余甘子提取物对非酒精性脂肪性肝病大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响*

doi:10.3969/j.issn.1672-5069.2020.04.009

摘要/Abstract

摘要： 目的探讨余甘子提取物对非酒精性脂肪性肝病(NAFLD)大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响。方法将48只SD大鼠随机分对照组、模型组、多烯磷脂酰胆碱及小剂量、中剂量和大剂量余甘子处理组,在造模成功后,给予对照组生理盐水灌胃,给予模型组多烯磷脂酰胆碱处理,另给予不同剂量的余甘子灌胃处理,连续给药6周。采用ELISA法检测血清TNF-α、IL-17和IL-10水平,使用流式细胞术检测血CD4⁺IL-17⁺和CD4⁺CD25⁺Treg细胞百分比,采用WB法检测肝组织LXRα和FAS蛋白表达。结果与模型组比,大剂量余甘子提取物处理组肝组织病理学损伤显著改善,血清ALT、AST、TC、TG水平显著降低(P<0.05);血清TNF-α和IL-17水平显著降低,分别为(34.7±0.9)pg/ml和(3.2±0.2)pg/mL,而IL-10水平显著升高,为(4.8±0.2)pg/mL(P<0.05);大剂量余甘子处理组CD4⁺IL-17⁺百分比为(1.1±0.6)%,显著低于模型组[(1.9±0.4)%,P<0.05],CD4⁺CD25⁺Treg百分比为(1.5±0.6)%,显著高于模型组[(0.9±0.2)%,P<0.05];小、中、大剂量余甘子提取物处理组肝组织LXRα和FAS蛋白表达显著减弱[分别为(1.8±0.1)和(2.0±0.2),P<0.05]。结论余甘子提取物可改善NAFLD大鼠肝组织病理学损伤,可能与其对炎性细胞因子、Th17/Treg细胞和LXRα/FAS通路因子的表达产生了某种影响有关。

关键词: 非酒精性脂肪性肝病, 余甘子提取物, 细胞因子, CD4⁺IL-17⁺细胞, CD4⁺CD25⁺Treg细胞, LXRα/FAS通路, 大鼠

Abstract: Objective To investigate the effects of Phyllanthus emblica extract on hepatic LXRα/FAS pathway protein expression in rats with non-alcoholic fatty liver disease (NAFLD). Methods A total of 48 SD rats were randomly divided into control group, model group, polyene phosphatidylcholine group, low-dose, moderate-dose and high-dose Phyllanthus emblica-intervened groups. After the successful establishment of the model, except for in the control group and in the model group, the rats were given intragastric administration of agents for 6 weeks. The histopathological changes of liver were examined, serum TNF-α, IL-17 and IL-10 levels were detected by ELISA, and the percentages of peripheral blood CD4⁺IL-17⁺and CD4⁺CD25⁺Treg cells were detected by flow cytometry, and the expression of LXRα and FAS in liver tissues were detected by WB. Results Compared with in the model group, the administration of high dose of Phyllanthus emblica extract could improve the pathological changes of liver tissues, serum ALT, AST, TC and TG levels were significantly decreased, serum TNF-α and IL-17 levels were (34.7±0.9) pg/ml and (3.2±0.2) pg/mL, significantly decreased, while serum IL-10 level was significantly increased, e.g. (4.8±0.2 pg/mL,P<0.05); the percentage of CD4⁺IL-17⁺ cells in the high-dose of Phyllanthus emblica intervention was (1.1±0.6)%, significantly lower than [(1.9±0.4)%, P<0.05]in the model group, the percentage of CD4⁺CD25⁺Treg was (1.5±0.6)%, significantly higher than in the model group [(0.9±0.2)%, P<0.05]; the hepatic expression of LXRα and FAS in the small, moderate and high dose ofPhyllanthus emblica extract-intervened groups were significantly decreased [(1.8±0.1) and (2.0±0.2),P<0.05]compared to those in the model. Conclusion The extract of Phyllanthus emblica could improve the histopathological changes of liver tissues of rats with NAFLD, which might be related to the inhibition of inflammatory cytokines and hepatic LXRα/ FAS expression as well as modulation of Th17/Treg cells.

