微小RNA-155/含有SH2结构的5肌醇磷酸酶-1与非酒精性脂肪性肝病患者发生心血管事件的相关性

王凡; 孙武; 马玉林; 蒋红君

doi:10.3969/j.issn.1001-5256.2020.06.027

微小RNA-155/含有SH2结构的5肌醇磷酸酶-1与非酒精性脂肪性肝病患者发生心血管事件的相关性

DOI: 10.3969/j.issn.1001-5256.2020.06.027

云南省第一人民医院(昆明理工大学附属医院)检验科

基金项目:

国家自然科学基金(81960037)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 1042
- HTML全文浏览量: 18
- PDF下载量: 149
- 被引次数: 12
出版历程
- 出版日期: 2020-06-20

Association between microRNA-155/SH2-containing inositol phosphatase-1 and cardiovascular events in patients with nonalcoholic fatty liver disease

Research funding:

摘要

摘要:
目的分析微小RNA-155（microRNA,miR-155）-155/含有SH2结构的5肌醇磷酸酶-1（SHIP-1）与非酒精性脂肪性肝病（NAFLD）患者发生心血管事件的相关性。方法选取2018年3月-2019年7月云南省第一人民医院收治的NAFLD患者104例,以及同期接受健康体检志愿者110例作为对照组。检测两组受试者BMI、血压及空腹血糖（FPG）、TC、TG、LDL-C、HDLC、ALT、AST、GGT、TBil等指标,采用荧光定量PCR法检测两组受试者外周血miR-155及SHIP-1 mRNA表达。计量资料2组间比较采用t检验;计数资料组间比较采用χ2检验;等级资料组间比较采用Kruskal-Wallis H秩和检验。相关性检验采用Pearson分析。采用受试者工作特征曲线（ROC曲线）分析miR-155/SHIP-1值对患者心血管事件的预测价值。结果 NAFLD组患者BMI、FPG、TC、TG、LDL-C、ALT、AST、GGT、TBil水平均明显高于对照组,HDL-C水平明显低于对照组,miR-155 mRNA相对表达量明显高于对照组,SHIP...
- 非酒精性脂肪性肝病 /
- 微RNAs /
- 磷脂酰肌醇磷酸酶类 /
- 心血管疾病
Abstract:
Objective To investigate the association between microRNA-155( miR-155)/SH2-containing inositol phosphatase-1( SHIP-1) and cardiovascular events in patients with nonalcoholic fatty liver disease( NAFLD). Methods A total of 104 patients with NAFLD who were admitted to our hospital from March 2018 to July 2019 were enrolled as NAFLD group,and 110 healthy volunteers who underwent physical examination in our hospital during the same period of time were enrolled as control group. Related indices were measured,including body mass index( BMI),blood pressure,fasting plasma glucose( FPG),total cholesterol( TC),triglyceride( TG),low-density lipoprotein cholesterol( LDL-C),high-density lipoprotein cholesterol( HDL-C),alanine aminotransferase( ALT),aspartate aminotransferase( AST),gamma-glutamyl transpeptidase( GGT),and total bilirubin( TBil),and quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SHIP-1 in peripheral blood. The t-test was used for comparison of continuous data between two groups,the chi-square test was used for comparison of categorical data between two groups,and the Kruskal-Wallis H test was used for comparison of ranked data between groups. A Pearson correlation analysis was performed,and the receiver operating characteristic( ROC) curve was used to investigate the value of miR-155/SHIP-1 ratio in predicting cardiovascular events. Results Compared with the control group,the NAFLD group had significantly higher levels of BMI,FPG,TC,TG,LDL-C,ALT,AST,GGT,and TBil and a significantly lower level of HDL-C,as well as significantly higher relative mRNA expression of miR-155,significantly lower relative mRNA expression of SHIP-1,and a significantly higher incidence rate of cardiovascular events( t = 6. 617,9. 323,6. 668,8. 633,4. 285,22. 099,24. 093,20. 438,12. 366,6. 515,18. 893,18. 411,and 29. 967,χ2= 10. 476,all P < 0. 01). The patients were divided into three groups according to miR-155/SHIP-1 ratio,there were significant differences between the three groups in BMI,FPG,TC,TG,LDL-C,HDL-C,ALT,AST,GGT,TBil,and incidence rate of cardiovascular events( H = 20. 923,7. 936,6. 256,16. 181,21. 572,8. 435,18. 912,22. 869,7. 665,18. 657,and 9. 701,all P < 0. 05). The miR-155/SHIP-1 ratio was significantly correlated with BMI,FPG,TC,TG,LDL-C,HDL-C,ALT,AST,GGT,and TBil( r = 0. 297,0. 317,0. 332,0. 327,0. 286,-0. 279,0. 334,0. 352,0. 342,and 0. 350,all P < 0. 001). The patients with cardiovascular events had a significantly higher miR-155/SHIP-1 ratio than those without cardiovascular events( 3. 642 ± 1. 082 vs 2. 237 ± 0. 703,t = 11. 104,P < 0. 05),and the miR-155/SHIP-1 ratio had an area under the ROC curve of 0. 902 in predicting cardiovascular events in patients with NAFLD. Conclusion Abnormal glycolipid metabolism and liver function in patients with NAFLD are closely associated with the expression of miR-155/SHIP-1,and miR-155/SHIP-1 ratio has a certain value in predicting cardiovascular events in patients with NAFLD.
- non-alcoholic fatty liver disease /
- microRNAs /
- phosphoinositide phosphatases /
- cardiovascular diseases

