非酒精性脂肪性肝病肝纤维化进展与内皮素-1/一氧化氮的关系

李品桦; 刘旭东; 黄露; 朱沪敏; 吴铁雄; 庞华珍

doi:10.3969/j.issn.1001-5256.2021.11.015

非酒精性脂肪性肝病肝纤维化进展与内皮素-1/一氧化氮的关系

DOI: 10.3969/j.issn.1001-5256.2021.11.015

1.
广西中医药大学研究生学院，南宁 530001
2.
广西中医药大学附属瑞康医院肝病科，南宁 530011

基金项目:

广西科学基金项目 (AB18221009);

广西中医药大学岐黄工程高层次人才团队培育项目 (2021007);

2019年广西一流学科建设课题 (2019XK139);

2019年中医药传承与创新人才培养平台建设项目 (National Traditional Chinese Medicine Education Letter No.41, 2019);

国家自然科学基金 (81473532)

详细信息

通信作者:
刘旭东，lxdlhx@163.com

中图分类号: R575.2; R575.5
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出版历程
- 收稿日期: 2021-03-13
- 录用日期: 2021-04-25
- 出版日期: 2021-11-20

Association between liver fibrosis progression and endothelin-1/nitric oxide in patients with nonalcoholic fatty liver disease

1.
Graduate School, Guangxi University of Chinese Medicine, Nanning 530001, China
2.
Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, China

Research funding:

Guangxi Science Foundation Project (AB18221009);

High-Level Talent Team Cultivation Project of the Qihuang Project of Guangxi University of Traditional Chinese Medicine (2021007);

Guangxi First-Class Discipline Construction Project in 2019 (2019XK139);

Traditional Chinese Medicine Inheritance and Innovation Talents Training Platform Construction Project in 2019 (National Traditional Chinese Medicine Education Letter No.41, 2019);

National Natural Science Foundation of China (81473532)

摘要

摘要: 目的探讨非酒精性脂肪性肝病(NAFLD)肝纤维化进展是否会对内皮功能产生影响，以早期发现纤维化进展对内皮功能障碍所致心血管疾病的预警。方法选取2019年4月—2020年10月就诊于广西中医药大学附属瑞康医院肝病科门诊/住院，经超声诊断为脂肪肝且符合NAFLD诊断标准的患者280例，收集并记录患者的一般资料及各血清学指标。对超声诊断的NAFLD患者进行FibroTouch技术检测，分别记录其脂肪衰减度(FAP)及肝硬度值(LSM)，根据LSM将研究对象分为非进展期纤维化组(LSM＜11 kPa，n=239) 和进展期纤维化组(LSM≥11 kPa，n=41)，比较分析NAFLD肝纤维化进展与内皮素-1(ET-1)、一氧化氮(NO)的关系。计量资料两组间比较采用t检验或Mann-Whitney U检验，相关性分析用Spearman分析方法。结果非进展期纤维化组和进展期纤维化组中ET-1(Z=-0.190, P=0.849)、NO(Z=-1.509, P=0.131)的表达水平比较差异无统计学意义。BMI、ALT、AST、GGT、TG、HDL-C在两组间比较差异均有统计学意义(Z值分别为-3.977、-4.162、-3.471、-3.201、-3.202、-3.311，P值均＜0.05)。Spearman分析示，LSM与ET-1、NO、NO/ET-1无相关性(r_s值分别为-0.046、0.086和0.104，P值均＞0.05)。进一步分析了ET-1、NO与血脂、肝功能等指标的相关性，结果显示ET-1与年龄、NO、ALT、AST、GGT、TC、TG、HDL-C、LDL-C、FAP、BMI均不相关(P值均＞0.05)，NO与年龄、ET-1、ALT、AST、GGT、TC、TG、HDL-C、LDL-C、FAP、BMI各指标间也并无相关性(P值均＞0.05)。结论在本研究中，NAFLD肝纤维化进展对ET-1、NO无影响，提示纤维化进展可能对内皮功能无影响。
- 肝硬化 /
- 非酒精性脂肪性肝病 /
- 内皮缩血管肽1 /
- 一氧化氮
Abstract: Objective To investigate whether the progression of liver fibrosis affects endothelial function in patients with nonalcoholic fatty liver disease (NAFLD), and to early identify the warning of cardiovascular diseases caused by endothelial dysfunction by liver fibrosis progression. Methods A total of 280 patients who attended the outpatient service or were hospitalized in Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, from April 2019 to October 2020 were enrolled, and they were diagnosed with fatty liver disease by ultrasound and met the diagnostic criteria for NAFLD. General information and related serological markers were collected and recorded. FibroTouch technique was performed for the NAFLD patients diagnosed by ultrasound to record their fat attenuation parameter (FAP) and liver stiffness measurement (LSM), and according to LSM, the patients were divided into non-progressive fibrosis group (239 patients with LSM < 11 kPa) and progressive fibrosis group (41 patients with LSM ≥11 kPa) to analyze the association between liver fibrosis progression and endothelin-1 (ET-1)/nitric oxide (NO) in NAFLD. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the Spearman method was used for correlation analysis. Results There were no significant differences between the non-progressive fibrosis group and the progressive fibrosis group in the expression levels of ET-1(Z=-0.190, P=0.849) and NO(Z=-1.509, P=0.131), and there were significant differences between the two groups in body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) (Z=-3.977, -4.162, -3.471, -3.201, -3.202, and -3.311, all P < 0.05). The Spearman analysis showed that LSM was not correlated with ET-1, NO, and NO/ET-1 (r_s=-0.046, 0.086, and 0.104, all P > 0.05). Further analysis of the correlation of ET-1 and NO with each index showed that ET-1 was not correlated with age, NO, ALT, AST, GGT, total cholesterol, TG, HDL-C, low-density lipoprotein cholesterol (LDL-C), FAP, and BMI (r_s=-0.017, 0.054, -0.067, -0.016, -0.031, 0.004, 0.051, -0.084, -0.030, 0.080, and 0.044, all P > 0.05), and NO was not correlated with age, ET-1, ALT, AST, GGT, total cholesterol, TG, HDL-C, LDL-C, FAP, and BMI (r_s=0.004, 0.054, 0.011, 0.052, 0.004, -0.051, -0.052, -0.012, -0.076, -0.013, and -0.021, all P > 0.05). Conclusion This study shows that liver fibrosis progression in NAFLD has no impact on ET-1 and NO, suggesting that fibrosis progression may have no influence on endothelial function.
- Liver Cirrhosis /
- Non-Alcoholic Fatty Liver Disease /
- Endothelin-1 /
- Nitric Oxide

