Effects of macrophage migration inhibitory factor inhibitor ISO-1 on intestinal injury induced by acute necrotic pancreatitis in pregnant rat model_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YOU Yundong ¹ , ZHAO Liang ^1,2 , MEI Fangchao ^1,2 , HONG Yupu ^1,2 ,  WANG Weixing ¹

1. Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan 430060, P. R. China;

Corresponding author：

WANG Weixing, Email: sate.llite@163.com

Keywords：

acute pancreatitis in pregnancy; intestinal injury; macrophage migration inhibitory factor; nuclear factor-κB; tumor necrosis factor-α

DOI：

10.7507/1007-9424.201805101

Video：

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Objective To explore effects of macrophage migration inhibitory factor (MIF) inhibitor ISO-1 on intestinal injury in acute necrotic pancreatitis in pregnancy (ANPIP) rat. Methods Twenty-four pregnant SD rats were randomly averagely divided into three groups: a sham operation (SO) group, an ANP group, and an ANP model plus ISO-1 treatment group (ISO-1 group). A rat model of ANP was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. The rats were killed and the inferior vena cava blood and the tissues of pancreas and jejunum were harvested at 12 h after the operation. The serum amylase (AMY), lipase (LIP), diamine oxidase (DAO), interleukin (IL)-1β, and IL-6 levels were measured. The pancreatic and jejunal tissues were taken for the pathological examination scoring. The immunohistochemical method was used to detect the expression of the MIF, nuclear factor (NK)-κB, or tumor necrosis factor (TNF)-α protein. Results ① Compared with the SO group, the serum AMY, LIP, DAO, IL-1β, and IL-6 levels were increased in the ANP group (P<0.050), which in the ISO-1 group were decreased as compared with the ANP group, the DAO, IL-1β, and IL-6 levels had significant differences (P<0.050), but the AMY and LIP levels had no significant differences (P>0.050). ② The pathological points of the pancreas and jejunum tissues were increased in the ANP group as compared with the SO group, which were significantly decreased in the ISO-1 group as compared with the ANP group (P<0.050). ③ The average integrated optical density divide by area of the NF-κB,TNF-α, and MIF were significantly increased in the ANP group as compared with the SO group, which were significantly decreased in the ISO-1 group as compared with the ANPgroup (P<0.050). Conclusions MIF inhibitor ISO-1 could protect intestinal injury in ANPIP rat. It is suggested that MIF is one of mechanisms in ANPIP with intestinal injury and might be correlated with activities of TNF-α and NF-κB.

Citation： YOU Yundong, ZHAO Liang, MEI Fangchao, HONG Yupu, WANG Weixing. Effects of macrophage migration inhibitory factor inhibitor ISO-1 on intestinal injury induced by acute necrotic pancreatitis in pregnant rat model. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(11): 1308-1312. doi: 10.7507/1007-9424.201805101 Copy

