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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
Association between microRNA-155/SH2-containing inositol phosphatase-1 and cardiovascular events in patients with nonalcoholic fatty liver disease
文章发布日期:2020年06月01日  来源:  作者:王凡,孙武,马玉林,等  点击次数:154次  下载次数:33次

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【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、HDL-C、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-1 mRNA相对表达量明显低于对照组,且miR-155/SHIP-1值、心血管事件发生率均明显高于对照组,差异均有统计学意义(t值分别为6.617、9.323、6.668、8.633、4.285、22.099、24.093、20.438、12.366、6.515、18.893、18.411、29.967,χ2=10.476,P值均<0.01)。根据患者miR-155/SHIP-1值将患者分为3组,3组间BMI、FPG、TC、TG、LDL-C、HDL-C、ALT、AST、GGT、TBil以及心血管事件发生率比较,差异均有统计学意义(H值分别为20.923、7.936、6.256、16.181、21.572、8.435、18.912、22.869、7.665、18.657、9.701,P值均<0.05)。miR-155/SHIP-1值与BMI、FPG、TC、TG、LDL-C、ALT、AST、GGT、TBil呈显著正相关(r值分别0.297、0.317、0.332、0.327、0.286、0.334、0.352、0.342、0.350,P值均<0.001),与HDL-C呈显著负相关(r=-0.279,P<0.001)。发生心血管事件患者miR-155/SHIP-1值(3.642±1.082)明显高于未发生心血管事件患者(2.237±0.703),差异有统计学意义(t=11.104,P<0.05); miR-155/SHIP-1值预测NAFLD患者发生心血管事件的ROC曲线下面积为0.902。结论 NAFLD患者糖脂代谢及肝功能异常与miR-155/SHIP-1表达密切相关,且miR-155/SHIP-1值对NAFLD患者发生心血管事件具有一定的预测价值。
【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.
【关键字】: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
【Key words】:non-alcoholic fatty liver disease; microRNAs; phosphoinositide phos;phatases cardiovascular diseases
【引证本文】:WANG F, SUN W, MA YL, et al. Association between microRNA-155/SH2-containing inositol phosphatase-1 and cardiovascular events in patients with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(6): 1325-1329. (in Chinese)
王凡, 孙武, 马玉林, 等. 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[J]. 临床肝胆病杂志, 2020, 36(6): 1325-1329.

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