HTML全文

参考文献(20)

[1] SWEET PH,KHOO T,NGUYEN S. Nonalcoholic fatty liver disease[J]. Prim Care,2017,44(4):599-607.

[2] WILD SH,WALKER JJ,MORLING JR,et al. Cardiovascular disease,cancer,and mortality among people with type 2 diabetes and alcoholic or nonalcoholic fatty liver disease hospital admission[J]. Diabetes Care,2018,41(2):341-347.

[3] FRANCQUE SM,van der GRAAFF D,KWANTEN WJ. Nonalcoholic fatty liver disease and cardiovascular risk:Pathophysiological mechanisms and implications[J]. J Hepatol,2016,65(2):425-443.

[4] BREA A,PUZO J. Non-alcoholic fatty liver disease and cardiovascular risk[J]. Int J Cardiol,2013,167(4):1109-1117.

[5] TRIVEDI I,RINELLA ME. NAFLD and cardiovascular disease:Can the real association be determined?[J]. Curr Hepatol Rep,2014,13(2):130-141.

[6] LISA W,SLACK FJ. miR-155 as a novel clinical target for hematological malignancies[J]. Carcinogenesis,2020,41(1):2-7.

[7] SCHWIMMER JB,BEHLING C,ANGELES JE,et al. Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease[J].Hepatology,2017,66(5):1474-1485.

[8] National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association.Guidelines for diagnosis and treatment of nonalcoholic fatty liver disease[J]. J Clin Hepatol,2010,26(2):120-124.(in Chinese)中华医学会肝病学分会脂肪肝和酒精性肝病学组．非酒精性脂肪性肝病诊疗指南[J]．临床肝胆病杂志，2010,26(2):120-124.

[9] HUDERT CA,TZSCHTZSCH H,GUO J,et al. US time-harmonic elastography:Detection of liver fibrosis in adolescents with extreme obesity with nonalcoholic fatty liver disease[J].Radiology,2018,288(1):99-106.

[10] PISETTA C,PELIZZARI G,PIGOZZI MG,et al. Non-alcoholic fatty liver disease and cardiovascular risk[J]. J Hypertens,2019,37:e304.

[11] MORELLO E,SUTTI S,FOGLIA B,et al. Hypoxia-inducible factor 2αdrives nonalcoholic fatty liver progression by triggering hepatocyte release of histidine-rich glycoprotein[J].Hepatology,2018,67(6):2196-2214.

[12] TARGHER G,DAY CP,BONORA E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease[J].New Engl J Med,2010,363(14):1341-1350.

