Experimental study of interferon-γ in preventing intestinal adhesion following abdominal surgery in rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Shengbi ¹ , LI Xiangtao ¹ , ZHOU Jinhong ² , ZHAO Qi ² ,  WENG Qifang ³

1. Grade 2014 Clinical Medicine, Hainan Medical College, Haikou 571199, P. R. China;
2. Grade 2015 Clinical Medicine, Hainan Medical College, Haikou 571199, P. R. China;
3. Department of Physiology, Hainan Medical College, Haikou 571199, P. R. China;

Corresponding author：

WENG Qifang, Email: 33201109@qq.com

Keywords：

interferon γ; fibroblast; interleukin 13; intestinal adhesion

DOI：

10.7507/1007-9424.201810011

Video：

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Objective To observe effect of interferon-γ in preventing intestinal adhesion following abdominal surgery in rats.Methods A total of 60 Wistar rats were selected, which were randomly divided into a sham operation (SO) group, model group, dexamethasone (DXMS) group, and interferon-γ group, then the interferon-γ group was randomly divided into a low, medium, and high concentrations subgroups. Except for the SO group, the laparotomies with file friction caecum were performed for all the other groups to establish the intestinal adhesion model. SO group and model group were intraperitoneally injected with saline for 4 mL/kg. The 10 mg/kg dexamethasone was injected into the abdominal cavity of rats in the DXMS group. The 7.5×10⁴, 1.5×10⁵, and 3.0×10⁵ U/kg interferon-γ concentrations were injected into the abdominal cavity of rats in the low, medium, and high concentrations subgroups respectively. The Nair grading of cecum adhesion degree was assessed on the 8th day after the surgery, then the histopathological change was observed by the HE staining under the microscopy and the hydroxyproline content in the cecum tissue was detected.Results ① The intestinal adhesion: Compared with the SO group, the intestinal adhesions occurred in all the other groups and the degrees of intestinal adhesions evaluated by the Nair grading were more significantly serious (P<0.05), which in the DXMS group and the medium and high concentrations of interferon-γ subgroups were significantly reduced (P<0.05) as compared with the model group, which in the high concentration of interferon-γ subgroup was significantly reduced (P<0.05) as compared with the DXMS group. ② The microscopic observation of histopathological results: Compared with the DXMS group, the high concentration of interferon-γ could effectively reduce the occurrence of fibrous tissue and inflammatory cell infiltration, the intestinal wall muscular layer structure was complete, a few inflammatory cells scattered in the infiltration. ③ The hydroxyproline content: The contents of hydroxyproline in the cecum tissue of the model group, DXMS group, and interferon-γ subgroups were significantly increased (P<0.05) as compared with the SO group, which of the DXMS group and medium and high concentrations of interferon-γ subgroups were significantly decreased (P<0.05) as compared with the model group, which of the high concentration of interferon-γ subgroup was significantly decreased (P<0.05) as compared with the DXMS group.Conclusion Interferon-γ has a preventive and therapeutic effect on postoperative intestinal adhesion and cecum injuries.

Citation： LI Shengbi, LI Xiangtao, ZHOU Jinhong, ZHAO Qi, WENG Qifang. Experimental study of interferon-γ in preventing intestinal adhesion following abdominal surgery in rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(1): 19-24. doi: 10.7507/1007-9424.201810011 Copy

