Effects of ulinastatin on intestinal mucosal barrier function in sepsis rats and its effect on wnt signal transduction pathway

WANG Yu-hui YE Ba-ning WU Jing LONG Da-li LI Kun SHI Xian-qing

Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (2) : 295-299.

PDF(2326 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(2326 KB)
Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (2) : 295-299. DOI: 10.16098/j.issn.0529-1356.2021.02.021
Histology,Embryology and Developmental Biology

Effects of ulinastatin on intestinal mucosal barrier function in sepsis rats and its effect on wnt signal transduction pathway

  • WANG Yu-hui*  YE Ba-ning  WU Jing  LONG Da-li  LI Kun  SHI Xian-qing
Author information +
History +

Abstract

Objective  To investigate the intestinal mucosal barrier function protective effect of ulinastatin in sepsis rats and its effect on Wnt/β-catenin signaling pathway.    Methods  One hundred  SD rats were randomly divided into control group, sepsis group, ulinastatin group, XAV939+ulinastatin group and  lithium chloride(LiCl)+ulinastatin group. The classical cecal ligation was used to duplicate sepsis model, and the jejunal mucosal injury was evaluated. The levels of inflammatory factors interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by ELISA, and the expressions of β-catenin and cyclin D1 were detected by Real-time PCR and Western blotting. We also observed the effect of the Wnt signal pathway blockage by XAV939 or Wnt signal pathway activator by LiCl on ulinastatin protection of intestinal mucosa and proteins related to the Wnt signal pathway.    Results  The levels of IL-6, TNF-α and intestinal mucosal injury in the sepsis group were significantly higher than those in the ulinastatin group. The mRNA and protein expression levels of β-catenin and cyclin D1 in the sepsis group were significantly higher than those in the control group (P<0.05), After ulinastatin treatment, the expression levels of β-catenin and cyclin D1 mRNA and protein were significantly decreased, and the difference was significant (P<0.05). Compared with the ulinastatin group, combined treatment with XAV939 promoted the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was reduced (P<0.05). Combined treatment with LiCl weakened the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was increased (P<0.05).    Conclusion  Ulinastatin may inhibit the Wnt signaling pathway by down-regulating the expression of β-catenin, reduce the expression of inflammatory factors IL-6 and TNF-α, thereby promote repairing the intestinal mucosal barrier function damage.

Key words

Ulinastatin / Sepsis / Intestinal mucosa / Wnt signal pathway / Western blotting / Rat

Cite this article

Download Citations
WANG Yu-hui YE Ba-ning WU Jing LONG Da-li LI Kun SHI Xian-qing. Effects of ulinastatin on intestinal mucosal barrier function in sepsis rats and its effect on wnt signal transduction pathway[J]. Acta Anatomica Sinica. 2021, 52(2): 295-299 https://doi.org/10.16098/j.issn.0529-1356.2021.02.021

References

[1] Jin PF, Chen L, Hu YR, et al. Progress of study on intestinal pathogenesis of sepsis[J]. Chinese Journal of Nosocomiology,2018,28(10):1441-1445. (in Chinese)
金鹏锋,陈琳,胡耀仁,等.脓毒症的肠道发病机制研究进展[J].中华医院感染学杂志,2018,28(10):1441-1445. 
[2] Khosravi A, Mazmanian SK. Disruption of the gut microbiome as a risk factor for microbial infections[J]. Curr Opin Microbiol,2013,16(2):221-227.
[3] Shi LL, Han YQ, Ren HJ, et al. Research advance of pathology and physiology of sepsis[J].Chinese Journal of Nosocomiology,2016,26(8):1914-1916. (in Chinese)

师灵灵,韩艳秋,任慧娟,等.脓毒症的病理生理机制研究进展[J].中华医院感染学杂志,2016,26(8):1914-1916.

[4] Yang J, Radulescu A, Chen CL, et al. Heparin-binding epidermal growth factor-like growth factor improves intestinal barrier function and reduces mortality in a murine model of peritonitis[J]. Surgery,2013,153(1):52-62.

