NASH患者外周血乏氧诱导因子1a-反义RNA 1和自噬基因Beclin1变化及其临床意义*

doi:10.3969/j.issn.1672-5069.2022.04.016

摘要/Abstract

摘要： 目的研究非酒精性脂肪性肝炎(NASH)患者外周血单个核细胞(PBMC)乏氧诱导因子1a-反义RNA 1(HIF1a-AS1)和血清自噬基因beclin1水平变化及其临床意义。方法 2019年1月～2021年4月我院诊治的NASH患者118例(早期纤维化、进展期纤维化和肝硬化分别为43例、46例和29例)和同期健康体检者118例,使用全自动生化分析仪检测空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平,采用实时荧光定量PCR法检测PBMC HIF1a-AS1水平,采用ELISA法检测血清beclin1水平。结果 NASH患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(5.9±1.6)mmol/L、(6.2±0.5)mmol/L、(2.4±0.6)mmol/L、(3.7±0.9)mmol/L、(1.9±0.2)和(5.7±1.9)ng/mL,显著高于健康者【分别为(4.8±0.7)mmol/L、(5.3±0.3)mmol/L、(1.3±0.3)mmol/L、(2.3±0.6)mmol/L、(1.0±0.1)和(4.1±1.5)ng/mL,P＜0.05】,而血清HDL-C水平为(1.2±0.2)mmol/L,显著低于健康者【(1.4±0.3)mmol/L,P＜0.05】;肝硬化患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(6.8±2.0)mmol/L、(6.8±0.8)mmol/L、(2.8±0.7)mmol/L、(4.4±1.2)mmol/L、(2.5±0.3)和(6.4±2.1)ng/mL,显著高于早期纤维化患者【分别为(5.2±1.1)mmol/L、(5.7±0.4)mmol/L、(1.9±0.5)mmol/L、(3.1±1.0)mmol/L、(1.4±0.1)和(5.1±1.3)ng/mL,P＜0.05】;49例有高血压、糖尿病或/和高脂血症合并症的NASH患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(6.5±1.9)mmol/L、(6.9±0.8)mmol/L、(2.7±0.8)mmol/L、(4.0±1.1)mmol/L、(2.2±0.3)和(6.3±2.0)ng/mL,显著高于69例无合并症者【分别为(5.5±1.3)mmol/L、(5.7±0.4)mmol/L、(2.2±0.5)mmol/L、(3.5±0.7)mmol/L、(1.7±0.2)和(5.3±1.6)ng/mL,P＜0.05】,而血清HDL-C水平为(1.1±0.2)mmol/L,显著低于无合并症者【(1.3±0.4)mmol/L,P＜0.05】。结论 NASH患者PBMC HIF1a-AS1和血清beclin1水平异常升高,监测其水平可能有助于病情评估。

关键词: 非酒精性脂肪性肝炎, 单个核细胞, 乏氧诱导因子1a-反义RNA 1, Beclin1, 临床意义

Abstract: Objective The aim of this study was to explore the clinical implications of peripheral blood mononuclear cell (PBMC) hypoxia-inducible factor 1a-antisense RNA 1 (HIF1a-AS1)and serum autophagy gene beclin1 in patients with non-alcoholic steatohepatitis (NASH). Methods 118 patients with NASH (early stage in 43 cases, with liver fibrosis in 46 cases and with cirrhosis in 29 cases ) and 118 healthy individuals were enrolled in our hospital between January 2019 and April 2021. The fasting blood glucose (FBG), serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were detected by full-automatic biochemical analyzer. The PBMC HIF1a-AS1 level was detected by real-time fluorescent quantitative PCR. Serum beclin1 level was detected by ELISA. Results The FBG, serum TC, TG, LDL-C, PBMC HIF1a-AS1 and serum beclin1 levels in patients with NASH were (5.9±1.6)mmol/L, (6.2±0.5)mmol/L,(2.4±0.6)mmol/L, (3.7±0.9)mmol/L, (1.9±0.2) and (5.7±1.9)ng/mL, all significantly higher [(4.8±0.7)mmol/L, (5.3±0.3)mmol/L, (1.3±0.3)mmol/L, (2.3±0.6)mmol/L, (1.0±0.1) and (4.1±1.5)ng/mL, respectively, P＜0.05], while serum HDL-C level was (1.2±0.2)mmol/L, significantly lower than [(1.4±0.3)mmol/L, P＜0.05] in healthy persons; the FBG, serum TC, TG, LDL-C, PBMC HIF1a-AS1 and serum beclin1 levels in patients with cirrhotic NASH were(6.8±2.0)mmol/L, (6.8±0.8)mmol/L, (2.8±0.7)mmol/L, (4.4±1.2)mmol/L, (2.5±0.3) and (6.4±2.1)ng/mL, all significantly higher than [(5.2±1.1)mmol/L, (5.7±0.4)mmol/L, (1.9±0.5)mmol/L, (3.1±1.0)mmol/L, (1.4±0.1) and (5.1±1.3)ng/mL, respectively, P＜0.05] in patients with early NASH; the FBG, serum TC, TG, LDL-C, PBMC HIF1a-AS1 and serum beclin1 levels in 49 patients with concomitant hypertension, diabetes and/or hyperlipidemia were (6.5±1.9) mmol/L, (6.9±0.8)mmol/L, (2.7±0.8)mmol/L, (4.0±1.1)mmol/L,(2.2±0.3) and (6.3±2.0)ng/mL, all significantly higher than [(5.5±1.3)mmol/L, (5.7±0.4)mmol/L, (2.2±0.5)mmol/L, (3.5±0.7)mmol/L, (1.7±0.2) and (5.3±1.6)ng/mL, respectively, P＜0.05], while serum HDL-C level was (1.1±0.2)mmol/L, significantly lower than [(1.3±0.4)mmol/L, P＜0.05] in 69 patients without. Conclusion The PBMC HIF1a-AS1 and serum beclin1 levels abnormally increase in patients with NASH, and the surveillance of them might help the disease assessment.

Key words: Non-alcoholic steatohepatitis, Peripheral blood mononuclear cells, Hypoxia-inducible factor 1a-antisense RNA 1, Beclin1, Implications

张羿, 尹刚, 赵艳萍. NASH患者外周血乏氧诱导因子1a-反义RNA 1和自噬基因Beclin1变化及其临床意义^*[J]. 实用肝脏病杂志, 2022, 25(4): 517-520.

Zhang Yi, Yin Gang, Zhao Yanping. Clinical implications of peripheral blood mononuclear cell hypoxia-inducible factor 1a-antisense RNA 1 and serum autophagy gene beclin1 in patients with NASH[J]. Journal of Practical Hepatology, 2022, 25(4): 517-520.

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NASH患者外周血乏氧诱导因子1a-反义RNA 1和自噬基因Beclin1变化及其临床意义^*

Clinical implications of peripheral blood mononuclear cell hypoxia-inducible factor 1a-antisense RNA 1 and serum autophagy gene beclin1 in patients with NASH

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