高原红细胞增多症患者外周血miRNA表达特征及其与肝功能损害的相关性

摘要/Abstract

摘要： 目的探讨高原红细胞增多症(HAPC)患者外周血miRNA表达差异,分析外周血miRNA水平与HAPC肝功能损害的相关性。方法选取从平原地区移居至海拔4 300米以上高原地区的100例HAPC患者并设为HAPC组;另选取同海拔地区健康人群100名设为对照组。收集两组临床实验室资料,采用16S rRNA高通量测序技术对每组各10例研究对象进行测序,筛选有差异的miRNA。对所有研究对象采用实时荧光定量PCR技术检测差异miRNA表达情况。另根据HAPC组患者肝功能受损情况(ALT≥2倍正常值上限)分为肝功能受损组和肝功能未受损组;logistic回归分析探讨HAPC组肝功能受损的独立相关因素;Pearson相关性分析差异miRNA与肝功能的相关性。结果 HAPC组SpO2低于对照组,RBC、Hb水平高于对照组,差异具有统计学意义(P<0.05);16S rRNA高通量测序结果显示,HAPC组与对照组共有322个差异表达miRNA,其中115个显著差异表达,上调75个,下调40个。选取其中表达量丰度高、稳定且差异倍数较大的前10个miRNA进行验证,PCR验证结果显示,HAPC组miR-122-5p、miR-423-5p、miR-23a、miR-451a、miR-223、miR-486-3p、miR-183-5p、miR-1291相对表达量高于对照组,miR-200c-3p、miR-150-5p相对表达量低于对照组(P<0.05);HAPC组患者的亚组分析显示,肝功能受损组miR-23a、miR-451a、miR-223相对表达量明显高于肝功能未受损组,差异具有统计学意义(P<0.05);logistic回归分析显示,miR-451a(OR=3.288)、miR-223(OR=1.232)和Hb水平(OR=1.139)与HAPC患者肝功能受损独立相关(P<0.05);Pearson相关性分析显示,miR-451a、miR-223相对表达量与HAPC患者ALT水平呈正相关(r=0.743、0.683,P<0.05)。结论高原红细胞增多症患者与同海拔地区健康人群相比,其miRNA表达存在显著差异,miR-451a、miR-223高表达可能与HAPC患者肝功能受损有关。

关键词: 高原红细胞增多症, 外周血miRNA, 肝功能受损, 相关性

Abstract: Objective To explore the differences in miRNA expression in the peripheral blood of patients with High Altitude Polycythemia (HAPC) and to analyze the correlation between peripheral blood miRNA levels and liver function damage in HAPC. Methods A total of 100 HAPC patients who moved from plain areas to areas above 4 300 meters in altitude were collected and set as the HAPC group; another 100 healthy individuals from the same altitude area were selected as the control group. Clinical laboratory data of both groups were collected, and 16S rRNA high-throughput sequencing technology was used to sequence 10 subjects from each group to screen for differentially expressed miRNAs. Real-time fluorescence quantitative PCR technology was used to detect the expression of differential miRNAs in all subjects. Additionally, based on the liver function damage status (ALT ≥ 2 times the upper limit of the normal value) of the HAPC group patients, they were divided into liver function damage group and non-damage group; logistic regression analysis was performed to analyze the independent correlative factors of liver function impairment in HAPC group. Pearson correlation analysis was used to analyze the correlation between differential miRNAs and liver function. Results The SpO₂ of the HAPC group was lower than that of the control group, and the levels of RBC and Hb were higher than those of the control group, with statistically significant differences (P<0.05); 16S rRNA high-throughput sequencing results showed that there were 322 differentially expressed miRNAs between the HAPC group and the control group, among which 115 were significantly differentially expressed, with 75 up-regulated and 40 down-regulated. The top 10 miRNAs with high expression, stability, and large fold changes were selected for validation, and PCR validation results showed that the relative expression levels of miR-122-5p, miR-423-5p, miR-23a, miR-451a, miR-223, miR-486-3p, miR-183-5p, and miR-1291 in the HAPC group were higher than those in the control group, while the relative expression levels of miR-200c-3p and miR-150-5p were lower than those in the control group (P<0.05); subgroup analysis of the HAPC group patients showed that the relative expression levels of miR-23a, miR-451a, and miR-223 in the liver function damage group were significantly higher than those in the non-damage group, with statistically significant differences (P<0.05); Logistic regression analysis showed that miR-451a (OR=3.288), miR-223 (OR=1.232), and Hb levels (OR=1.139) were independently associated with liver function damage in HAPC patients (P<0.05); Pearson correlation analysis showed that the relative expression levels of miR-451a and miR-223 were positively correlated with the ALT levels in HAPC patients (r=0.743, 0.683, P<0.05). Conclusion Compared with healthy individuals at the same altitude, HAPC patients have significant differences in miRNA expression, and the high expression of miR-451a and miR-223 may be related to liver function damage in HAPC patients.

Key words: High altitude polycythemia, Peripheral blood miRNA, Liver function damage, Correlation

白洁, 黄河, 浩光东, 白云. 高原红细胞增多症患者外周血miRNA表达特征及其与肝功能损害的相关性[J]. 肝脏, 2026, 31(1): 96-101.

BAI Jie, HUANG He, HAO Guang-dong, BAI Yun. The expression characteristics of miRNA in peripheral blood of patients with high altitude polycythemia and its correlation with liver function damage[J]. Chinese Hepatolgy, 2026, 31(1): 96-101.

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