切换至 "中华医学电子期刊资源库"
高级检索
中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2018, Vol. 13 ›› Issue (06) : 450 -454. doi: 10.3877/cma.j.issn.1673-9450.2018.06.010

所属专题： 文献；

论著

胆汁酸对肝硬化大鼠肝切除术后法尼酯X受体、白细胞介素－6的表达及肝功能恢复的影响
杜汉朋1,†(), 陈伟2, 孔凡东1, 吴铭1   
  1. 1. 511400　广州，南方医科大学附属何贤纪念医院普通外科
    2. 510080　广州，中山大学附属第一医院胆胰外科
  • 收稿日期:2018-10-12 出版日期:2018-12-01
  • 通信作者: 杜汉朋
  • 基金资助:
    广东省科技计划项目(2017ZC0432)

Effect of bile acid on expression of farnesoid X receptor, interleukin-6 and recovery of liver function after hepatectomy in rats with cirrhosis of liver

Hanpeng Du1,†(), Wei Chen2, Fandong Kong1, Ming Wu1   

  1. 1. Department of General Surgery, Hexian Memorial Hospital, Affiliated to Southern Medical University, Guangzhou 511400, China
    2. Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
  • Received:2018-10-12 Published:2018-12-01
  • Corresponding author: Hanpeng Du
  • About author:
    Corresponding author: Du hanpeng, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

杜汉朋, 陈伟, 孔凡东, 吴铭. 胆汁酸对肝硬化大鼠肝切除术后法尼酯X受体、白细胞介素－6的表达及肝功能恢复的影响[J]. 中华损伤与修复杂志(电子版), 2018, 13(06): 450-454.

Hanpeng Du, Wei Chen, Fandong Kong, Ming Wu. Effect of bile acid on expression of farnesoid X receptor, interleukin-6 and recovery of liver function after hepatectomy in rats with cirrhosis of liver[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2018, 13(06): 450-454.

目的

探讨胆汁酸对肝硬化大鼠肝切除术后法尼酯X受体(FXR)、白细胞介素-6(IL-6)的表达和肝功能恢复的影响作用。

方法

将24只SD大鼠采用0.03%硫代乙酰胺溶液喂养方法制备肝硬化模型，行肝切除术后采用简单随机法分为对照组和实验组，每组各12只。其中对照组用普通标准饲料喂养，而实验组用含0.2%胆汁酸的饲料喂养。1周后抽取下腔静脉血液行肝功能检查，随后处死实验动物，迅速切取残肝组织备用。分别采用蛋白质印迹法和全自动化学发光分析等方法检测FXR、IL-6的表达及肝功能恢复情况。数据比较采用t检验。

结果

实验组中天冬氨酸基转移酶(AST)、丙氨酸转氨酶(ALT)和体内胆汁酸水平分别为(156.4±32.5) U/L、(203.3±38.6) U/L、(6.68±3.90) μmol/L，均低于对照组(215.6±42.3) U/L、(273.8±42.1) U/L、(6.51±4.30) μmol/L，差异均有统计学意义(t＝4.432、2.566、2.114，P＝0.004、0.025、0.035)；实验组中FXR的表达量为0.45±0.16，而对照组的表达量为0.28±0.08，差异有统计学意义(t＝4.47，P＝0.003)；实验组中肝脏再生指标肝细胞有丝分裂指数(MI)、肝细胞增殖细胞核抗原(PCNA)标记指数和细胞核DNA含量分别为(2.89±0.67)%，(4.76±0.89)%和(8.82±2.12)%，均高于对照组(1.12±0.34)%，(2.46±0.68)%和(3.98±1.16)%，差异均有统计学意义(t＝4.688、5.069、6.858，P＝0.003、0.006、0.005)；而实验组中IL-6的水平为(1.34±0.56) ng/mL，对照组为(1.68±0.55) ng/mL，实验组明显低于对照组，差异有统计学意义(t＝2.29，P＝0.02)。

结论

胆汁酸可以通过启动FXR、减少IL-6炎性介质、促进大鼠肝功能恢复和肝脏再生。

关键词: 肝硬化, 肝切除术, 肝再生, 胆汁酸
Objective

To evaluate the effect of bile acid on the expression of farnesoid X receptor, interleukin-6 and recovery of liver function after hepatectomy in rats with cirrhosis of liver.

Methods

The liver cirrhosis model was prepared by feeding 24 SD rats with 0.03% thioacetamide solution. After the hepatectomy, the rats were divided into control group and experimental group by simple random method, 12 rats in each group. The control group was fed with normal standard feed, while the experimental group was fed with a diet containing 0.2% bile acid. One week later, the inferior vena cava blood was taken for liver function test, and then the experimental animals were sacrificed, and the residual liver tissue was quickly taken out for use. The expression of FXR and IL-6 and the recovery of liver function were detected by Western blotting and automatic chemiluminescence analysis. Data comparison was performed using the t test.

