Protective effect of PPAR-β on liver injury in sepsis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Nana ¹ , ZHANG Xinyu ¹ , YANG Wei ¹ , MENG Xianglin ¹ , ZHAO Mingyan ¹ , YU Kaijiang ¹ , LIU Wei ² ,  KANG Kai ¹

1. Department of Intensive Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;
2. Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;

Corresponding author：

KANG Kai, Email: janekk79@126.com

Keywords：

sepsis-induced liver injury; peroxisome proliferator-activated receptor-beta; review

DOI：

10.7507/1007-9424.201904044

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the protective effect of peroxisome proliferator-activated receptor-beta (PPAR-β) in sepsis-induced liver injury and the mechanism, and to provide new ideas for the prevention and treatment of sepsis-induced liver injury.Method Relevant literatures about protective effect of PPAR-β in sepsis-induced liver injury were collected and reviewed.Results PPAR-β played an important role in cell survival, anti-inflammatory, and anti-oxidation. It acted on a variety of pathophysiological processes, could reduce the activation of inflammatory factors, reduce the production of oxygen free radicals, and inhibit the expression of apoptotic proteins, as well as played an important role in anti-inflammatory, anti-oxidative, and anti-apoptotic.Conclusion PPAR-β can inhibit the activation of NF-κB, reduce the release of inflammatory factors, reduce apoptosis, and reduce liver injury by antioxidation, thereby reducing the mortality of sepsis-induced liver injury.

Citation： LI Nana, ZHANG Xinyu, YANG Wei, MENG Xianglin, ZHAO Mingyan, YU Kaijiang, LIU Wei, KANG Kai. Protective effect of PPAR-β on liver injury in sepsis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(12): 1495-1499. doi: 10.7507/1007-9424.201904044 Copy

