溃疡性结肠炎患者肠黏膜P糖蛋白的表达及其临床意义

doi:10.6040/j.issn.1671-7554.0.2020.0753

摘要/Abstract

摘要： 目的研究溃疡性结肠炎(UC)患者激素治疗前后肠黏膜上皮细胞P糖蛋白(P-GP)的表达水平以及P-GP与外周血内毒素和D-乳酸含量的相关性,探讨其与UC发病的关系。方法初治UC患者102例,健康对照者31例。采用免疫组织化学法(SP法)检测UC患者治疗前后以及健康对照者肠黏膜上皮细胞P-GP的表达水平;分别采用ELISA法和紫外分光光度计法检测UC患者治疗前后以及健康对照者外周血内毒素和D-乳酸水平。结果与健康对照组比较,治疗前UC患者外周血内毒素［(0.67±0.58)vs(18.15±0.73), P<0.01］和D-乳酸［(1.75±1.25)vs(10.85±1.94),P<0.05］水平升高,而肠黏膜上皮P-GP表达水平降低,差异均有统计学意义;接受激素治疗2个月后, UC患者肠黏膜上皮P-GP表达总阳性率和强阳性率显著高于激素治疗前水平,差异有统计学意义(P<0.05)。UC患者治疗前后外周血内毒素和D-乳酸浓度与肠黏膜P-GP表达水平呈负相关。结论 UC患者肠黏膜屏障受损、通透性增加可能与肠黏膜P-GP表达水平低下有关,肠黏膜P-GP表达水平与UC发病可能具有相关性。

关键词: 溃疡性结肠炎, P糖蛋白, 多药耐药基因, 肠黏膜屏障

Abstract: Objective To detect the expression of P-glycoprotein(P-GP)in the colonic mucosa of patients with ulcerative colitis(UC)before and after hormonotherapy, explore its correlation with the peripheral endotoxin and D-lactic acid levels, and investigate its association with UC. Methods Previously untreated UC patients(n=102)and healthy controls(n=31)were selected. The expression of P-GP in the colonic mucosa of UC patients before and after treatment, and that of healthy controls were detected with immunohistochemistry. The peripheral endotoxin and D-lactic acid levels were detected with ELISA and ultraviolet spectrophotometry respectively. Results Before hormonotherapy, the peripheral endotoxin ［(0.67±0.58)vs(18.15±0.73), P<0.01］ and D-lactic acid level ［(1.75±1.25)vs(10.85±1.94), P<0.05］ of UC patients were higher than those of healthy controls, while the expression of P-GP was lower(P<0.05). Two months after hormonotherapy, the total positive rate and strong positive rate of UC patients were significantly higher than the rates before therapy(P<0.05). The peripheral endotoxin and D-lactic acid levels before and after hormonotherapy were negatively correlated with P-GP expression. Conclusion The impaired intestinal barrier and increased intestinal permeability in UC patients may be related to the low expression of P-GP in intestinal mucosa. The P-GP expression may be correlated with the pathogenesis of ulcerative colitis.

Key words: Ulcerative colitis, P-glycoprotein, Multidrug resistance gene, Intestinal mucosa barrier

中图分类号:

R574

付振美,马铭泽. 溃疡性结肠炎患者肠黏膜P糖蛋白的表达及其临床意义[J]. 山东大学学报 (医学版), 2020, 58(12): 54-59.

FU Zhenmei, MA Mingze. Expression of P-glycoprotein in the colonic mucosa of ulcerative colitis patients and its clinical significance[J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 54-59.