Results

Aspartate aminotransferase(AST), alanine transaminase(ALT) and in vivo bile acid levels in the experimental group were (156.4±32.5) U/L, (203.3±38.6) U/L, (6.68±3.90) μmol/L, which was lower than the control group (215.6±42.3) U/L, (273.8±42.1) U/L, (6.51±4.30) μmol/L, the difference was statistically significant (t=4.432, 2.566, 2.114, P=0.004, 0.025, 0.035); The hepatic mitotic index(MI), hepatocyte proliferating cell nuclear antigen(PCNA) labeling index and nuclear DNA content in the experimental group were (2.89±0.67)%, (4.76±0.89)% and (8.82±2.12)%, which were higher than the control group (1.12±0.34)%, (2.46±0.68)% and (3.98±1.16)%, the difference was statistically significant (t=4.688, 5.069, 6.858, P=0.003, 0.006, 0.005). The level of IL-6 in the experimental group was (1.34±0.56) ng/mL, and that in the control group was (1.68±0.55) ng/mL. The experimental group was significantly lower than the control group, and the difference was statistically significant (t=2.29, P=0.02).

Conclusion

Bile acid can promote FXR, reduce IL-6 inflammatory mediators, promote liver function recovery and liver regeneration in rats.

Key words: Liver cirrhosis, Hepatectomy, Liver regeneration, Bile acid
表1 探针和引物序列
扩增基因 序列
核受体X ?
? 探针 5′-Fam-TGGGAAATGTGCCTGAATGT-tamra-3′
? 上游引物 5′-TGCGGTTGAAGCTATGTTCCT-3′
? 下游引物 5′-TGAGTCATTTTCAGTTCCCCAAT-3′
GAPDH ?
? 探针 5′-Fam-TCCATCCTGGCCCCTCGCTGTGCA-tamra-3′
? 上游引物 5′-CGAATTTGCCTACAGCAACAG-3′
? 下游引物 5′-GACTGAGTGTGGCAGGGACTC-3′
表2 2组肝硬化大鼠肝切除术后肝功能水平比较(±s)
组别 鼠数(只) AST(U/L) ALT(U/L) 白蛋白(g/L) 体内胆汁酸(μmol/L)
实验组 12 156.4±32.5 203.3±38.6 22.5±3.9 6.68±3.90
对照组 12 215.6±42.3 273.8±42.1 30.6±5.6 6.51±4.30
t值 ? 4.432 2.566 3.449 2.114
P值 ? 0.004 0.025 0.008 0.035
图1 2组肝硬化大鼠肝切除术后FXR表达水平比较。FXR为法尼酯X受体；GAPDH为甘油醛－3－磷酸脱氢酶
表3 2组肝硬化大鼠肝切除术后肝脏再生指标的比较(±s)
组别 鼠数(只) MI(%) PCNA标记指数(%) 细胞核DNA含量(%)
实验组 12 2.89±0.67 4.76±0.89 8.82±2.12
对照组 12 1.12±0.34 2.46±0.68 3.98±1.16
t值 ? 4.688 5.069 6.858
P值 ? 0.003 0.006 0.005
[1]
鲁育民. 胆汁酸核受体FXR与肝再生[J]. 现代医药卫生，2012, 28(23):3594-3596.
[2]
晁祥嵩，国麟祺，丁隆，等. 肝再生过程中胆汁酸对FXR的影响[J]. 黑龙江医药科学，2014, 37(3):23-25.
[3]
展翰翔，张太平，赵玉沛，等. 核受体FXR在胆汁代谢相关脏器疾病中的调控机制及研究进展[J]. 国际外科学杂志，2016, 37(11):777-780.
[4]
丁隆，杨宇，曲义坤，等. 胆酸对大鼠肝部分切除术后肝细胞脂质代谢及法尼醇X受体表达的影响[J]. 中国老年学杂志，2015, 3(7):1876-1878.
[5]
Fausto N, Campbell JS, Riehle KJ. Liver regeneration[J]. J Hepatol, 2012, 57(3):692-694.
[6]
Michalopoulos GK. Liver regeneration after partial hepatectomy：critical analysis of mechanistic dilemmas[J]. Am J Pathol, 2010, 176(1/2):2-13.
[7]
Huang W, Ma K, Zhang J, et al. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration[J]. Science, 2006, 312(5771):233-236.
[8]
Parks DJ, Blanchard SG, Bledsoe PK, et al. Bile acids：natural ligands for an orphan nuclear receptor[J]. Science, 1999, 284(5418):1365-1368.
[9]
Wang H, Chen J, Hollister k, et al. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR[J]. Mol Cell, 1999, 3(5):534-553.
[10]
Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acid[J]. Science, 1999, 284(5418):1362-1365.
[11]
Cai SY, Xiong L, Wray CG, et al. The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution[J]. Am J Physiol Regul Integr Comp Physiol, 2007, 293(3):1400-1409.
