长链非编码 RNA NEAT1、miRNA-182-5p与 2 型糖尿病患者肝纤维化风险的相关性研究
orrelation of LncRNA NEAT1 and miRNA-182-5p with the Risk of Liver Fibrosis in Patients with Type 2 Diabetes Mellitus
背景 随着慢性代谢性疾病的发病率逐年上涨,已威胁全民健康,目前非编码RNA与内分泌代谢相关疾病的研究已成为国内外研究热点,其中长链非编码RNA核富集丰富转录物1(lncRNA NEAT1)及微小RNA(miRNA)-182-5p在2型糖尿病(T2DM)合并代谢相关脂肪性肝病(MAFLD)中的研究鲜有报道。目的 探讨T2DM合并MAFLD患者lncRNA NEAT1、miRNA-182-5p在肝纤维化发生发展中的机制及临床意义。方法 纳入2021年10月—2022年6月在内蒙古科技大学包头医学院第一附属医院内分泌科就诊的T2DM患者236例为研究对象,同时纳入49名健康人群为健康对照组。收集研究对象一般资料与实验室检测结果。测定内脏脂肪面积(VFA)、皮下脂肪面积(SFA)。采集研究对象外周血,测定lncRNA NEAT1、miRNA-182-5p。将T2DM患者其分为T2DM合并非MAFLD组(n=82)与T2DM合并MAFLD组(n=154)。进一步根据肝纤维化指数(FIB-4)将T2DM合并MAFLD组分为肝纤维化低危亚组(n=55),肝纤维化中危亚组(n=69),肝纤维化高危亚组(n=30)。此外选择健康人群体检作为对照组(n=49)。用Sperman秩相关分析探究肝纤维化高危亚组lncRNA NEAT1、miRNA-182-5p表达水平的相关性,采用多因素有序Logistic回归分析探究肝纤维化风险的影响因素。结果 健康对照组年龄、颈围(NC)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)低于T2DM合并MAFLD组、T2DM不合并MAFLD组,白蛋白(Alb)高于T2DM合并MAFLD组、T2DM不合并MAFLD组,差异有统计学意义(P<0.05);T2DM合并MAFLD组BMI、腰围(WC)、VFA、SFA、稳态模型评估胰岛素抵抗指数(HOMA-IR)、三酰甘油(TG)、血尿酸(SUA)、lncRNA NEAT1高于健康对照组、T2DM不合并MAFLD组,血小板计数(PLT)低于健康对照组、T2DM不合并MAFLD组,总胆固醇(TC)低于健康对照组,差异有统计学意义(P<0.05);T2DM不合并MAFLD组HOMA-IR、lncRNA NEAT1高于健康对照组,miRNA-182-5p高于健康对照组、T2DM合并MAFLD组,丙氨酸氨基转移酶(ALT)、天冬氨酸基转移酶(AST)低于健康对照组、T2DM合并MAFLD组,差异有统计学意义(P<0.05)。肝纤维化低危亚组VFA、SFA、AST、lncRNA NEAT1低于肝纤维化中危亚组、肝纤维化高危亚组,PLT、miRNA-182-5p高于肝纤维化中危亚组、肝纤维化高危亚组,BMI、WC、NC低于肝纤维化高危亚组,TC高于肝纤维化高危亚组,差异有统计学意义(P<0.05);肝纤维化中危亚组PLT、miRNA-182-5p高于肝纤维化高危亚组,AST、lncRNA NEAT1低于肝纤维化高危亚组,差异有统计学意义(P<0.05)。Spearman秩相关分析结果显示,肝纤维化高危亚组患者lncRNA NEAT1与miRNA-182-5p呈明显负相关(rs=-0.438,P<0.05)。多因素有序Logistic回归分析结果显示,lncRNA NEAT1〔OR=1.326,95%CI(1.087,1.616)〕、VFA〔OR=1.019,95%CI(1.006,1.033)〕、miRNA-182-5p〔OR=0.083,95%CI(0.027,0.257)〕、PLT〔OR=0.956,95%CI(0.942,0.970)〕、AST〔OR=1.048,95%CI(1.022,1.075)〕是T2DM合并MAFLD患者肝纤维化风险的影响因素。结论 外周血lncRNA NEAT1、miRNA-182-5p与T2DM合并MAFLD患者并发肝纤维化密切相关,为该病的早期预测及诊治提供了新的依据。
BackgroundWith the incidence of chronic metabolic diseases rising by year which has threatened the national healththe study of non-coding RNA and endocrine metabolism-related diseases has become a research hotspot at home and abroadwhile lncRNA NEAT1 and miRNA-185-5p in type 2 diabetes mellitusT2DMcombined with metabolicrelated fatty liver diseaseMAFLDhas been rarely reported. ObjectiveTo investigate the mechanism and clinical significance of lncRNA NEAT1 and miRNA-182-5p in the development of liver fibrosis in T2DM patients with MAFLD. MethodsA total of 236 T2DM patients admitted to the endocrinology department of the First Affiliated Hospital of Baotou Medical CollegeInner Mongolia University of Science and Technology from October 2021 to June 2022 were included as the study subjectsand 49 healthy people were included as the healthy control group. General information and laboratory test results of the subjects were collected. Visceral fat areaVFAand subcutaneous fat areaSFAwere measured. Peripheral blood was collected and lncRNA NEAT1 miRNA-182-5p were determined. T2DM patients were divided into the T2DM with non-MAFLD groupn=82and T2DM with MAFLD groupn=154. T2DM with MAFLD group was further divided into the low-risk subgroupn=55medium-risk subgroupn=69and high-risk subgroupn=30 according to the liver fibrosis indexFIB-4. In additionhealthy people were selected as