Abstract:【Objective】To investigate the expression of HMGB1/RAGE in hepatic ischemia-reperfusion injury (HIRI) and the preconditioning effect of octreotide (Oct) in rats.【Methods】Seventy-two healthy adult male SD rats were randomly divided into three groups equally (n=24): sham operation group(group S), ischemia reperfusion group (group I/R), and octreotide group(group Oct). 30 minutes before operation, the Group Oct received intraperitoneal injection of saline containing Oct 0.25 mg/kg, while the group S and the group I/R were intraperitoneally injected with the same amount of normal saline. HIRI model was established by Pringle 's maneuver method. Blood sampling was collected to detect serum alanine transaminase (ALT) and the change of high mobility group box protein 1 (HMGB1) by immunohistochemistry at liver ischemia 30 min (T1), reperfusion time was 1 h (T2), 6 h (T3) and 12 h (T4). The liver tissue was taken at 12 h after reperfusion, the expression of HMGB1 was detected by immunohistochemistry; The expression of mRNA and protein levels of HMGB1 and advanced glycation end products receptor (RAGE) were detected by real-time quantitative PCR and Western blot respectively.【Results】Serum ALT levels increased from T1 to T4 in the group I/R and the group Oct, all of them were higher than those in the group S, the I/R group was significantly higher than the Oct group, the difference was statistically significant (P<0.05); The level of HMGB1 increased from T1 to T3, T3 peaked and T4 began to decrease, but all were higher than those in group S. The I/R group was significantly higher than the Oct group, the difference was statistically significant (P<0.05). The HMGB1 positive cells showed the cytoplasm of nucleus and cytoplasm were brownish yellow. The positive expression of group I/R and group Oct were (6.8 ± 1.2), (4.1 ±1.5), significantly higher than that of group S (3.2 ± 1.3), and the I/R group was significantly higher than the Oct group, the difference was statistically significant (P<0.05). Compared with group S, the expression of HMGB1, RAGE, mRNA and protein in I/R liver tissue increased significantly (P<0.05); Compared with group I/R, the expression of HMGB1, RAGE and mRNA in Oct group decreased significantly after pretreatment with Oct (P<0.05).【Conclusion】Oct preconditioning has obvious protective effect on HIRI in rats, which may be related to the inhibition of the expression of HMGB1 and RAGE.
孙辉平,杨金凤,邹双发,张秦雅,彭艳华,肖卫强. HMGB1/RAGE在肝缺血再灌注大鼠的表达及奥曲肽的预处理作用[J]. 医学临床研究, 2017, 34(9): 1677-1680.
SUN Hui-ping, YANG Jin-feng, ZOU Shuang-fa,et al. Expression of HMGB1/RAGE in Hepatic Ischemia-reperfusion Injury (HIRI) and the Preconditioning Effect of Octreotide in Rats. JOURNAL OF CLINICAL RESEARCH, 2017, 34(9): 1677-1680.
[1]Tong Y,Tang Z,Yang T,et al.Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition[J].Int J Med Sci,2014,11(4): 337-343. [2]Sims GP.HMGB1 and RAGE in inflammation and cancer[J].Annu Rev Immunol,2010,28:367-388. [3]Tsung A,Sahai R,Tanaka H,et al.The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion[J].J Exp Med,2005,201(7): 1135-1143. [4]Yamamoto T,Ono T,Ito T,et al.Hemoperfusion with a high -mobility group box 1 adsorption column can prevent the occurrence of hepatic ischemia- reperfusion injury in rats[J].Crit Care Med,2010,38(3): 879-885. [5]李杰群.奥曲肽对肝脏热缺血再灌注损伤的保护作用[J].中南大学学报(医学版),2006 ,31(5):792-796. [6]Wang J,Sun Z,Shen J,et al.Octreotide protects the mouse retina against ischemic reperfusion injury through regulation of antioxidation and activation of NF-κB[J].Oxid Med Cell Longev,2015,2015:970156. [7]Takano T,Yonemitsu Y,Saito S,et al.A somatostatin analogue,octreotide,ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygennase-1[J].J Surg Res,2012,175(2):350-358. [8]Yang JF,Sun HP,Takacs P,et al.The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit model[J].Transplant Proc,2013,45(6): 2433-2438. [9]孙辉平,董长生,刘卫珍,等.奥曲肽对兔肝缺血再灌后小肠超微结构、细胞因子、氧自由基的影响[J].医学临床研究,2011,28(1):13-16. [10]Patel YC.Somatostatin and its receptor family[J].Front Neuroendocrinol,1999,20(3):157-198. [11]Chen L,Wang L,Zhang X,et al.The protection by octreotide against experimental ischemic stroke: up-regulated transcription factor Nrf2,HO-1 and down-regulated NF-κB expression[J].Brain Res,2012,1475:80-87. [12]钦丹萍 , 魏霞 , 方国栋,等.全程应用大承气汤加味方对重症急性胰腺炎模型大鼠肠黏膜屏障的影响[J].中国中西结合杂志,2015 ,35(12):1482-1489. [13]张秦雅,杨金凤.HMGB1与肝缺血再灌注损伤相关性的研究进展[J].临床与病理杂志.2016,36(3):303-307.