Sacral nerve stimulating on intestinal mucosal immune barrier function of rats with acute complete spinal cord injury

doi:10.12047/j.cjap.6023.2020.114

Abstract

Abstract: Objective: To study the effects of sacral nerve root stimulation on intestinal mucosal immune barrier function in rat with acute complete spinal cord injury(SCI). Methods: Fifty-six Wistar rats were divided into Sham group(SG n=8), control group(CG 24 、 48、 72 h,n=8), and experimental group(EG 24、 48、 72 h,n=8). In CG and EG, according to Fehlings'method,we transected the spinal cord by the aneurysm clip and implanted electrodes into the third sacral foramina on the right side.We stimulated in intensity 4 V,the frequency of 15 Hz,and the pulse of 210 μs.The stimulation period was 2 hours,with 10 minutes stimulation and 10 minutes rest intermittently,twice a day at 8:00-10:00 am and 6:00-8:00 pm. The intestinal morphology was observed under light microscope and electron microscope. The protein expression levels of A20,NOD2,and CD68 by Western blot . Results: ① SCI caused impaired intestinal epithelial barrier function. The intestinal mucosa appeared different degree of damage in CG group; cell-cell connections between intestinal epithelial cells were destroyed; The escherichia coli and other antigen translocated through the injured epithelial cell , M cells, and the leakage to the lamina propria of intestinal villi, which were improved in EG after stimulation.② The expression of A20 in EG was increased ,which had statistical differences between CG or SG(P＜0.01); the expression ofA20 in CG was decreased, which had statistical differences between SG(P＜0.01).The expression of NOD2 in CG was increased, which had statistical differences between SG(24 h,72 h P＜0.05; 48 h P＜0.01);The expression of NOD2 in EG (48 h ,72 h)was decreased, which had statistical differences between CG(48 h P＜0.01,72 h P＜0.05). The expression of NOD2 in EG had no statistical differences between SG. The expression of CD68 in CG was increased,which had statistical differences between SG or EG(P＜0.01).The expression of CD68 in EG was increased in 24 h and 48 h groups ,which had statistical differences between SG(P＜0.01),but had no statistical differences in 72 h group. Conclusion: Sacral nerve root 3 electrostimulation can rehabilitate the peristalsis of intestine,decrease bacterial amount,reduce inflammatory response, enhance endogenous protection, protect the intestinal mucosal immune barrier function.

Key words: spinal cord injury, sacral nerve stimulation, intestinal mucosal immune barrier function

CLC Number:

R454.1

BAI Chun-hong, ZHANG Wen-li, HU Shi-zhong. Sacral nerve stimulating on intestinal mucosal immune barrier function of rats with acute complete spinal cord injury[J]. CJAP, 2020, 36(6): 539-543.

References

[1] Bai C, An H, Wang S, et al. Treatment and prevention of bacterial translocation and endotoxemia with stimulation of the sacral nerve root in a rabbit model of spinal cord injury [J]. Spine, 2011, 36(5): 363-371.
[2] Liu C, Li A, Weng YB, et al. Changes in intestinal mucosal immune barrier in rats with endotoxemia[J]. World J Gastroenterol, 2009, 15(46): 5843-5850.
[3] Kayama H, Takeda K. Functions of innate immune cells and commensal bacteria in gut homeostasis [J]. J Biochem, 2016, 159(2): 141-149.
[4] Dillon A, Lo DD. M cells: Intelligent engineering of mucosal immune surveillance[J]. Front Immunol, 2019, 10: 1499.
[5] Albert-Bayo M, Paracuellos I, González-Castro AM, et al. Intestinal mucosal mast cells: Key modulators of barrier function and homeostasis[J]. Cells, 2019, 8(2): 135.
[6] Rodriguez-Lagunas MJ, Ferrer R, Moreno JJ. Effect of eicosapentaenoic acid-derived prostaglandin E3 on intestinal epithelial barrier function [J]. Prostaglandins Leukot Essent Fatty Acids, 2013, 88(5): 339-345.
[7] Zhang CX, Wang HY, Chen TX. Interactions between intestinal microflora/probiotics and the immune system[J]. Biomed Res Int, 2019: 6764919.
[8] Ganal-Vonarburg SC, Duerr CU.The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life[J]. Immunology, 2019, 159(1): 39-51.
[9] Haq S, Grondin J, Banskota S, et al. Autophagy: roles in intestinal mucosal homeostasis and inflammation[J]. J Biomed Sci, 2019, 26(1): 19.
[10] Yang J, Liu KX, Qu JM, et al. The changes induced by cyclophosphamide in intestinal barrier and microflora in mice [J]. Eur J Pharmacol, 2013, 714(1-3): 120-124.
[11] Soderholm AT, Pedicord VA. Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity[J]. Immunology, 2019, 158: 267-280.
[12] Bai CH, Ma XL.Ultrastructural study on route of gut bacterial translocation in a rat after spinal cord injury[J]. Chin J Appl Physiol, 2015, 31(6): 561-566.
[13] Bain CC, Origin AS. Differentiation, and function of intestinal macrophages[J]. Front Immunol, 2018, 9: 2733.
[14] Sousa JR De, Vasconcelos PF DC, Quaresma JAS. Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases[J]. Infect Drug Resist, 2019, 12: 2589-2611.
[15] Flannigan KL, Geem D, Harusato A, et al. Intestinal antigen-presenting cells key regulators of immune homeostasis and inflammation[J]. Am J Pathol, 2015, 185(7): 1809-1819.
[16] López-Santiago R, Sánchez-Argáez AB, Alba-Núnez LGD, et al. Immune response to mucosal brucella infection[J]. Front. Immunol, 2019, 10: 1759.
[17] Lee SH, Lee HR, Kwon JY, et al. A20 ameliorates inflammatory bowel disease in mice via inhibiting NF-κB and STAT3 activation[J]. Immunol Lett, 2018, 198: 44-51.
[18] Prasad AS, Bao B. Molecular mechanisms of zinc as a pro-antioxidant mediator: Clinical therapeutic implications[J]. Antioxidants, 2019, 8, 164: 1-22.
[19] Jarosz M, Olbert M, Wyszogrodzka G, et al. Antioxidant and anti-inflammatory effects of zinc-dependent NF-κB signaling[J]. Inflammopharmacology, 2017, 25: 11-24.
[20] Al Nabhani Z, Dietrich G, Hugot JP. Nod2: The intestinal gate keeper[J]. PLoS Pathog, 2017, 13(3): e1006177.
[21] Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract[J]. Science, 2005, 307(5710): 731-734.
[22] Normand S, Waldschmitt N, Neerincx A, et al. Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens[J]. Nat Commun, 2018, 9(1): 5338.