1.	Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med, 2018, 46(6): 997-1000.
2.	Finney SJ, Leaver SK, Evans TW, et al. Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression. Intensive Care Med, 2012, 38(2): 324-332.
3.	邢小康, 李曼, 郭丰. 脓毒症相关肝损伤分析. 中国继续医学教育, 2018, 10(27): 87-88.
4.	潘毅, 何飞民, 程英, 等. 脓毒症患者并发急性肝损伤的危险因素分析. 当代医学, 2017, 23(26): 80-82.
5.	Fuhrmann V, Kneidinger N, Herkner H, et al. Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med, 2011, 37(8): 1302-1310.
6.	沈桂佳, 安鹏, 聂玉强, 等. PPAR-β/δ及其激动剂L165041对小鼠肝脏成瘤的影响. 胃肠病学和肝病学杂志, 2015, 24(11): 1350-1353.
7.	Nastos C, Kalimeris K, Papoutsidakis N, et al. Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev, 2014, 2014: 906965.
8.	王晓琴. 脓毒症肝功能障碍发病机制的研究进展. 中国急救医学, 2016, 36(3): 224-228.
9.	周锦平, 周立新. 脓毒症休克的早期目标液体管理的研究进展. 当代医学, 2016, 22(11): 11-13.
10.	孙宁. 脓毒症合并肝损伤的诊断与治疗研究进展. 中国临床新医学, 2018, 11(3): 294-298.
11.	吴春华, 杜伟, 余义俊, 等. 兔VX2肝癌经导管动脉栓塞术后癌旁肝组织氧化应激及细胞凋亡. 中国介入影像与治疗学, 2019, 16(2): 112-116.
12.	Chen Z, Eadie AL, Hall SR, et al. Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements. Front Biosci (Schol Ed), 2017, 9: 46-54.
13.	王伟, 郝守艳, 徐紫薇, 等. 老年患者脓毒症心肌病临床诊治. 中国老年学杂志, 2019, 39(5): 1262-1265.
14.	Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature, 2013, 496(7446): 445-455.
15.	邢志祥, 沈世强. 重症急性胰腺炎肝损伤的研究进展. 腹部外科, 2016, 29(6): 478-481, 485.
16.	Farghali H, Kgalalelo Kemelo M, Wojnarová L, et al. In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs. Physiol Res, 2016, 65(Supplementum 4): S417-S425.
17.	李万平, 李晓冰, 黄新武, 等. 灵芪蠲肝液对急性肝损伤内毒素和氧自由基的作用. 时珍国医国药, 2008, 19(3): 657-658.
18.	Lorente L, Martín MM, Abreu-González P, et al. Prognostic value of malondialdehyde serum levels in severe sepsis: a multicenter study. PLoS One, 2013, 8(1): e53741.
19.	Kim SJ, Park JS, Lee DW, et al. Trichostatin a protects liver against septic injury through inhibiting Toll-like receptor signaling. Biomol Ther (Seoul), 2016, 24(4): 387-394.
20.	夏婷, 张瑾, 姚佳慧, 等. 氧化应激在酒精性肝病中作用机制的研究进展. 中国药理学通报, 2017, 33(10): 1353-1356.
21.	Papakonstantinou VD, Lagopati N, Tsilibary EC, et al. A review on platelet activating factor inhibitors: could a new class of potent metal-based anti-inflammatory drugs induce anticancer properties? Bioinorg Chem Appl, 2017, 2017: 6947034.
22.	Moschos MM, Nitoda E, Chatziralli IP, et al. Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study. Drug Des Devel Ther, 2016, 10: 3977-3981.
23.	余胜华, 吕志宝. 血小板活化因子在新生儿坏死性小肠结肠炎发病中的作用. 中华小儿外科杂志, 2017, 38(6): 475-479.
24.	Monsalve FA, Pyarasani RD, Delgado-Lopez F, et al. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm, 2013, 2013: 549627.
25.	Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab, 2012, 23(7): 351-363.
26.	Xu M, Zuo X, Shureiqi I. Targeting peroxisome proliferator-activated receptor-β/δ in colon cancer: how to aim? Biochem Pharmacol, 2013, 85(5): 607-611.
27.	Mirza AZ, Althagafi II, Shamshad H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur J Med Chem, 2019, 166: 502-513.
28.	de Bilbao F, Arsenijevic D, Moll T, et al. In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem, 2009, 110(1): 12-22.
29.	Murakami T, Ockinger J, Yu J, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A, 2012, 109(28): 11282-11287.
30.	Flood PM, Qian L, Peterson LJ, et al. Transcriptional factor NF-κB as a target for therapy in parkinson’s disease. Parkinsons Dis, 2011, 2011: 216298.
31.	Arcipowski KM, Stunz LL, Bishop GA. TRAF6 is a critical regulator of LMP1 functions in vivo. Int Immunol, 2014, 26(3): 149-158.
32.	Lee MY, Choi R, Kim HM, et al. Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism. Exp Mol Med, 2012, 44(10): 578-585.
33.	Naidenow J, Hrgovic I, Doll M, et al. Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells. J Inflamm (Lond), 2016, 13(1): 27.
34.	Li Y, Guo Y, Chen Y, et al. Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone ⅡA on atherosclerosis. Mol Med Rep, 2015, 12(2): 1665-1676.
35.	Chao X, Xiong C, Dong W, et al. Activation of peroxisome proliferator-activated receptor β/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats. J Stroke Cerebrovasc Dis, 2014, 23(6): 1396-1402.
36.	Djafarzadeh S, Vuda M, Takala J, et al. Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes. PLoS One, 2012, 7(9): e45195.
37.	Romanowska M, Reilly L, Palmer CN, et al. Activation of PPARbeta/delta causes a psoriasis-like skin disease in vivo. PLoS One, 2010, 5(3): e9701.
38.	Letavernier E, Perez J, Joye E, et al. Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure. J Am Soc Nephrol, 2005, 16(8): 2395-2402.
39.	Sertznig P, Seifert M, Tilgen W, et al. Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. J Cell Physiol, 2007, 212(1): 1-12.
40.	Khazaei M, Salehi E, Rashidi B, et al. Role of peroxisome proliferator-activated receptor β agonist on angiogenesis in hindlimb ischemic diabetic rats. J Diabetes Complications, 2012, 26(2): 137-140.
41.	Minutoli L, Antonuccio P, Polito F, et al. Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury. J Urol, 2009, 181(4): 1913-1921.
42.	Fan Y, Wang Y, Tang Z, et al. Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells. Arterioscler Thromb Vasc Biol, 2008, 28(2): 315-321.
43.	Benetti E, Patel NS, Collino M. The role of PPARβ/δ in the management of metabolic syndrome and its associated cardiovascular complications. Endocr Metab Immune Disord Drug Targets, 2011, 11(4): 273-284.

1. Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med, 2018, 46(6): 997-1000.
2. Finney SJ, Leaver SK, Evans TW, et al. Differences in lipopolysaccharide- and lipoteichoic acid-induced cytokine/chemokine expression. Intensive Care Med, 2012, 38(2): 324-332.
3. 邢小康, 李曼, 郭丰. 脓毒症相关肝损伤分析. 中国继续医学教育, 2018, 10(27): 87-88.
4. 潘毅, 何飞民, 程英, 等. 脓毒症患者并发急性肝损伤的危险因素分析. 当代医学, 2017, 23(26): 80-82.
5. Fuhrmann V, Kneidinger N, Herkner H, et al. Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med, 2011, 37(8): 1302-1310.
6. 沈桂佳, 安鹏, 聂玉强, 等. PPAR-β/δ及其激动剂L165041对小鼠肝脏成瘤的影响. 胃肠病学和肝病学杂志, 2015, 24(11): 1350-1353.
7. Nastos C, Kalimeris K, Papoutsidakis N, et al. Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev, 2014, 2014: 906965.
8. 王晓琴. 脓毒症肝功能障碍发病机制的研究进展. 中国急救医学, 2016, 36(3): 224-228.
9. 周锦平, 周立新. 脓毒症休克的早期目标液体管理的研究进展. 当代医学, 2016, 22(11): 11-13.
10. 孙宁. 脓毒症合并肝损伤的诊断与治疗研究进展. 中国临床新医学, 2018, 11(3): 294-298.
11. 吴春华, 杜伟, 余义俊, 等. 兔VX2肝癌经导管动脉栓塞术后癌旁肝组织氧化应激及细胞凋亡. 中国介入影像与治疗学, 2019, 16(2): 112-116.
12. Chen Z, Eadie AL, Hall SR, et al. Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements. Front Biosci (Schol Ed), 2017, 9: 46-54.
13. 王伟, 郝守艳, 徐紫薇, 等. 老年患者脓毒症心肌病临床诊治. 中国老年学杂志, 2019, 39(5): 1262-1265.
14. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature, 2013, 496(7446): 445-455.
15. 邢志祥, 沈世强. 重症急性胰腺炎肝损伤的研究进展. 腹部外科, 2016, 29(6): 478-481, 485.
16. Farghali H, Kgalalelo Kemelo M, Wojnarová L, et al. In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs. Physiol Res, 2016, 65(Supplementum 4): S417-S425.
17. 李万平, 李晓冰, 黄新武, 等. 灵芪蠲肝液对急性肝损伤内毒素和氧自由基的作用. 时珍国医国药, 2008, 19(3): 657-658.
18. Lorente L, Martín MM, Abreu-González P, et al. Prognostic value of malondialdehyde serum levels in severe sepsis: a multicenter study. PLoS One, 2013, 8(1): e53741.
19. Kim SJ, Park JS, Lee DW, et al. Trichostatin a protects liver against septic injury through inhibiting Toll-like receptor signaling. Biomol Ther (Seoul), 2016, 24(4): 387-394.
20. 夏婷, 张瑾, 姚佳慧, 等. 氧化应激在酒精性肝病中作用机制的研究进展. 中国药理学通报, 2017, 33(10): 1353-1356.
21. Papakonstantinou VD, Lagopati N, Tsilibary EC, et al. A review on platelet activating factor inhibitors: could a new class of potent metal-based anti-inflammatory drugs induce anticancer properties? Bioinorg Chem Appl, 2017, 2017: 6947034.
22. Moschos MM, Nitoda E, Chatziralli IP, et al. Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study. Drug Des Devel Ther, 2016, 10: 3977-3981.
23. 余胜华, 吕志宝. 血小板活化因子在新生儿坏死性小肠结肠炎发病中的作用. 中华小儿外科杂志, 2017, 38(6): 475-479.
24. Monsalve FA, Pyarasani RD, Delgado-Lopez F, et al. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm, 2013, 2013: 549627.
25. Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab, 2012, 23(7): 351-363.