1.	刘国涛, 陈巧, 金丽明, 等. 丹参多酚酸盐联合聚维酮碘预防大鼠术后肠粘连. 浙江中西医结合杂志, 2015, 25(6): 538-541.
2.	Bianchi E, Boekelheide K, Sigman M, et al. Ghrelin inhibits post-operative adhesions via blockage of the TGF-β signaling pathway. PLoS One, 2016, 11(4): e0153968.
3.	李克跃, 石承先, 汤可立, 等. 白细胞介素13对胆管成纤维细胞TGF-β1/Smads通路表达的影响及地塞米松的干预作用. 中国普通外科杂志, 2017, 26(8): 987-992.
4.	Du XH, Liu JQ, Xin K, et al. Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats. Braz J Med Biol Res, 2015, 48(4): 344-348.
5.	Li K, Shi C, Huang J, et al. Dexamethasone effect on the expression of transforming growth factor-β1/Smads signaling pathway in benign biliary stricture fibroblasts in rodent. J Coll Physicians Surg Pak, 2017, 27(3): 131-134.
6.	熊丽霞, 李文林, 蔡震宇, 等. 干扰素γ抑制IL-13对成纤维细胞的纤维化作用. 中国病理生理杂志, 2013, 29(3): 504-508.
7.	Lalountas M, Ballas KD, Michalakis A, et al. Postoperative adhesion prevention using a statin-containing cellulose film in an experimental model. Br J Surg, 2012, 99(3): 423-429.
8.	Morello S, Southwood LL, Engiles J, et al. Effect of intraperitoneal PERIDAN™ concentrate adhesion reduction device on clinical findings, infection, and tissue healing in an adult horse jejunojejunostomy model. Vet Surg, 2012, 41(5): 568-581.
9.	Yu L, Hu H, Chen L, et al. Comparative studies of thermogels in preventing postoperative adhesions and corresponding mechanisms. Biomater Sci, 2014, 2(8): 1100-1109.
10.	Nair SK, Bhat IK, Aurora AL. Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg, 1974, 108(6): 849-853.
11.	刘勇, 夏军强, 张琴. 腹腔镜直肠癌经腹会阴联合切除术中盆底腹膜重建对术后并发症的影响. 中国普外基础与临床杂志, 2016, 23(11): 1375-1378.
12.	马丽桃, 张二帅, 车轩, 等. 改性木葡聚糖温敏水凝胶预防大鼠腹腔粘连的实验研究. 广东医学, 2016, 37(21): 3184-3188.
13.	Lin LX, Yuan F, Zhang HH, et al. Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS One, 2017, 12(2): e0172088.
14.	Firszt R, Francisco D, Church TD, et al. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur Respir J, 2014, 43(2): 464-473.
15.	毛春芹, 曾莉, 陆兔林, 等. 川芎嗪纳米喷雾剂对大鼠腹腔粘连相关因子和纤溶系统影响的实验研究. 中国药理学通报, 2012, 28(1): 118-123.
16.	Saleiro D, Blyth GT, Kosciuczuk EM, et al. IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Sci Signal, 2018, 11(557): pii: eaap9921.
17.	高晓方, 崔社怀. 干扰素γ对实验大鼠肺纤维化的治疗作用及机制的初步研究. 第三军医大学学报, 2005, 27(2): 143-145.
18.	李璐, 王继华, 赵亚南, 等. IFN-γ对大鼠创面愈合中Smad7表达的影响. 中国美容医学, 2009, 18(2): 201-204.
19.	朱松涛. 干扰素γ联合坎地沙坦治疗肝纤维化的近期疗效观察. 中华全科医学, 2010, 8(10): 1268-1269.
20.	熊丽霞, 石小玉. IL-13对成纤维细胞胶原蛋白合成的影响及其分子调控机制. 南昌大学, 2007.
21.	Ramalingam TR, Gieseck RL, Acciani TH, et al. Enhanced protection from fibrosis and inflammation in the combined absence of IL-13 and IFN-γ. J Pathol, 2016, 239(3): 344-354.
22.	Lu J, Zhu Y, Feng W, et al. Platelet-derived growth factor mediates interleukin-13-induced collagen Ⅰ production in mouse airway fibroblasts. J Biosci, 2014, 39(4): 693-700.
23.	李雪梅, 翟丽东. 干扰素γ与甲强龙联合应用对人胚肺成纤维细胞增殖的影响. 中国组织工程研究与临床康复, 2008, 12(15): 2829-2833.
24.	王敏, 梁航, 王丽娜, 等. 干扰素γ治疗毛细支气管炎的疗效观察. 中国生物制品学杂志, 2012, 25(2): 228-229, 236.
25.	崔娟娟, 冯占芹, 张守强, 等. 羧甲基壳聚糖冲洗液预防大鼠术后腹膜粘连. 中国组织工程研究, 2014, 18(8): 1250-1256.