Key words: Nonalcoholic fatty liver disease, Extractum Phyllanthus emblica, CD4⁺IL-17⁺ cells, CD4⁺CD25⁺Treg cells, LXRα/FAS, Rats

胡亦懿, 翟英姬, 梅迪华, 张志侨, 罗晓亮, 黄燕峰, 杜国平. 余甘子提取物对非酒精性脂肪性肝病大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响^*[J]. 实用肝脏病杂志, 2020, 23(4): 488-491.

Hu Yiyi, Zhai Yingji, Mei Dihua, et al. Effects of extractum Phyllanthus emblica on hepatic LXRα/ FAS pathway expression in rats with nonalcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2020, 23(4): 488-491.

参考文献

[1]王艳,苏峰,李园园,等.蜂毒溶血肽改善非酒精性脂肪肝大鼠肝组织脂肪沉积作用及其机制研究.实用肝脏病杂志,2019,22(4):474-477.
[2]张胥磊,杨庆余,韩秋玉,等.自拟中药治疗非酒精性脂肪性肝病患者血清炎症反应指标水平的变化.实用肝脏病杂志,2019,22(5):660-663.
[3]Cai J, Zhang XJ, Li H. Role of innate immune signaling in non-alcoholic fatty liver disease. Trends Endocrinol Metab, 2018, 29(10): 712-722.
[4]Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: a review. World J Gastroenterol, 2017, 23(36): 6549.
[5]Chaphalkar R, Apte KG, Talekar Y, et al. Antioxidants of Phyllanthus emblica L. bark extract provide hepatoprotection against ethanol-induced hepatic damage: a comparison with silymarin. Oxid Med Cell Longev, 2017, 2017: 3876040.
[6]Dinesh M, Roopan SM, Selvaraj CI, et al. Phyllanthus emblica seed extract mediated synthesis of PdNPs against antibacterial, heamolytic and cytotoxic studies. J Photochem Photobiol A Chem, 2017, 167: 64-71.
[7]Leoni S, Tovoli F, Napoli L, et al. Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol, 2018, 24(30): 3361.
[8]Cobbina E, Akhlaghi F. Non-alcoholic fatty liver disease (NAFLD)–pathogenesis, classification, and effect on drug metabolizing enzymes and transporters. Drug Metab Rev, 2017, 49(2): 197-211.
[9]Zhu JZ, Zhou QY, Wang YM, et al. Prevalence of fatty liver disease and the economy in China: a systematic review. World J Gastroenterol, 2015, 21(18): 5695.
[10]Zhang M, Yuan Y, Wang Q, et al. The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα. Biosci Rep, 2018, 38(6): BSR20180644.
[11]Liang Y, Zhang Y, Deng Y, et al. Chaihu-Shugan-San decoction modulates intestinal microbe dysbiosis and alleviates chronic metabolic inflammation in NAFLD rats via the NLRP3 inflammasome pathway. Evid Based Complement Alternat Med, 2018, 2018:9390786.
[12]He B, Wu L, Xie W, et al. The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice. BMC Immunol, 2017, 18(1): 33.
[13]程雪,单永业,罗亚文.Th17/调节性T淋巴细胞比率在急性乙型肝炎患者外周血的动态变化及其意义.中华肝脏病杂志,2016,24(8):565-568.
[14]Li Y, Jiang HT, Han LB, et al. MiR-195 regulates CD40 to maintain Th17/Treg balance in rats with non-alcoholic fatty liver disease. Biomed Pharmacother, 2020, 124: 109930.
[15]Rau M, Schilling AK, Meertens J, et al. Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis is marked by a higher frequency of Th17 cells in the liver and an increased Th17/resting regulatory T cell ratio in peripheral blood and in the liver. J Immunol, 2016, 196(1): 97-105.
[16]Gomes A L, Teijeiro A, Burén S, et al. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell, 2016, 30(1): 161-175.
[17]Su L, Wu Z, Chi Y, et al. Mesenteric lymph node CD4⁺ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease. Cell Immunol, 2019, 337: 33-41.
[18]Chackelevicius CM, Gambaro SE, Tiribelli C, et al. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis. World J Gastroenterol, 2016, 22(41): 9096.
[19]李红山,陈少东,应豪,等.红景天苷对高脂饮食诱导的大鼠非酒精性脂肪肝肝脏脂肪合成和氧化环节的干预作用.中华中医药杂志,2017,32(10):4625-4628.
[20]Wang D, Lao L, Pang X, et al. Asiatic acid from potentilla chinensis alleviates non-alcoholic fatty liver by regulating endoplasmic reticulum stress and lipid metabolism. Int Immunopharmacol, 2018, 65: 256-267.

