solution enhances the inflammatory response during fluid resuscitation of experimentally induced haemorrhagic shock in rats[J].Archives Med Sci,2018,14(3):655.
[15]	鄢涛,谭鸿,姜伟,等.乌司他丁对失血性休克大鼠肝脏缺血再灌注损伤保护作用的研究[J].中国现代普通外科进展,2010,13(1):9.
[16]	SHARMA V,JORDAN JJ,CIRIBILLI Y,et al.Quantitative analysis of NF-κB transactivation specificity using a yeast-Based functional assay[J].PloS One,2015,10(7):e0130170.
[17]	SASAKI CY,BARBERI TJ,GHOSH P,et al.Phosphorylation of RelA/p65 on S536 defines an IkB-aindependent NF-κB pathway[J].J Biol Chem,2001,280(41):34538.
[18]	CHEN LF,WILLIAMS SA,MU Y,et al.NF-kappaB RelA phosphorylation regulates RelA acetylation[J].Mol Cell Biol,2005,25(18):7966.
[19]	BHATT D.Regulation of the NF-κB-mediated transcription of inflammatory genes[J].Frontiers in immunology,2014,5:71.
[20]	WU X,XU W,FENG X,et al.TNF-α mediated inflammatory macrophage polarization contributes to the pathogenesis of steroid-induced osteonecrosis in mice[J].Int J Immunopathol Pharmacol,2015,28(3):351.
[21]	LIU FC,YU HP,HWANG TL.Protective effect of tropisetron on rodent hepatic injury after trauma-hemorrhagic shock through P38 MAPK-dependent hemeoxygenase-1 expression[J].PloS One,2012,7(12):e53203.
[22]	SCHTZE S,WIEGMANN K,MACHLEIDT T.TNF-induced activation of NF-kappa B[J].Immunobiology,1995,193(2/4):193.
[23]	HE L,WANG B,YAO Y,et al.Protective effects of the SEPS1 gene on lipopolysaccharide-induced sepsis[J].Mol Med Rep,2014,9(5):1869.
[24]	LING L,WEN QK,ZHANG SH,et al.Continuous blood purification ameliorates multiple organ failure through inhibiting the activation of the P38 MAPK signaling pathway in a rat model[J].Kidney Blood Pressure Research,2018,43(3):938.
[25]	ZHANG YF,ZOU XL,WU J,et al.Rosiglitazone,a peroxisome proliferator-activated receptor(PPAR)-γ agonist,attenuates inflammation via NF-κB inhibition in lipopolysacch aride-induced peritonitis[J].Inflammation,2015,38(6):2105.
[26]	BELINGA VF,WU GJ,YAN FL.Splenectomy following MCAO inhibits the TLR4-NF-κB signaling pathway and protects the brain from neurodegeneration in rats[J].J Neuroimmunol,2016,293:105.

[1]	王振杰 , 陈硬 , 宋琦 , 徐志鹏 , 纪忠 , 邱兆磊 , 郑传明 , 李磊 , 程峰 . 乌司他丁通过miR-146a调节TLR4/NF-κB信号通路减轻失血性休克大鼠肾炎性损伤研究. 蚌埠医学院学报, 2020, 45(3): 286-290, 295. doi: 10.13898/j.cnki.issn.1000-2200.2020.03.002
[2]	王振杰 , 徐志鹏 , 陈硬 , 宋琦 . 醋酸钠林格液对失血性休克大鼠心肌炎性介质及NF-κB、MAPK信号通路的影响. 蚌埠医学院学报, 2020, 45(3): 281-285. doi: 10.13898/j.cnki.issn.1000-2200.2020.03.001
[3]	李磊 , 徐志鹏 , 夏群 , 邱兆磊 , 程峰 , 窦贺贺 , 姜海 , 宋琦 , 王振杰 . 醋酸钠林格液复苏联合乳酸菌对创伤失血性休克大鼠肠黏膜屏障的保护作用. 蚌埠医学院学报, 2021, 46(6): 708-712. doi: 10.13898/j.cnki.issn.1000-2200.2021.06.002
[4]	陶言言 , 齐本权 , 张弘 , 陆国玉 , 吴晓飞 . 参附注射液联合乌司他丁治疗脓毒症的疗效观察. 蚌埠医学院学报, 2020, 45(5): 581-584. doi: 10.13898/j.cnki.issn.1000-2200.2020.05.006
[5]	温暖 , 邬善敏 , 陈志波 , 卢超 , 蔡杰 . 肝切除术早期应用乌司他丁临床疗效的Meta分析. 蚌埠医学院学报, 2012, 36(1): 38-42.
[6]	张宝民 , 孙艳 , 徐继来 , 潘利平 . 乌司他丁治疗急性肺损伤/急性呼吸窘迫综合征34例临床分析. 蚌埠医学院学报, 2009, 34(12): 1108-1110.
[7]	袁晓宇 , 袁菊萍 , 黄中伟 . 血必净对热休克蛋白90在脓毒症小鼠肝肺损伤中表达的影响. 蚌埠医学院学报, 2016, 41(6): 717-721. doi: 10.13898/j.cnki.issn.1000-2200.2016.06.004
[8]	吴颖 , 崔朝勃 , 亢宏山 , 赵媛媛 , 刘淑红 . 乌司他丁对脓毒症患者血清肿瘤坏死因子-α、白细胞介素10、肌钙蛋白I和C反应蛋白水平的影响. 蚌埠医学院学报, 2016, 41(12): 1635-1638. doi: 10.13898/j.cnki.issn.1000-2200.2016.12.031
[9]	朱恒 , 李启梁 , 王振杰 , 纪忠 , 邱兆磊 . 不同液体限制性复苏对失血性休克病人血栓弹力图及凝血功能的影响. 蚌埠医学院学报, 2020, 45(3): 296-299. doi: 10.13898/j.cnki.issn.1000-2200.2020.03.004
[10]	李云翔 . 目标导向液体治疗对异位妊娠失血性休克患者围手术期心肌酶谱的影响. 蚌埠医学院学报, 2016, 41(4): 475-478. doi: 10.13898/j.cnki.issn.1000-2200.2016.04.016
[11]	李启梁 , 朱恒 , 邱兆磊 , 纪忠 , 王振杰 . 不同液体限制性复苏对创伤失血性休克病人外周血Th17和Treg细胞比例的影响. 蚌埠医学院学报, 2020, 45(3): 291-295. doi: 10.13898/j.cnki.issn.1000-2200.2020.03.003
[12]	陆德锟 , 黄奕江 , 齐晓林 , 黄峻松 , 邵先安 , 徐长江 , 马宏昊 , 郝建 . 血必净对水下爆炸致兔急性闭合性肝损伤早期干预的效果研究. 蚌埠医学院学报, 2019, 44(2): 150-153. doi: 10.13898/j.cnki.issn.1000-2200.2019.02.003
[13]	朱锡玲 , 张翠玲 , 刘浩 , 余美玲 . 金匮护肝汤对四氯化碳引起小鼠急性肝损伤的保护作用. 蚌埠医学院学报, 2013, 37(3): 262-263,267.
[14]	王博 , 吴俊英 , 徐超 . CD137表达与慢性乙型肝炎患者肝脏免疫病理损伤程度的相关性研究. 蚌埠医学院学报, 2016, 41(9): 1125-1128. doi: 10.13898/j.cnki.issn.1000-2200.2016.09.002
[15]	邱兆磊 , 王振杰 , 刘牧林 , 黄建康 , 董慧明 , 郑士友 . 抗肿瘤坏死因子-α单克隆抗体对阻塞性黄疸大鼠肝脏保护作用的实验研究. 蚌埠医学院学报, 2006, 31(3): 235-237.
[16]	赵亨 , 邱兆磊 , 王振杰 , 程峰 , 纪忠 , 张福龙 , 李磊 , 宋琦 , 徐志鹏 , 王如意 , 王世杰 , 张怀胜 , 徐远 . 乌司他丁联合参附注射液对重症急性胰腺炎心肌损伤的保护作用. 蚌埠医学院学报, 2022, 47(5): 596-599. doi: 10.13898/j.cnki.issn.1000-2200.2022.05.009
[17]	赵德俊 , 张福龙 , 徐志鹏 , 宋琦 , 姜海 , 李磊 , 邱兆磊 , 纪忠 , 王振杰 . 碳酸氢钠林格液限制性复苏对创伤失血性休克内环境的影响. 蚌埠医学院学报, 2021, 46(4): 447-450. doi: 10.13898/j.cnki.issn.1000-2200.2021.04.007
[18]	李晶晶 , 祖磊 , 薛鹏程 . TR3受体激动剂6-mercaptopurine对糖尿病ApoE^-/-小鼠NF-κB p65/CylinD1通路影响及其与抗动脉硬化关系. 蚌埠医学院学报, 2019, 44(9): 1137-1142. doi: 10.13898/j.cnki.issn.1000-2200.2019.09.001
[19]	王振杰 , 李磊 , 邱兆磊 , 纪忠 . 限制性液体复苏联合血必净注射液对失血未控制性休克兔失血量及复苏液体量的影响. 蚌埠医学院学报, 2013, 37(1): 12-15.
[20]	张云 . 纠正亚低温联合限制性液体复苏在严重腹部创伤合并失血性休克中的应用. 蚌埠医学院学报, 2016, 41(9): 1204-1206. doi: 10.13898/j.cnki.issn.1000-2200.2016.09.027

点击查看大图

计量

文章访问数: 3334
HTML全文浏览量: 549
PDF下载量: 34
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

作者简介: 徐志鹏(1992-),男,硕士研究生.

Effect of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats

计量

醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

作者简介: 徐志鹏(1992-),男,硕士研究生.

English Abstract

Effect of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats

全文HTML

目录

留言板

醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

作者简介: 徐志鹏(1992-),男,硕士研究生.

Effect of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats

计量

出版历程

醋酸钠林格液联合乌司他丁对失血性休克大鼠肝组织NF-κB p65蛋白表达及其细胞因子的影响

作者简介: 徐志鹏(1992-),男,硕士研究生.

English Abstract

Effect of sodium acetate ringer's solution combined with ulinastatin on the expression of NF-κB p65 protein and cytokines in liver tissue of hemorrhagic shock rats

全文HTML

目录