[13] SU L,ZHANG YW,WANG Z. Proliferation inhibition and proapoptotic effects of shikonin on human leukemia MV4-11 cells[J]. J Jilin Univ(Med Edit),2020,46(1):96-101.(in Chinese)苏龙，张云蔚，王卓．紫草素对人白血病MV4-11细胞的增殖抑制和促凋亡作用[J]．吉林大学学报(医学版)，2020,46(1):96-101.

[14] ZHANG L,GAO XF,WANG YH. The expression of chemerin and the influence of sitagliptin on its expression in non-alcoholic fatty liver disease rats complicated with prediabetes[J].Natl Med J China,2018,98(30):2407-2413.(in Chinese)张莉，高旭峰，王玉环．非酒精性脂肪肝并糖尿病前期chemerin表达及西格列汀对其表达的影响[J]．中华医学杂志，2018,98(30):2407-2413.

[15] STOKES CS,LAMMERT F,KRAWCZYK M. Short-term dietary interventions for the management of nonalcoholic fatty liver[J]. Curr Med Chem,2019,26(19):3483-3496.

[16] HU MQ,XU YQ,ZHANG T,et al. Research advances in noninvasive diagnostic methods for nonalcoholic steatohepatitis[J]. J Clin Hepatol,2017,33(12):2288-2291.(in Chinese)胡梦琪，徐有青，张涛，等．非酒精性脂肪性肝炎的无创诊断方法[J]．临床肝胆病杂志，2017,33(12):2288-2291.

[17] ESTES C,RAZAVI H,LOOMBA R,et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease[J]. Hepatology,2018,67(1):123-133.

[18] YOUNOSSI ZM. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis:Implications for liver transplantation[J].Liver Transpl,2018,24(2):166-170.

[19] CHEN B,LIN HX. Intervention of polyene phosphatidylcholine on mice with nonalcoholic fatty liver disease and its effect on hepatic zinc finger protein A20 expression[J]. Chin J Clin Pharmacol Ther,2018,34(11):1353-1356.(in Chinese)陈彬，林海雪．多烯磷脂酰胆碱对非酒精性脂肪肝小鼠的干预及其对肝锌指蛋白A20表达的影响[J]．中国临床药理学杂志，2018,34(11):1353-1356.

[20] DING J,ZHANG B,WANG PJ,et al. Analysis on mechanisms and medication rules of herbal prescriptions for nonalcoholic fatty liver disease based on methods of data mining and biological information[J]. China J Chin Mater Med,2019,44(8):1689-1695.(in Chinese)丁静，张斌，王培劫，等．基于数据挖掘和生物信息分析探讨非酒精性脂肪肝用药规律及作用机制[J]．中国中药杂志，2019,44(8):1689-1695.

施引文献

期刊类型引用(6)

1.	朱亭亭，陈逸云，谢帆慈，李正鑫. 无创评估肝纤维化逆转研究进展. 实用肝脏病杂志. 2025(02): 169-172 . 百度学术
2.	巴图德力根，韩志强，韩格根套丽，徐艳华，牧仁，安达. 德都红花-7味散及其主要成分对肝纤维化小鼠CCR1、DNMT1蛋白的作用研究. 中国临床药理学杂志. 2024(07): 1004-1008 . 百度学术
3.	张永，李艺，张欢. 复肝消积汤联合恩替卡韦治疗乙肝肝硬化代偿期的临床观察. 中国中西医结合消化杂志. 2023(02): 100-103+109 . 百度学术
4.	李定富，唐换灵，黄健，王秀琪. 血PⅢP、LN、HA水平与慢性肝炎程度、肝纤维化分期及炎症活动度分级的关系. 临床和实验医学杂志. 2022(10): 1119-1121 . 百度学术
5.	何杰，余松，董金玲，陈燕. 复元活血汤治疗肝硬化疗效观察及对肝脏纤维化的影响. 新中医. 2021(18): 29-32 . 百度学术
6.	刘沁雨，常越，张青，丁玉平，李海. 高尔基体蛋白73对抗病毒治疗慢性乙型肝炎患者代偿期肝硬化的诊断价值. 解放军医药杂志. 2020(03): 86-91 . 百度学术