26. Xu M, Zuo X, Shureiqi I. Targeting peroxisome proliferator-activated receptor-β/δ in colon cancer: how to aim? Biochem Pharmacol, 2013, 85(5): 607-611.
27. Mirza AZ, Althagafi II, Shamshad H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. Eur J Med Chem, 2019, 166: 502-513.
28. de Bilbao F, Arsenijevic D, Moll T, et al. In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice. J Neurochem, 2009, 110(1): 12-22.
29. Murakami T, Ockinger J, Yu J, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A, 2012, 109(28): 11282-11287.
30. Flood PM, Qian L, Peterson LJ, et al. Transcriptional factor NF-κB as a target for therapy in parkinson’s disease. Parkinsons Dis, 2011, 2011: 216298.
31. Arcipowski KM, Stunz LL, Bishop GA. TRAF6 is a critical regulator of LMP1 functions in vivo. Int Immunol, 2014, 26(3): 149-158.
32. Lee MY, Choi R, Kim HM, et al. Peroxisome proliferator-activated receptor δ agonist attenuates hepatic steatosis by anti-inflammatory mechanism. Exp Mol Med, 2012, 44(10): 578-585.
33. Naidenow J, Hrgovic I, Doll M, et al. Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells. J Inflamm (Lond), 2016, 13(1): 27.
34. Li Y, Guo Y, Chen Y, et al. Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone ⅡA on atherosclerosis. Mol Med Rep, 2015, 12(2): 1665-1676.
35. Chao X, Xiong C, Dong W, et al. Activation of peroxisome proliferator-activated receptor β/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats. J Stroke Cerebrovasc Dis, 2014, 23(6): 1396-1402.
36. Djafarzadeh S, Vuda M, Takala J, et al. Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes. PLoS One, 2012, 7(9): e45195.
37. Romanowska M, Reilly L, Palmer CN, et al. Activation of PPARbeta/delta causes a psoriasis-like skin disease in vivo. PLoS One, 2010, 5(3): e9701.
38. Letavernier E, Perez J, Joye E, et al. Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure. J Am Soc Nephrol, 2005, 16(8): 2395-2402.
39. Sertznig P, Seifert M, Tilgen W, et al. Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. J Cell Physiol, 2007, 212(1): 1-12.
40. Khazaei M, Salehi E, Rashidi B, et al. Role of peroxisome proliferator-activated receptor β agonist on angiogenesis in hindlimb ischemic diabetic rats. J Diabetes Complications, 2012, 26(2): 137-140.
41. Minutoli L, Antonuccio P, Polito F, et al. Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury. J Urol, 2009, 181(4): 1913-1921.
42. Fan Y, Wang Y, Tang Z, et al. Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells. Arterioscler Thromb Vasc Biol, 2008, 28(2): 315-321.
43. Benetti E, Patel NS, Collino M. The role of PPARβ/δ in the management of metabolic syndrome and its associated cardiovascular complications. Endocr Metab Immune Disord Drug Targets, 2011, 11(4): 273-284.

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