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表 1 两组NAFLD患者ET-1、NO等血清学指标及一般资料比较

指标	非进展期纤维化组 (n=239)	进展期纤维化组 (n=41)	统计值	P值
年龄(岁)	46.80±12.27	47.39±13.16	t=-0.280	0.577
NO(μmol/L)	36.65(23.47~55.06)	43.96(33.25~57.66)	Z=-1.509	0.131
ET-1(pg/mL)	56.41(39.10~77.17)	57.71(39.98~73.49)	Z=-0.190	0.849
ALT(U/L)	26(18~39)	46(31~77)	Z=-4.162	＜0.001
AST(U/L)	24(18~32)	34(22~61)	Z=-3.471	0.001
GGT(U/L)	36(25~56)	47(35~77)	Z=-3.201	0.001
TC(mmol/L)	5.00±1.04	4.70±1.31	t=1.601	0.083
TG(mmol/L)	1.78(1.26~2.61)	1.29(0.92~1.82)	Z=-3.202	0.001
HDL-C(mmol/L)	1.13(1.00~1.35)	0.97(0.81~1.17)	Z=-3.311	0.001
LDL-C(mmol/L)	2.87±0.89	2.78±0.93	t=0.639	0.725
FAP(db/m)	258.56±36.98	272.90±36.55	t=-2.297	0.552
BMI(kg/m²)	26.39(24.44~28.69)	27.39(26.27~31.51)	Z=-3.977	＜0.001
NO/ET-1	0.70(0.43~1.05)	0.75(0.54~1.18)	Z=-1.291	0.197

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表 2 ET-1、NO及NO/ET-1与LSM的相关性分析

指标	r_s值	P值
NO	0.086	0.153
ET-1	-0.046	0.443
NO/ET-1	0.104	0.082

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表 3 ET-1与各指标的相关性分析

指标	ET-1		NO
指标	r_s值	P值	r_s值	P值
年龄	-0.017	0.771	0.004	0.941
NO/ET-1	0.054	0.369	0.054	0.369
ALT	-0.067	0.265	0.011	0.860
AST	-0.016	0.788	0.052	0.383
GGT	-0.031	0.603	0.004	0.951
TC	0.004	0.952	-0.051	0.399
TG	0.051	0.394	-0.052	0.389
HDL-C	-0.084	0.162	-0.012	0.729
LDL-C	-0.030	0.620	-0.076	0.205
FAP	0.080	0.180	-0.013	0.832
BMI	0.044	0.466	-0.021	0.729

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