参考文献

[1] 中华医学会消化病学分会炎症性肠病协作组.对我国炎症性肠病诊断治疗规范的共识意见[J]. 中华消化杂志, 2007, 27(8): 545-550.
[2] 许冬梅, 张源潮, 杨清锐. 多药耐药基因敲除小鼠结肠炎的免疫病理改变[J]. 中华消化杂志, 2005, 25(2): 71-74. XU Dongmei, ZHANG Yuanchao, YANG Qingrui. Pathological manifestion of MDR1 gene knockout mice related mice colitis[J]. Chinese Journal of Digestion, 2005, 25(2): 71-74.
[3] Burman S, Hoedt EC, Pottenger S, et al. An(Anti)-inflammatory microbiota: defining the role in inflammatory bowel disease? [J]. Dig Dis, 2016, 34(1-2): 64-71.
[4] Chu H, Khosravi A, Kusumawardhani IP, et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease [J]. Science, 2016, 352(6289): 1116-1120.
[5] Chung CS, Chang PF, Liao CH, et al. Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects [J]. Scand J Gastroenterol, 2016, 51(4):410-419.
[6] Collins SM. The intestinal microbiota in the irritable bowel syndrome [J]. Int Rev Neurobiol, 2016, 131: 247-261. doi:org/1016/bs.im.2016.08.003.
[7] Dior M, Delagreverie H, Duboc H, et al. Interplay between bile acid metabolism and microbiota in irritable bowel syndrome [J]. Neurogastroenterol Motil, 2016, 28(9): 1330-1340.
[8] Farnood A, Naderi N, Moghaddam SJ, et al. The frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis [J]. Int J Colorectal Dis, 2007, 22(9): 999-1003.
[9] Yacyshyn B, Maksymowych W, Bowen-Yacyshyn MB, et al. Differences in P-glycoprotein-170 expression and activity between Crohns disease and ulcerative colitis [J]. Hum Immunol, 1999, 60(8): 677-687
[10] Fiedler T, Büning C, Reuter W, et al. Possible role of MDR1 two-locus genotypes for young-age onset?ulcerative colitis but not Crohns disease [J]. Eur J Clin Pharmacol, 2007, 63(10): 917-925.
[11] Filip AT, Balacescu O, Marian C, et al. Microbiota small RNAs in inflammatory bowel disease [J]. Gastrointestin Liver Dis, 2016, 25(4): 509-516.
[12] Wang XH, Li D, Zhang Y, et al. Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway [J]. Exp Ther Med, 2018, 15(5): 4477-4484.
[13] Xue Bing, Liang Linlang, Chen Keyan. Decreased Breg/Th17 ratio improved the prognosis of patients with ulcerative colitis [J]. Can J Gastroenterol Hepatol, 2018, 2018: 5760849. doi: 10.1155/2018/5760849.
[14] Dominika Gbska, Dominika Guzek, Gustaw lech. Nutritional status of men with ulcerative colitis in remission in a pair-matched case-control study [J]. J Clin Med, 2018, 7(11): 438.
[15] Lauren E. Hudson, Sarah E, et al. Gleaning insights from fecal microbiota transplantation and probiotic studies for the rational design of combination microbial therapies [J]. Clin Microbiol Rev, 2017, 30(1): 191-231.
[16] P. Kump, P. Wurm, H. P. Gröchenig, et al. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis [J]. Aliment Pharmacol Ther, 2018, 47(1): 67-77.
[17] Bui K, She F, Zhou D et al. The effect of quinidine, a strong P-glycoprotein inhibitor, on the pharmacokinetics and central nervous system distribution of naloxegol [J]. J Clin Pharmacol, 2016, 56(4): 497-505.
[18] Choi JY, Song JS, Lee M et al. P-Glycoprotein, not BCRP, limits the brain uptake of [18F] mefway in rodent brain [J]. Mol Imaging Biol, 2016, 18(2): 267-273.
[19] Han L, Ma YM, An L et al. Non-alkaloids extract from Stemona sessilifolia enhances the activity of chemotherapeutic agents through P-glycoprotein-mediated multidrug-resistant cancer cells [J]. Natural Product Research, 2016, 30(10): 1186-1189.
[20] Hofman J, Kucera R, Neumanova Z, et al. Placental passage of olomoucine II, but not purvalanol A, is affected by p-glycoprotein(ABCB1), breast cancer resistance protein(ABCG2)and multidrug resistance-associated proteins(ABCCs)[J]. Xenobiotica, 2016, 46(5): 416-423.
[21] Kansal A, Tripathi D, Rai MK, et al. Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus [J]. Clin Rheumatol, 2016, 35(2): 341-349.
[22] Kumar A, Mishra J, Chopra K, et al. Possible role of P-glycoprotein in the neuroprotective mechanism of berberine in intracerebroventricular streptozotocin-induced cognitive dysfunction [J]. Psychopharmacology, 2016, 233(1): 137-152.
[23] Liu JS, He YJ, Zhang J, et al. Functionalized nanocarrier combined seizure-specific vector with P-glycoprotein modulation property for antiepileptic drug delivery [J]. Biomaterials, 2016, 74: 64-76. doi: 10.1016/j.biomaterials.2015.09.041.
[24] Liu J, Wang M, Zhang XL, et al. CIP2A is associated with multidrug resistance in cervical adenocarcinoma by a P-glycoprotein pathway [J]. Tumour Biol, 2016, 37(2): 2673-2682.
[25] Marcos Prieto HM, Perez Corte D, Pinero Perez MC, et al. Acute pancreatitis secondary to partial multidrug resistance 3 p-glycoprotein deficit [J]. Gastroenterol Hepatol, 2016, 39(7): 465.

