Objective  To study the protective effect and possible mechanism of peritoneal resusci-tation with pyruvate peritoneal dialysate on renal ischemia reperfusion injury after hemorrhagic shock resuscitation in rats. 

Methods  40 rats were randomly divided into four groups: sham operation group (sham group), intravenous resuscitation group (VR group), normal saline peritoneal resuscitation group (NR group), pyruvate peritoneal dialysis fluid peritoneal resuscitation group (PR group). The rat model of hemorrhagic shock was performed on VR, NR and PR groups. In the sham group, right common carot-id artery, left femoral artery and right femoral vein were punctured and heparinized. Blood and kidney tissues were collected from all groups 24 hours after resuscitation. Serum creatinine and urea nitrogen concentrations were detected by hematology analyzer. Renal histopathological results were observed by HE staining and Paller score was performed. The levels of IL-1β and TNF-α were detected by ELISA. The expression levels of p-STAT3 and p-JAK2 were determined by Western blot. 

Results  Compared with sham group, the renal tubular Paller score, serum creatinine and urea nitrogen levels in VR, NR and PR groups were increased, the contents of IL-1 β, TNF-α and the expressions of p-STAT3 and p-JAK2 were increased (P<0.05). Compared with VR and NR groups, the renal tubular Paller score, serum creatinine and urea nitrogen levels were decreased, the contents of IL-1β, TNF-α and the expressions of p-STAT3 and p-JAK2 were decreased in PR group (P<0.05). 

Conclusion  Pyruvate peritoneal dialysate peritone-al resuscitation can reduce renal ischemia reperfusion injury and improve renal function after hemor-rhagic shock resuscitation. The mechanism may be related to reducing inflammatory response and in-hibiting the activation of JAK2 / STAT3 signaling pathway.

1.Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline[J]. Crit Care, 2013, 17(2): R76. DOI: 10.1186/cc12685.

2.Iñiguez M, Dotor J, Feijoo E, et al. Novel pharmacologic strategies to protect the liver from ischemia-reperfusion injury[J]. Recent Pat Cardiovasc Drug Discov, 2008, 3(1): 9-18. DOI: 10.2174/157489008783331643.

3.Mayeur N, Minville V, Jaafar A, et al. Morphologic and functional renal impact of acute kidney injury after prolonged hemorrhagic shock in mice[J]. Crit Care Med, 2011, 39(9): 2131-2138. DOI: 10.1097/CCM.0b013 e31821f04f0.

4.Santry HP, Alam HB. Fluid resuscitation: past, present, and the future[J]. Shock, 2010, 33(3): 229-241. DOI: 10.1097/SHK.0b013e3181c30f0c.

5.Garrison RN, Conn AA, Harris PD, et al. Direct peritoneal resuscitation as adjunct to conven-tional resuscitation from hemorrhagic shock: a better outcome[J]. Surgery, 2004, 136(4): 900-908. DOI: 10.1016/j.surg.2004.06.027.

6.Zakaria el R, Hurt RT, Matheson PJ, et al. A novel method of peritoneal resuscitation im-proves organ perfusion after hemorrhagic shock[J]. Am J Surg, 2003, 186(5): 443-448. DOI: 10.1016/j.amjsurg.2003.07.006.

7.Dai ZL, Wu J, Meng C, et al. Ringer's malate solution protects against the multiple organ injury and dysfunction caused by hemorrhagic shock in rats[J]. Shock, 2012, 38(3): 268-274. DOI: 10.1097/SHK.0b013e318264e664.

8.Blaisdell FW. The reperfusion syndrome[J]. Microcirc Endothelium Lymphatics, 1989, 5(3-5): 127-141.

9.Tanaka N. Induction mechanism of shock: applying the etiology in judgment of the cause of death in forensic practice[J]. Nihon Hoigaku Zasshi, 2004, 58(2): 130-140. DOI: mdl-15526767.

10.Zhang X, Darnell JE Jr. Functional importance of stat3 tetramerization in activation of the alpha 2-macroglobulin gene[J]. J Biol Chem, 2001, 276(36): 33576-33581. DOI: 10.1074/jbc.M104978200.

11.Lee C, Lim HK, Sakong J, et al. Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin (IL)-1β and IL-6 production[J]. Mol Pharmacology, 2006, 69(3): 1041-1047. DOI: 10.1124/mol.105.018481.

12.冯欣, 李垚, 王雪鹰. JAK/STAT通路在大鼠肾脏缺血再灌注损伤中的作用[J]. 解放军医学杂志, 2011, 36(3): 218-220. [Feng X, Li Y, Wang XY. Effect of JAK/STAT pathway on renal ische-mia-reperfusion injury in rats[J]. Medical Journal of Chinese People's Liberation Army, 2011, 36(3): 218-220.] DOI: CNKI:SUN:JFJY.0.2011-03-006.

13.Fink MP. The therapeutic potential of pyruvate[J]. J Surg Res, 2010, 164(2): 218-220. DOI: 10.1016/j.jss.2010.01. 046.