[5] Linder A, Russell JA. Russell an exciting candidate therapy for sepsis: ulinastatin, a urinary protease inhibitor[J]. Intensive Care Med, 2014,40(8):1164-1167.
[6] Han D, Shang W, Wang G, et al. Ulinastatin- and thymosin α1-based immunomodulatory strategy for sepsis: a meta-analysis[J]. Int Immunopharmacol,2015, 29(2):377-382.
[7] Rodríguez-González R, Martín-Barrasa JL, Ramos-Nuez á, et al. Multiple system organ response induced by hyperoxia in a clinically relevant animal model of sepsis[J]. Shock, 2014, 42(2):148-153.
[8] Pugia MJ, Lott JA. Pathophysiology and diagonostic value of urinary trypsin inhibitors[J]. Clin Chem Lab Med, 2005,43(1):1-16.
[9] Chen ZhP. Effect of wnt/β-catenin signaling pathway on acute lung injury in sepsis[D]. Wuhan: Huazhong University of Science and Technology,2016.  (in Chinese)
陈正平. Wnt/β-catenin信号通路对脓毒症急性肺损伤的影响[D].武汉:华中科技大学,2016. 
[10] Cai,YY, Zhou JP, Hu Q, et al. Effect of Wnt/β-catenin signaling pathway on the repair of orthodontic root, resorption[J]. Journal of Chongqing Medical University,2018,43(8):1109-1115. (in Chinese)
蔡洋伊,周建萍,胡琴,等.Wnt/β-catenin信号通路对正畸牙根吸收后修复作用的研究[J].重庆医科大学学报,2018,43(8):1109-1115. 
[11] Wang H, Mao JL, Wu YM, et al. Protective effect of Zhenrenyangzang decoction on intestinal mucosal bar-rier function in ulcerative colitis rats[J]. Chinese Journal of Pathophysiology,2017,33(11):2053-2059. (in Chinese)
王慧,毛晶磊,吴艳敏,等.真人养脏汤对溃疡性结肠炎大鼠肠道黏膜屏障功能的保护作用[J].中国病理生理杂志,2017,33(11):2053-2059. 
[12] Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method[J]. Nat Protoc, 2008, 3(6): 1101-1108.
[13] Xie F, Min S, Chen J, et al. Ulinastatin inhibited sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction in an experimental rat model of neuromyopathy[J]. J Neurochem, 2017,143(2): 225-235.
[14] Liang Q, Diao BB, Wang C. Effect of Yiqi Yangyin Huoxue recipe on serum TNF-α, IL-6 and IL-10 in septic model rats[J]. Chinese Journal of Immunology, 2014,11(12):1705-1707. (in Chinese)
梁群, 刁冰冰, 王丛. 益气养阴活血法对脓毒症模型大鼠血清TNF-α、IL-6与IL-10的影响[J].中国免疫学杂志, 2014,11(12):1705-1707. 
[15] Tian A, Benchabane H, Wang Z, et al. Regulation of stem cell proliferation and cell fate specification by Wingless/Wnt signaling gradients enriched at adult intestinal compartment boundaries[J]. PLoS Genetics, 2016, 12(2):e1005822.
[16] Yao LH. Advanced glycation end product receptors participate in the regulation of TDI asthma airway inflammation by stabilizing β-catenin signaling[D]. Guangzhou: Southern Medical University,2017.  (in Chinese)
姚利红. 晚期糖基化终末产物受体通过稳定β-catenin信号参与调控TDI哮喘气道炎症[D].广州:南方医科大学,2017. 
[17] Zhu YT, Guo Y, Qiao YY, et al. Verbenalin inhibits airway inflammation and remodeling by modulating Wnt/β-catenin signal pathway in asthma rats[J]. The Journal of Practical Medicine,2018,34(17):2880-2883. (in Chinese)
朱颖涛,郭燕,乔岩岩,等.马鞭草苷通过Wnt/β-catenin信号通路干预哮喘大鼠气道炎症及气道重塑的研究[J].实用医学杂志,2018,34(17):2880-2883.
PDF(2326 KB)

Accesses

Citation

Detail

Sections
Recommended

/