1. 刘国涛, 陈巧, 金丽明, 等. 丹参多酚酸盐联合聚维酮碘预防大鼠术后肠粘连. 浙江中西医结合杂志, 2015, 25(6): 538-541.
2. Bianchi E, Boekelheide K, Sigman M, et al. Ghrelin inhibits post-operative adhesions via blockage of the TGF-β signaling pathway. PLoS One, 2016, 11(4): e0153968.
3. 李克跃, 石承先, 汤可立, 等. 白细胞介素13对胆管成纤维细胞TGF-β1/Smads通路表达的影响及地塞米松的干预作用. 中国普通外科杂志, 2017, 26(8): 987-992.
4. Du XH, Liu JQ, Xin K, et al. Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats. Braz J Med Biol Res, 2015, 48(4): 344-348.
5. Li K, Shi C, Huang J, et al. Dexamethasone effect on the expression of transforming growth factor-β1/Smads signaling pathway in benign biliary stricture fibroblasts in rodent. J Coll Physicians Surg Pak, 2017, 27(3): 131-134.
6. 熊丽霞, 李文林, 蔡震宇, 等. 干扰素γ抑制IL-13对成纤维细胞的纤维化作用. 中国病理生理杂志, 2013, 29(3): 504-508.
7. Lalountas M, Ballas KD, Michalakis A, et al. Postoperative adhesion prevention using a statin-containing cellulose film in an experimental model. Br J Surg, 2012, 99(3): 423-429.
8. Morello S, Southwood LL, Engiles J, et al. Effect of intraperitoneal PERIDAN™ concentrate adhesion reduction device on clinical findings, infection, and tissue healing in an adult horse jejunojejunostomy model. Vet Surg, 2012, 41(5): 568-581.
9. Yu L, Hu H, Chen L, et al. Comparative studies of thermogels in preventing postoperative adhesions and corresponding mechanisms. Biomater Sci, 2014, 2(8): 1100-1109.
10. Nair SK, Bhat IK, Aurora AL. Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg, 1974, 108(6): 849-853.
11. 刘勇, 夏军强, 张琴. 腹腔镜直肠癌经腹会阴联合切除术中盆底腹膜重建对术后并发症的影响. 中国普外基础与临床杂志, 2016, 23(11): 1375-1378.
12. 马丽桃, 张二帅, 车轩, 等. 改性木葡聚糖温敏水凝胶预防大鼠腹腔粘连的实验研究. 广东医学, 2016, 37(21): 3184-3188.
13. Lin LX, Yuan F, Zhang HH, et al. Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS One, 2017, 12(2): e0172088.
14. Firszt R, Francisco D, Church TD, et al. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur Respir J, 2014, 43(2): 464-473.
15. 毛春芹, 曾莉, 陆兔林, 等. 川芎嗪纳米喷雾剂对大鼠腹腔粘连相关因子和纤溶系统影响的实验研究. 中国药理学通报, 2012, 28(1): 118-123.
16. Saleiro D, Blyth GT, Kosciuczuk EM, et al. IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Sci Signal, 2018, 11(557): pii: eaap9921.
17. 高晓方, 崔社怀. 干扰素γ对实验大鼠肺纤维化的治疗作用及机制的初步研究. 第三军医大学学报, 2005, 27(2): 143-145.
18. 李璐, 王继华, 赵亚南, 等. IFN-γ对大鼠创面愈合中Smad7表达的影响. 中国美容医学, 2009, 18(2): 201-204.
19. 朱松涛. 干扰素γ联合坎地沙坦治疗肝纤维化的近期疗效观察. 中华全科医学, 2010, 8(10): 1268-1269.
20. 熊丽霞, 石小玉. IL-13对成纤维细胞胶原蛋白合成的影响及其分子调控机制. 南昌大学, 2007.
21. Ramalingam TR, Gieseck RL, Acciani TH, et al. Enhanced protection from fibrosis and inflammation in the combined absence of IL-13 and IFN-γ. J Pathol, 2016, 239(3): 344-354.
22. Lu J, Zhu Y, Feng W, et al. Platelet-derived growth factor mediates interleukin-13-induced collagen Ⅰ production in mouse airway fibroblasts. J Biosci, 2014, 39(4): 693-700.
23. 李雪梅, 翟丽东. 干扰素γ与甲强龙联合应用对人胚肺成纤维细胞增殖的影响. 中国组织工程研究与临床康复, 2008, 12(15): 2829-2833.
24. 王敏, 梁航, 王丽娜, 等. 干扰素γ治疗毛细支气管炎的疗效观察. 中国生物制品学杂志, 2012, 25(2): 228-229, 236.
25. 崔娟娟, 冯占芹, 张守强, 等. 羧甲基壳聚糖冲洗液预防大鼠术后腹膜粘连. 中国组织工程研究, 2014, 18(8): 1250-1256.

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Experimental study of interferon-γ in preventing intestinal adhesion following abdominal surgery in rats

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