余甘子提取物对非酒精性脂肪性肝病大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响^*

Effects of extractum Phyllanthus emblica on hepatic LXRα/ FAS pathway expression in rats with nonalcoholic fatty liver disease

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	杨涓. 茵陈四苓颗粒对胆汁淤积性肝炎大鼠肝功能损害的改善作用及其机制研究^*[J]. 实用肝脏病杂志, 2020, 23(4): 476-479.
[2]	汪可, 崔现平, 刘丽娟, 支庆江, 姜文营. 蓝莓花青素干预肝硬化大鼠肝组织凋亡蛋白表达的变化^*[J]. 实用肝脏病杂志, 2020, 23(4): 480-483.
[3]	李爽, 刘金玉, 武晓玉, 王宏雅, 刘慧萍, 赵欣, 蔡大勇. 氯膦酸二钠脂质体清除肝内巨噬细胞对CCl₄诱导的慢性肝损伤大鼠门脉高压的影响^*[J]. 实用肝脏病杂志, 2020, 23(4): 484-487.
[4]	侯光华, 胡启江, 徐美华, 朱绍咏, 黄波. 多烯磷脂酰胆碱联合二甲双胍和非诺贝特治疗NAFLD患者血清Pygo2和血脂水平变化^*[J]. 实用肝脏病杂志, 2020, 23(4): 528-531.
[5]	周娜, 蒋磊, 吴冰冰. 阿托伐他汀治疗NAFLD患者对肝脂肪变和外周血Treg/Th17细胞的影响^*[J]. 实用肝脏病杂志, 2020, 23(4): 532-535.
[6]	沈玉根, 徐东林. 双镜微创术联合术后吲哚美辛栓治疗胆囊结石合并胆总管结石患者效果研究^*[J]. 实用肝脏病杂志, 2020, 23(4): 605-608.
[7]	吴鹏波,宋琪,俞媛洁,郭一天,饶倩,柴红,谭诗云. 姜黄素对非酒精性脂肪肝细胞模型保护作用以及机制研究[J]. 实用肝脏病杂志, 2020, 23(3): 324-327.
[8]	唐晓飞,钟梦菊,沈海娟. 柚皮素脂质体对非酒精性脂肪性肝病大鼠脂质代谢的影响及机制研究[J]. 实用肝脏病杂志, 2020, 23(3): 328-331.
[9]	唐新亚,侯森,焦营营. 卡托普利对非酒精性脂肪性肝病大鼠肝细胞脂肪变性的影响[J]. 实用肝脏病杂志, 2020, 23(3): 332-335.
[10]	艾国,王鸣,朱纪玲,邢铭友. 应用N-乙酰半胱氨酸治疗慢性乙型肝炎重度患者临床疗效初步研究[J]. 实用肝脏病杂志, 2020, 23(3): 336-339.
[11]	张亚男,范竹萍. 运动处方应用于非酒精性脂肪性肝病患者治疗作用和安全性评价[J]. 实用肝脏病杂志, 2020, 23(3): 360-363.
[12]	沈金勇,郭翔云,周辉,罗乐. Hp根治治疗对非酒精性脂肪性肝病患者血清细胞因子和血脂水平的影响[J]. 实用肝脏病杂志, 2020, 23(3): 364-367.
[13]	钱锦,沈彤,汪泳. 腹腔镜下袖状胃切除术治疗非酒精性脂肪性肝病患者改善糖脂代谢紊乱[J]. 实用肝脏病杂志, 2020, 23(3): 372-375.
[14]	王丽君,靳广甫,王齐,吴丹,李素娟. 代谢综合征患儿肝前脂肪厚度和腰围变化[J]. 实用肝脏病杂志, 2020, 23(3): 376-379.
[15]	张猛, 陈晹, 刘娇, 李叶晟, 黄杨卿. 非酒精性脂肪性肝病小鼠肝组织与脂质代谢相关基因FAS、ACC和SREBP-1水平分析^*[J]. 实用肝脏病杂志, 2020, 23(2): 163-166.