1.	Sun L, Li W, Sun F, et al. Intra-abdominal pressure in third trimester pregnancy complicated by acute pancreatitis: an observational study. BMC Pregnancy Childbirth, 2015, 15: 223.
2.	Nanda S, Gupta A, Dora A, et al. Acute pancreatitis: a rare cause of acute abdomen in pregnancy. Arch Gynecol Obstet, 2009, 279(4): 577-578.
3.	Cain MA, Ellis J, Vengrove MA, et al. Gallstone and severe hypertriglyceride-induced pancreatitis in pregnancy. Obstet Gynecol Surv, 2015, 70(9): 577-583.
4.	Yu J, Deng W, Wang W, et al. Inhibition of poly (ADP-ribose) polymerase attenuates acute kidney injury in sodium taurocholate-induced acute pancreatitis in rats. Pancreas, 2012, 41(8): 1299-1305.
5.	Schmidt J, Rattner DW, Lewandrowski K, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg, 1992, 215(1): 44-56.
6.	Chiu CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in low-flow states. Ⅰ. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg, 1970, 101(4): 478-483.
7.	Luo L, Zen H, Xu H, et al. Clinical characteristics of acute pancreatitis in pregnancy: experience based on 121 cases. Arch Gynecol Obstet, 2018, 297(2): 333-339.
8.	Hacker FM, Whalen PS, Lee VR, et al. Maternal and fetal outcomes of pancreatitis in pregnancy. Am J Obstet Gynecol, 2015, 213(4): 568. e1-e5.
9.	Robertson KW, Stewart IS, Imrie CW. Severe acute pancreatitis and pregnancy. Pancreatology, 2006, 6(4): 309-315.
10.	Xiong Y, Chen L, Fan L, et al. Free total rhubarb anthraquinones protect intestinal injury via regulation of the intestinal immune response in a rat model of severe acute pancreatitis. Front Pharmacol, 2018, 9: 75.
11.	Calandra T, Bucala R. Macrophage migration inhibitory factor (MIF): A glucocorticoid counter-regulator within the immune system. Crit Rev Immunol, 2017, 37(2-6): 359-370.
12.	Vujicic M, Saksida T, Despotovic S, et al. The role of macrophage migration inhibitory factor in the function of intestinal barrier. Sci Rep, 2018, 8(1): 6337.
13.	Barnes MA, McMullen MR, Roychowdhury S, et al. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology, 2013, 57(5): 1980-1991.
14.	Wu G, Sun Y, Wang K, et al. Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS. Sci Rep, 2016, 6: 30067.
15.	Sparkes A, De Baetselier P, Brys L, et al. Novel half-life extended anti-MIF nanobodies protect against endotoxic shock. FASEB J, 2018, 32(6): 3411-3422.
16.	Kim MJ, Kim WS, Kim DO, et al. Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity. Cell Signal, 2017, 34: 110-120.
17.	Bernhagen J, Calandra T, Cerami A, et al. Macrophage migration inhibitory factor is a neuroendocrine mediator of endotoxaemia. Trends Microbiol, 1994, 2(6): 198-201.
18.	Cao WG, Morin M, Metz C, et al. Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NFkappaB. Biol Reprod, 2005, 73(3): 565-570.
19.	Baker SJ, Reddy EP. Transducers of life and death: TNF receptor superfamily and associated proteins. Oncogene, 1996, 12(1): 1-9.
20.	Martial NT, 洪育蒲, 赵亮, 等. 栗精胺对重症急性胰腺炎大鼠肾脏损伤保护作用的研究. 中国普外基础与临床杂志, 2017, 24(10): 1200-1205.
21.	Mei F, Zuo T, Zhao L, et al. Differential JNK, p38 and ERK response to renal injury in a rat model of acute pancreatitis in pregnancy. Arch Gynecol Obstet, 2018, 297(4): 933-942.
22.	Twait E, Williard DE, Samuel I. Dominant negative p38 mitogen-activated protein kinase expression inhibits NF-kappaB activation in AR42J cells. Pancreatology, 2010, 10(2-3): 119-128.
23.	Yan Y, Lu B, Li P, et al. NOD receptor and TLR9 modulation in severe acute pancreatitis induced intestinal injury. Mol Med Rep, 2017, 16(6): 8471-8476.
24.	Schulte-Michels J, Keksel C, Häberlein H, et al. Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB. Inflammopharmacology, 2018 May 11. doi: 10.1007/s10787-018-0494-9.
25.	Zhou Y, Zhao L, Mei F, et al. Macrophage migration inhibitory factor antagonist (S,R)3 (4 hydroxyphenyl) 4,5 dihydro 5 isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy. Mol Med Rep, 2018, 17(5): 6576-6584.