相关文章 15

[1]	葛丽娟金瑞峰王纪文许新升李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 99-102.
[2]	李霞,李理想,李铭,陈飞雪,左秀丽,李延青. 促肾上腺皮质激素释放因子对肠道杯状细胞分泌产物的影响[J]. 山东大学学报（医学版）, 2017, 55(4): 44-49.
[3]	陈涛英. 临床护理路径在溃疡性结肠炎患者中的应用[J]. 山东大学学报（医学版）, 2014, 52(S2): 136-136.
[4]	张庆伟1，王春亭2，王启志2，张琳2，王鹏2，孟玫2. 丙酮酸乙酯对脓毒症大鼠小肠黏膜屏障的保护作用及其机制[J]. 山东大学学报（医学版）, 2014, 52(5): 30-34.
[5]	车千红,郭佳琦. 免疫肠内营养联合药物治疗溃疡性结肠炎的疗效[J]. 山东大学学报(医学版), 2013, 51(7): 75-78.
[6]	李霄，郝洪升. Baron分级对溃疡性结肠炎黏膜愈合的预测作用[J]. 山东大学学报(医学版), 2013, 51(12): 67-69.
[7]	李海素，杨崇美. DPP-4抑制剂治疗小鼠溃疡性结肠炎的疗效[J]. 山东大学学报(医学版), 2013, 51(12): 29-33.
[8]	李玲，陈勇，杨崇美. 溃疡性结肠炎激素敏感性与多药耐药基因多态性的相关性研究[J]. 山东大学学报(医学版), 2012, 50(5): 99-102.
[9]	刘胜楠，卢雪峰，孙娜，郑雪婷，李倩倩. Toll样受体2、4及核因子-κB在溃疡性结肠炎黏膜组织中的表达及临床意义[J]. 山东大学学报(医学版), 2012, 50(2): 60-.
[10]	李梅1,2,高艳景1,崔祥华1，徐咏梅3. 前列腺素受体EP2在溃疡性结肠炎黏膜中的表达及临床意义[J]. 山东大学学报(医学版), 2012, 50(11): 79-83.
[11]	孟宪邑，张芸，吴震州. 娃儿藤碱类化合物DCB-3503对TNBS诱导溃疡性结肠炎的治疗作用[J]. 山东大学学报(医学版), 2012, 50(10): 81-.
[12]	江娜. 奥沙拉嗪联合甘草酸二铵对溃疡性结肠炎患者脂质过氧化损伤和IL-1β水平的影响[J]. 山东大学学报(医学版), 2011, 49(9): 114-116.
[13]	王志强1,2，于振海2，袁方曙1. 双歧杆菌对溃疡性结肠炎大鼠肠黏膜上皮细胞Toll样受体2、4及NF-κB基因表达的影响[J]. 山东大学学报(医学版), 2011, 49(5): 10-14.
[14]	马铭泽,张安忠,蒯景华,杨崇美. 溃疡性结肠炎患者食物特异性抗体的检测和剔除过敏食物对临床疗效的影响[J]. 山东大学学报(医学版), 2011, 49(1): 86-89.
[15]	葛丽娟金瑞峰王纪文许新升李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2009, 47(6): 99-102.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed