Effect of ulinastatin combined with ischemic preconditioning on hepatic ischemia-reperfusion injury in rats
-
摘要:
目的探讨乌司他丁(UTI)预处理和缺血预处理(IPC)联合应用对大鼠肝缺血再灌注损伤的影响及可能的作用机制。方法选择雄性SD大鼠50只,随机分为5组,分别为对照(sham)组、缺血再灌注(IR)组、IPC组、UTI组、UTI联合缺血预处理(UCI)组。术后采集下腔静脉血并取肝组织标本,检测血清AST、ALT、TNFɑ,肝组织髓过氧化物酶(MPO)、NF-κB、肝组织湿干比(W/D)及光镜观察肝组织病理形态学变化。计量资料组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果所检测的血清ALT、AST、TNFα水平和肝组织MPO、NF-κB、W/D值,IR组、IPC组、UTI组、UCI组均明显高于sham组(P值均<0.05),而IPC组、UTI组、UCI组均明显低于IR组(P值均<0.05),UTI组明显低于IPC组(P值均<0.05),UCI组明显低于IPC组、UTI组(P值均<0.05)。肝脏病理学检查示IR组、IPC组、UTI组、UCI组与sham组比较,肝组织损伤明显(P值均<0.05),而IPC组、UTI组、UCI组均比IR组肝组织损...
-
关键词:
- 乌司他丁 /
- 肝疾病 /
- 缺血预处理 /
- 再灌注损伤 /
- 大鼠,Sprague-Dawley
Abstract:Objective To investigate the effect of ulinastatin (UTI) preconditioning combined with ischemic preconditioning (IPC) on hepatic ischemia-reperfusion (IR) injury in rats and possible mechanism of action.Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group, IR group, IPC group, UTI group, and UTI-IPC group (UCI group) .Blood samples were collected from the inferior vena cava after surgery and liver tissue samples were also collected.The serum levels of aspartate aminotransferase (AST) , alanine aminotransferase (ALT) , and tumor necrosis factor-α (TNF-α) , the levels of myeloperoxidase (MPO) and nuclear factor-kappa B (NF-κB) in the liver tissue, and wet/dry weight ratio were determined, and pathomorphological changes of the liver tissue were observed under a light microscope.A one-way analysis of variance was used for comparison of continuous data between groups, and the LSD-t-test was used for further comparison between two groups.Results The IR, IPC, UTI, and UCI groups had significantly higher serum levels of ALT, AST, and TNF-α, levels of MPO and NF-κB in the liver tissue, and wet/dry weight ratio than the sham-operation group (all P < 0.05) ; the IPC, UTI, and UCI groups had significantly lower levels than the IR group (all P < 0.05) , the UTI group had significantly lower levels than the IPC group (all P < 0.05) , and the UCI group had significantly lower levels than the IPC and UTI groups (all P < 0.05) .Liver pathological examination showed that compared with the sham-operation group, the IR, IPC, UTI, and UCI groups had significantly greater liver injury (all P < 0.05) , while the IPC, UTI, and UCI groups had a significantly lower degree of liver injury than the IR group (all P < 0.05) , the UTI group had significantly slighter liver injury than the IPC group (P < 0.05) , and the UCI group had significantly slighter liver injury than the IPC and UTI groups (both P < 0.05) .Conclusion Both UTI and UCI have a protective effect against hepatic IR injury, and the combination of UTI and UCI significantly enhances such protective effect, possibly by inhibiting the expression of NF-κB, reducing the release of TNF-α and MPO, and alleviating liver inflammatory response.
-
Key words:
- ulinastatin /
- liver diseases /
- ischemic preconditioning /
- reperfusion injury /
- rats, Sprague-Dawley
-
[1]TEOH NC, FARRELL GC.Hepatic ischemia reperfusion injury:pathogenic mechanisms and basis for hepatic protection[J].J Gastroenterol Hepatol, 2003, 18 (8) :891-902. [2]MENGER MD, RICHTER S, YAMAUCHI J, et al.Role of microcirculation in hepatic ischemia-reperfusion injury[J].Hepatogastroenterology, 1999, 4 (6) :1452-1457. [3]CHEN WX, YANG LQ.Ulinastatin attenuates the inflammatory reaction induced by hepatic ischemia reperfusion in rats[J].Chin J Clin Med, 2012, 19 (3) :259-261. (in Chinese) 陈伟新, 杨立群.乌司他丁对大鼠肝脏缺血再灌注损伤后炎性反应的影响[J].中国临床医学, 2012, 19 (3) :259-261. [4]MA YF, LI XC, YAO AH, et al.Effect of ischemic preconditioning on nuclear factor-κB activation during early reperfusion following orthotopic liver transplantation in rats[J].Chin J Bases Clin Gen Surg, 2006, 13 (5) :531-534. (in Chinese) 马跃峰, 李相成, 姚爱华, 等.缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义[J].中国普外基础与临床杂志, 2006, 13 (5) :531-534. [5]ZHONG YJ, LIU ZM, HUANG YP, et al.Study on application of ulinastatin combined with tetrandrine for reperfusion of ischemic rat liver[J].J Clin Exp Med, 2016, 15 (5) :412-415. (in Chinese) 钟毓杰, 刘忠民, 黄永平, 等.乌司他丁联合粉防己碱在大鼠肝缺血再灌注中的应用研究[J].临床和实验医学杂志, 2016, 15 (5) :412-415. [6]KONG R, SUN B, PAN SH, et al.Protective effect of ischemia pretreatment in combination with salvianolic acid B[J].Chin J Hepatobiliary Surg, 2010, 16 (12) :951-953. (in Chinese) 孔瑞, 孙备, 潘尚哈, 等.缺血预处理联合丹酚酸B对大鼠肝脏缺血再灌注损伤的保护作用[J].中华肝胆外科杂志, 2010, 16 (12) :951-953. [7]WU CX, WANG P, ZHANG CY, et al.Protective mechanism of low dose of triptolide pretreatment against liver ischemia/reperfusion injury in mice[J].Chin J Organ Transplant, 2010, 31 (12) :733-736. (in Chinese) 武传星, 王平, 张传永, 等.低剂量雷公藤甲素预处理减轻小鼠肝脏缺血再灌注损伤的作用及其机制[J].中华器官移植杂志, 2010, 31 (12) :733-736. [8]JIN S, HAN XC.Hepatic ischemia-reperfusion injury[J].J Clin Res, 2005, 22 (3) :397-400. (in Chinese) 金山, 韩喜春.肝缺血再灌注损伤[J].医学临床研究, 2005, 22 (3) :397-400. [9]WANG QQ, ZHAO X, CHEN YC, et al.Research advances in mechanisms and intervention of hepatic ischemia-reperfusion injury[J].J Clin Hepatol, 2016, 32 (6) :1225-1228. (in Chinese) 王清卿, 赵鑫, 陈玉超, 等.肝脏缺血再灌注损伤机制及干预的研究进展[J].临床肝胆病杂志, 2016, 32 (6) :1225-1228. [10]ABU-AMARA M, YANG SY, TAPURIA N, et al.Liver ischemia/reperfusion injury:processes in inf Iammatory networks-areview[J].Liver Transpl, 2010, 16 (9) :1016-1032. [11]KOMATSU H, KOO A, GHADISHAH E, et al.Neutrophil accumulation in ischemic reperfusion rat liver:evidence for a role for superoxide free radicals[J].Am J Physiol, 1992, 2 (62) :669-676. [12]CHEN X, CHENG QP.Clinical effect of Ulinastatin combined with early continuous renal replacement therapy in the treatment of severe acute pancreatitis and its influence on CRP and IL-6[J].China Med Herald, 2017, 14 (23) :122-125. (in Chinese) 陈新, 程起鹏.乌司他丁联合连续性肾脏替代疗法治疗急性重症胰腺炎的临床效果及对CRP、IL-6水平的影响[J].中国医药导报, 2017, 14 (23) :122-125. [13]LENG YX, YANG SG, SONG YH, et al.Ulinastatin for acute lung injury and acute respiratory distress syndrome:a systematic review and meta-analysis[J].World J Crit Care Med, 2014, 3 (1) :34-41. [14]LIU ZC, WANG B, HUA F.Effect of Ulinastatin on serum plasminogen activator inhibitor-1, tissue plasminogen activator in patients with acute lung injury[J].China Med Herald, 2016, 13 (24) :148-151. (in Chinese) 刘志聪, 王斌, 华锋.乌司他丁对急性肺损伤患者血清纤溶酶原激活物抑制剂-1、组织型纤溶酶原激活剂的影响[J].中国医药导报, 2016, 13 (24) :148-151. [15]ZHANG GY, WANG CX, WANG JX, et al.The protective effect of ulinastatin on oxidative stress injury of vascular endothelial cells and its mechanism in vitro[J].Chin J Clin Res, 2016, 29 (2) :193-198. (in Chinese) 张国玉, 王春鲜, 王建星, 等.乌司他丁对血管内皮细胞氧化应激损伤的保护作用及机制[J].中国临床研究, 2016, 29 (2) :193-198. [16]WANG Y, GAO W, QIN XB, et al.Study for the effect of different time ischemic preconditioning and its mechanism on improving hepatic ischemia-reperfusion injury in rats[J].China J Modern Med, 2004, 14 (2) :36-42. (in Chinese) 王野, 高伟, 秦宪斌, 等.探讨不同时间缺血预处理对肝脏缺血再灌注损伤的影响及其机制[J].中国现代医学杂志, 2004, 14 (2) :36-42. [17]SUYAVARAN A, THIRUNAVUKKARASU C.Preconditioning methods in the management of hepatic ischemia reperfusion-induced injury:update on molecular and future perspectives[J].Hepatol Res, 2017, 47 (1) :31-48. [18]FIGUEIRA ER, ROCHA-FILHO JA, NAKATANI M, et al.Hepatic ischemic preconditioning increases portal vein flow in experimental liver ischemia reperfusion injury[J].Hepatobiliary Pancreat Dis Int, 2014, 13 (1) :40-47. [19]FU Z, HUANG S, LI WM, et al.Experimental study on the role of NF-κB in the mechanism of I/R injury and protection of ischemic preconditioning for liver in rats[J/CD].Chin J Clinicians:Electronic Edition, 2013, 7 (13) :5961-5965. (in Chinese) 富智, 黄苏, 李文美, 等.NF-κB在大鼠肝缺血再灌注损伤与缺血预处理保护机制中的作用[J/CD].中华临床医师杂志:电子版, 2013, 7 (13) :5961-5965.
计量
- 文章访问数: 2071
- HTML全文浏览量: 8
- PDF下载量: 434
- 被引次数: 0