Expression and clinical significance of glucose regulatory protein 78 and miR-181-5p in peripheral blood of patients with acute pancreatitis
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摘要:目的 探讨急性胰腺炎（AP）患者血清葡萄糖调节蛋白78（GRP78）、miR-181-5p的表达水平及其临床意义。方法 选取141例AP患者作为研究对象，依据AP严重程度分为轻症组86例和重症组55例。另选取同期体检的健康人员100例纳入对照组。采用实时荧光定量PCR法检测受试者血清miR-181-5p、GRP78 mRNA表达水平。采用Pearson相关分析法分析血清miR-181-5p、GRP78 mRNA表达水平的相关性。采用受试者工作特征（ROC）曲线分析血清miR-181-5p、GRP78 mRNA表达水平对重症AP的预测价值。结果 对照组、轻症组、重症组的血清miR-181-5p表达水平依次升高，GRP78 mRNA表达水平依次降低，差异有统计学意义（P < 0.05）。miR-181-5p与GRP78 mRNA表达水平呈负相关（r=-0.665，P < 0.05）。miR-181-5p表达水平偏高、GRP78 mRNA表达水平偏低是重症AP的危险因素（P < 0.05）。ROC曲线显示，血清miR-181-5p预测重症AP的曲线下面积（AUC）为0.836，血清GRP78 mRNA预测重症AP的AUC为0.741，二者联合预测重症AP的AUC为0.861。结论 AP患者血清miR-181-5p表达水平升高，GRP78 mRNA表达水平降低。miR-181-5p、GRP78与AP严重程度有关，对重症AP具有一定预测价值，可作为重症AP的潜在预测标志物。
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关键词:
- 急性胰腺炎 /
- 葡萄糖调节蛋白78 /
- 热休克蛋白家族A成员5 /
- miR-181-5p /
- 预测效能
Abstract:Objective To investigate the expression and clinical significance of peripheral blood glucose regulatory protein 78 (GRP78) and miR-181-5p in patients with acute pancreatitis (AP).Methods A total of 141 AP patients were selected as research objects. According to the severity of AP, they were divided into mild group (86 cases) and severe group (55 cases). A total of 100 healthy people who underwent physical examinations in our hospital during the same period were selected as control group. Real-time fluorescent quantitative PCR method was used to detect the expression levels of serum miR-181-5p and GRP78 mRNA in subjects. Pearson method was used to analyze the correlation between serum miR-181-5p and GRP78 mRNA expression level. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum miR-181-5p and GRP78 mRNA expression levels for severe AP.Results The expression levels of serum miR-181-5p in the control group, the mild group, and the severe group increased sequentially, and their expression levels of GRP78 mRNA decreased (P < 0.05). The expression level of miR-181-5p was negatively correlated with GRP78 mRNA (r=-0.665, P < 0.05). Higher level of miR-181-5p and lower level of GRP78 mRNA were risk factors affecting severe AP (P < 0.05). ROC curve showed that the area under the curve (AUC) was 0.836 predicting severe AP by serum miR-181-5p, was 0.741 by serum GRP78 mRNA, and was 0.861 by combined detection.Conclusion The miR-181-5p expression level in serum increases and the GRP78 mRNA expression level decreases in AP patients, they are both related to the severity of AP. They have a certain predictive value for severe AP and may be used as potential predictive markers. -
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表 1 qRT-PCR引物序列
基因 正向引物5′-3′ 反向引物5′-3′ miR-181-5p AACATTCATTGCTGTCGGTGG GAACATGTCTGCGTATCTC U6 TGCGGGTGCTCGCTTCGCAGC CCAGTGCAGGGTCCGAGGT GRP78 mRNA CCAAGAGAGGGTTCTTGAATCTCG ATGGGCCAGCCTGGATATACAACA GAPDH CTGACTTCAACAGCGACACC TGTGGTAGCCAAATTCGTTGT 
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表 2 3组受试者一般资料比较(x±s)[n(%)]
指标 对照组(n=100) 轻症组(n=86) 重症组(n=55) 年龄/岁 46.18±5.22 46.15±5.83 45.69±5.92 性别 男 47(47.00) 40(46.51) 25(45.45) 女 53(53.00) 46(53.49) 30(54.55) 初诊时WBC/(×109/L) 5.48±1.26 11.56±2.61* 14.72±3.93*# Hb/(g/L) 135.42±16.73 91.14±18.43* 85.36±10.15*# PLT/(×109/L) 132.18±29.37 72.18±18.84* 48.76±12.85*# TC/(mmol/L) 4.75±0.72 4.58±0.69 4.48±0.65 TG/(mmol/L) 2.58±0.79 2.67±0.83 2.74±0.87 LDL-C/(mmol/L) 2.74±0.42 2.72±0.44 2.69±0.49 HDL-C/(mmol/L) 1.58±0.32 1.63±0.35 1.65±0.33 WBC: 白细胞; Hb: 血红蛋白; PLT: 血小板; TC: 总胆固醇; TG: 甘油三酯; LDL-C: 低密度脂蛋白胆固醇;
HDL-C: 高密度脂蛋白胆固醇。与对照组比较, *P < 0.05; 与轻症组比较, #P < 0.05。
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表 3 3组血清miR-181-5p、GRP78 mRNA表达水平比较(x±s)
组别 n miR-181-5p GRP78 mRNA 对照组 100 1.05±0.19 1.01±0.21 轻症组 86 1.68±0.43* 0.75±0.17* 重症组 55 2.74±0.68*# 0.38±0.11*# 与对照组比较, *P < 0.05; 与轻症组比较, #P < 0.05。
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表 4 重症AP影响因素的二元Logistic回归分析
变量 β SE wald P OR 95%CI WBC 0.232 0.209 1.231 0.267 1.261 0.837~1.899 Hb 0.318 0.228 1.942 0.163 1.374 0.879~2.148 PLT 0.267 0.215 1.542 0.214 1.306 0.857~1.990 miR-181-5p 0.695 0.147 22.330 < 0.001 2.003 1.502~2.672 GRP78 mRNA 0.854 0.216 15.631 < 0.001 2.349 1.538~3.587 WBC: 白细胞; Hb: 血红蛋白; PLT: 血小板; GRP78: 葡萄糖调节蛋白78。
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