14.Wiggers HC, Ingraham RC. Hemorrhagic shock：definition and criteria for its diagnosis[J]. J Clin Invest, 1946, 25(1): 30-36. DOI: 10.1172/JCI101686.

15.余晓东, 廖波, 邓显忠, 等. 一种新型实用的大鼠肾缺血再灌注损伤模型的建立[J]. 重庆医学, 2011, 40(13): 1283-1284. [Yu XD, Liao B, Deng XZ, et al. Model construction of renal ische-mia-reperfusion injury in rats[J]. Chongqing Medicine, 2011, 40(13): 1283-1284.] DOI: 10.3969/j.issn.1671-8348.2011.13.014.

16.Paller MS, Hoidal JR, Ferris TF. Oxygen free radicals in ischemic acute renal failure in the rat[J]. J Clin Invest, 1984, 74(4): 1156-1164. DOI: 10.1172/JCI111524.

17.Sordi R, Chiazza F, Johnson FL, et al. Inhibition of iκb kinase attenuates the organ injury and dysfunction associated with hemorrhagic shock[J]. Mol Med, 2015, 21(1): 563-575. DOI: 10.2119/molmed.2015.00049.

18.Rhee P, Koustova E, Alam HB. Searching for the optimal resuscitation method: recom-mendations for the initial fluid resuscitation of combat casualties[J]. J Trauma, 2003, 54(5): 52-62. DOI: 10.1097/01.TA.0000064507.80390.10.

19.黄霖, 廖盼丽, 张炯. 莱菔硫烷激动Nrf-2抗炎症改善小鼠肾缺血再灌注损伤[J]. 西安交通大学学报(医学版), 2019, 40(5): 696-701. [Huang L, Liao PL, Zhang J. Sulforaphane attenuates renal is-chemia reperfusion injury in mice by Nrf-2 against inflammation[J]. Journal of Xi'an Jiao-tong University (Medical Sciences), 2019, 40(5): 696-701.] DOI: 10.7652/jdyxb201905006.

20.孙贺元, 张增光, 阎渭清,等. 地塞米松对缺血再灌注大鼠肾损伤的保护作用及其机制[J]. 中华实验外科杂志, 2019, 36(11): 2075-2077. [Sun HY, Zhang ZG, Yan WQ, et al. Mechanism and protec-tive effect of dexamethasone on renal injury induced by ischemia-reperfusion in rats[J]. Chinese Journal of Experimental Surgery, 2019, 36(11): 2075-2077.] DOI: 10.3760/cma.j.issn.1001-9030.2019.11.046.

21.Tan F, Chen Y, Yuan D, et al. Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats[J]. Biomed Rep, 2015, 3(3): 365-370. DOI: 10.3892/br.2015.427.

22.Fu C, Dai X, Yang Y, et al. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats[J]. Mol Med Rep, 2017, 15(1): 131-138. DOI: 10.3892/mmr.2016.6012.

23.沈诚, 范士志, 陈建明, 等. JAK/STAT通路对缺血再灌注心肌NF-kB和Caspase-3表达的影响[J]. 中国误诊学杂志, 2006, 6(1): 6-8. [Shen C, Fan SZ, Chen JM, et al. The roles of janus ki-nase/signal transducer and activator of transcription pathway in mediating levels of NF-kB and caspase-3 during ischemia-reperfusion in rat cardiac muscles[J]. Chinese Journal of Misdiagnostics, 2006, 6(1): 6-8.] DOI: 10.3969/j.issn.1009-6647.2006.01.003.

24.任晓芬, 韩毅, 赵晓英, 等. 辣椒素减轻大鼠肾缺血-再灌注损伤的作用[J]. 临床麻醉学杂志, 2019, 35(4): 384-388. [Ren XF, Han Y, Zhao XY, et al. Effect of capsaicin on renal ische-mia-reperfusion injury in rats[J]. Journal of Clinical Anesthesiology, 2019, 35(4): 384-388.] DOI: 10.12089/jca.2019.04.018.

25.Lu TC, Wang ZH, Feng X, et al. Knockdown of Stat3 activity in vivo prevents diabetic glo-merulopathy[J]. Kidney Int, 2009, 76(1): 63-71. DOI: 10.1038/ki.2009.98.

26.邓江涛, 张婧婧, 沈会琴, 等. 丙酮酸盐腹腔复苏对失血性休克大鼠肠组织JAK/STAT信号通路的影响[J]. 中华麻醉学杂志, 2019, 39(7): 866-869. [Deng JT, Zhang JJ, Shen HQ, et al. Effect of py-ruvate peritoneal resuscitation on JAK/STAT signaling pathway in intestinal tissues of rats with hemorrhagic shock[J]. Chinese Journal of Anesthesiology, 2019, 39(7): 866-869.] DOI: 10.3760/cma.j.issn.0254-1416.2019.07.025.