[12]
Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation[J]. J Biol Chem, 2003, 278(1):104-110.
[13]
Lambert G, Amar MJ, Guo G, et al. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis[J]. J Biol Chem, 2003, 278(4):2563-2570.
[14]
Sinal CJ, Tohkin M, Miyata M, et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis[J]. Cell, 2000, 102(6):731-744.
[15]
Wang YD, Chen WD, Moore DD, et al. FXR: a metabolic regulator and cell protector[J]. Cell Res, 2008, 18(11):1087-1095.
[16]
Wang YD, Yang F, Chen WD, et al. Farnesoid X receptor protects liver cells from apoptosis induced by serum deprivation in vitro and fasting in vivo[J]. Mol Endocrinol, 2008, 22(7):1622-1632.
[17]
Dawson PA, Lan T, Rao A. Bile acid transporters[J]. J Lipid Res, 2009, 50(12):2340-2357.
[18]
Sievnen E. Exploitation of bile acid transport systems in prodrug design[J]. Molecules, 2007, 12(8):1859-1889.
[19]
Mitro N, Godio C, De Fabiani E, et al. Insights in the regulation of cholesterol 7alpha-hydroxylase gene reveal a target for modulating bile acid synthesis[J]. Hepatology, 2007, 46(3):885-897.
[20]
Jia C. Advances in the regulation of liver regeneration[J]. Expert Rev Gastroenterol Hepatol, 2011, 5(1):105-121.
[1] 叶晓琳, 刘云飞, 庞明泉, 王海久, 任利, 侯立朝, 于文昊, 王志鑫, 樊海宁. 肝再生细胞来源及调控机制的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 96-99.
[2] 王春荣, 陈姜, 喻晨. 循Glisson蒂鞘外解剖、Laennec膜入路腹腔镜解剖性左半肝切除术临床应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 37-40.
[3] 李建美, 邓静娟, 杨倩. 两种术式联合治疗肝癌合并肝硬化门静脉高压的安全性及随访评价[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 41-44.
[4] 吴方园, 孙霞, 林昌锋, 张震生. HBV相关肝硬化合并急性上消化道出血的危险因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 45-47.
[5] 索郎多杰, 高红桥, 巴桑顿珠, 仁桑. 腹腔镜下不同术式治疗肝囊型包虫病的临床疗效分析[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 670-673.
[6] 汤海琴, 郭秀枝, 朱晓素, 赵世娣. “隧道法”腹腔镜解剖性左半肝切除术的临床安全性研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 674-677.
[7] 莫闲, 杨闯. 肝硬化患者并发门静脉血栓危险因素的Meta分析[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 678-683.
[8] 唐浩, 梁平, 徐小江, 曾凯, 文拨辉. 三维重建指导下腹腔镜右半肝加尾状叶切除治疗Bismuth Ⅲa型肝门部胆管癌的临床研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 688-692.
[9] 段文忠, 白延霞, 徐文亭, 祁虹霞, 吕志坚. 七氟烷和丙泊酚在肝切除术中麻醉效果比较Meta分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 640-645.
[10] 韩宇, 张武, 李安琪, 陈文颖, 谢斯栋. MRI肝脏影像报告和数据系统对非肝硬化乙肝患者肝细胞癌的诊断价值[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 669-673.
[11] 唐灿, 李向阳, 秦浩然, 李婧, 王天云, 柯阳, 朱红. 原发性肝脏神经内分泌肿瘤单中心12例诊治与疗效分析[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 674-680.
[12] 秦维, 王丹, 孙玉, 霍玉玲, 祝素平, 郑艳丽, 薛瑞. 血清层粘连蛋白、Ⅳ型胶原蛋白对代偿期肝硬化食管胃静脉曲张出血的预测价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 447-451.
[13] 张雯, 宋牡丹, 邓雪婷, 张云. 强化营养支持辅助奥曲肽治疗肝硬化合并食管胃底静脉曲张破裂出血的疗效及再出血危险因素[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 456-460.
[14] 朱翔宇, 王建美, 张辉, 叶红英. 无创左心室压力-应变循环技术在左心室功能参数与肝硬化的相关性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 494-498.
[15] 孔凡彪, 杨建荣. 肝脏基础疾病与结直肠癌肝转移之间关系的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(07): 818-822.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号