1. Sun L, Li W, Sun F, et al. Intra-abdominal pressure in third trimester pregnancy complicated by acute pancreatitis: an observational study. BMC Pregnancy Childbirth, 2015, 15: 223.
2. Nanda S, Gupta A, Dora A, et al. Acute pancreatitis: a rare cause of acute abdomen in pregnancy. Arch Gynecol Obstet, 2009, 279(4): 577-578.
3. Cain MA, Ellis J, Vengrove MA, et al. Gallstone and severe hypertriglyceride-induced pancreatitis in pregnancy. Obstet Gynecol Surv, 2015, 70(9): 577-583.
4. Yu J, Deng W, Wang W, et al. Inhibition of poly (ADP-ribose) polymerase attenuates acute kidney injury in sodium taurocholate-induced acute pancreatitis in rats. Pancreas, 2012, 41(8): 1299-1305.
5. Schmidt J, Rattner DW, Lewandrowski K, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg, 1992, 215(1): 44-56.
6. Chiu CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in low-flow states. Ⅰ. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg, 1970, 101(4): 478-483.
7. Luo L, Zen H, Xu H, et al. Clinical characteristics of acute pancreatitis in pregnancy: experience based on 121 cases. Arch Gynecol Obstet, 2018, 297(2): 333-339.
8. Hacker FM, Whalen PS, Lee VR, et al. Maternal and fetal outcomes of pancreatitis in pregnancy. Am J Obstet Gynecol, 2015, 213(4): 568. e1-e5.
9. Robertson KW, Stewart IS, Imrie CW. Severe acute pancreatitis and pregnancy. Pancreatology, 2006, 6(4): 309-315.
10. Xiong Y, Chen L, Fan L, et al. Free total rhubarb anthraquinones protect intestinal injury via regulation of the intestinal immune response in a rat model of severe acute pancreatitis. Front Pharmacol, 2018, 9: 75.
11. Calandra T, Bucala R. Macrophage migration inhibitory factor (MIF): A glucocorticoid counter-regulator within the immune system. Crit Rev Immunol, 2017, 37(2-6): 359-370.
12. Vujicic M, Saksida T, Despotovic S, et al. The role of macrophage migration inhibitory factor in the function of intestinal barrier. Sci Rep, 2018, 8(1): 6337.
13. Barnes MA, McMullen MR, Roychowdhury S, et al. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology, 2013, 57(5): 1980-1991.
14. Wu G, Sun Y, Wang K, et al. Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS. Sci Rep, 2016, 6: 30067.
15. Sparkes A, De Baetselier P, Brys L, et al. Novel half-life extended anti-MIF nanobodies protect against endotoxic shock. FASEB J, 2018, 32(6): 3411-3422.
16. Kim MJ, Kim WS, Kim DO, et al. Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity. Cell Signal, 2017, 34: 110-120.
17. Bernhagen J, Calandra T, Cerami A, et al. Macrophage migration inhibitory factor is a neuroendocrine mediator of endotoxaemia. Trends Microbiol, 1994, 2(6): 198-201.
18. Cao WG, Morin M, Metz C, et al. Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NFkappaB. Biol Reprod, 2005, 73(3): 565-570.
19. Baker SJ, Reddy EP. Transducers of life and death: TNF receptor superfamily and associated proteins. Oncogene, 1996, 12(1): 1-9.
20. Martial NT, 洪育蒲, 赵亮, 等. 栗精胺对重症急性胰腺炎大鼠肾脏损伤保护作用的研究. 中国普外基础与临床杂志, 2017, 24(10): 1200-1205.
21. Mei F, Zuo T, Zhao L, et al. Differential JNK, p38 and ERK response to renal injury in a rat model of acute pancreatitis in pregnancy. Arch Gynecol Obstet, 2018, 297(4): 933-942.
22. Twait E, Williard DE, Samuel I. Dominant negative p38 mitogen-activated protein kinase expression inhibits NF-kappaB activation in AR42J cells. Pancreatology, 2010, 10(2-3): 119-128.
23. Yan Y, Lu B, Li P, et al. NOD receptor and TLR9 modulation in severe acute pancreatitis induced intestinal injury. Mol Med Rep, 2017, 16(6): 8471-8476.
24. Schulte-Michels J, Keksel C, Häberlein H, et al. Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB. Inflammopharmacology, 2018 May 11. doi: 10.1007/s10787-018-0494-9.
25. Zhou Y, Zhao L, Mei F, et al. Macrophage migration inhibitory factor antagonist (S,R)3 (4 hydroxyphenyl) 4,5 dihydro 5 isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy. Mol Med Rep, 2018, 17(5): 6576-6584.

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Effects of macrophage migration inhibitory factor inhibitor ISO-1 on intestinal injury induced by acute necrotic pancreatitis in pregnant rat model

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