the healthy control groupn=49. Sperman rank correlation analysis was used to explore the correlation of lncRNA NEAT1 and miRNA-182-5p expression levels in the high-risk subgroup of liver fibrosisand multilevel ordinal logistic regression was used to explore the influencing factors of liver fibrosis risk. ResultAgeneck circumferenceNCfasting blood glucoseFPGand glycosylated hemoglobinHbA1cin the healthy control group were lower than those in the T2DM with non-MAFLD and T2DM with MAFLD groupsthe albuminAlbin the healthy control group was higher than that in the T2DM with non-MAFLD and T2DM with MAFLD groups the difference was statistically significant P<0.05. BMIwaist circumferenceWCVFASFAhomeostatic model assessment for insulin resistanceHOMA-IRtriglycerideTG serum uric acidSUAand lncRNA NEAT1 in the T2DM with MAFLD group were higher than those in the healthy control group and T2DM with non-MAFLD group platelet countPLTwas lower than that of the healthy control group and T2DM with non-MAFLD grouptotal cholesterolTCwas lower than that of the healthy control groupthe difference was statistically significantP<0.05. HOMA-IR and lncRNA NEAT1 in the T2DM with non-MAFLD groups were higher than those in the healthy control groupmiRNA-182-5p was higher than that in the healthy control group and T2DM with MAFLD group alanine aminotransferaseALTand aspartate transferaseASTwere lower than those in the healthy control group and T2DM with MAFLD groupand the difference was statistically significantP<0.05. VFASFAAST and lncRNA NEAT1 in the low-risk subgroup were lower than those in the medium-risk subgroup and high-risk subgroupPLT and miRNA-182-5p were higher than those in the medium-risk subgroup and high-risk subgroupBMIWC and NC were lower than those in the highrisk subgroup TC was higher than that in the high-risk group of liver fibrosisthe difference was statistically significantP<0.05. PLT and miRNA-182-5p in the medium-risk subgroup were higher than the high-risk subgroupAST and lncRNA NEAT1 were lower than those in the high risk groupand the difference was statistically significantP<0.05. Spearman rank correlation analysis showed that lncRNA NEAT1 was significantly negatively correlated with miRNA-182-5p in the high-risk subgroup of liver fibrosisrs=-0.438P<0.05. The results of multilevel ordinal logistic regression analysis showed that lncRNA NEAT1OR=1.32695%CI1.0871.616VFAOR=1.01995%CI1.0061.033miRNA-182-5pOR=0.08395%CI0.0270.257PLTOR=0.95695%CI0.9420.970ASTOR=1.04895%CI1.0221.075were the risk factors of liver fibrosis in T2DM patients with MAFLD. ConclusionPeripheral blood lncRNA NEAT1 and miRNA-182-5p are closely related to the complicated liver fibrosis in T2DM patients with MAFLDproviding a new basis for the early prediction diagnosis and treatment of the disease.
贺佳、魏枫、李永平、韶龙格、吴亚玲、刘美岚
10.12114/j.issn.1007-9572.2023.0368
内科学基础医学临床医学
2 型糖尿病代谢相关脂肪性肝病核富集丰富转录物 1微小 RNA-182-5p肝纤维化影响因素分析
ype 2 diabetes mellitusMetabolic-related fatty liver diseaseNEAT1miRNA-182-5pHepatic fibrosisRoot cause analysis
贺佳,魏枫,李永平,韶龙格,吴亚玲,刘美岚.长链非编码 RNA NEAT1、miRNA-182-5p与 2 型糖尿病患者肝纤维化风险的相关性研究[EB/OL].(2023-07-24)[2025-08-19].https://chinaxiv.org/abs/202307.00702.点此复制
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