心力衰竭患者血清中内质网应激标志物GRP78的水平变化及其在评估近期预后中的价值

Level changes in serum endoplasmic reticulum stress marker GRP78 in patients with heart failure and its value in evaluating short-term prognosis

目的:探讨心力衰竭患者血清中内质网应激标志物葡萄糖调节蛋白-78(GRP78)的水平变化及其在评估近期预后中的价值。方法:本研究采用ELISA法测定80例心力衰竭患者(HF)血清中的GRP78水平,并收集40例健康体检者作为对照,对心力衰竭患者随访1年,记录预后情况。应用SPSS 23.0软件处理临床资料。结果:HF组较对照组血清中的GRP78(ng/mL)水平高(414.0±89.8 vs. 377.1±64.8,P<0.05);GRP78水平在不同的心功能临床分级间比较差异无统计学意义(心衰Ⅱ级vs.心衰Ⅲ级:422.7±85.4 vs. 418.6±68.8,P=0.522;心衰Ⅱ级vs.心衰Ⅳ级:422.7±85.4 vs. 442.1±151.3,P=0.285;心衰Ⅲ级vs.心衰Ⅳ级:418.6±68.8 vs. 442.1±151.3,P=0.223);不良事件组的血清GRP78水平明显高于非不良事件组(436.7±96.4 vs. 389.8±80.1,P<0.001);经独立危险因素非条件Logistic二元回归模型分析,GRP78、NT-ProBNP 2个变量均对HF预后有独立预测意义,OR值分别为1.017、1.001;以GRP78取430 ng/mL为cutoff值评估不良预后,其敏感度为56.5%、特异度为94.1%、阳性预测值为92.9%、阴性预测值为61.5%、准确率为72.5%;若联合NT-ProBNP评估预后,结果更优,ROC曲线下面积为0.883。结论:内质网应激在心力衰竭的发生发展过程中起着重要的作用;GRP78对HF患者的诊断有一定的提示性作用,可以作为独立评估HF患者预后的预测因子,若结合生物标记物NT-ProBNP,则评估效能更佳。

Objective: To investigate the level changes of endoplasmic reticulum stress marker GRP78 in serum and the value of assessing the short-term prognosis in patients with heart failure(HF). Method: In this study, the GRP78 in serum of 80 patients with HF was measured by ELISA as experimental groups, while 40 healthy subjects were collected as control group. The patients were followed up for one year and their prognosis was recorded. Clinical data were processed with SPSS 23.0 software. Result: GRP78(ng/mL) level in experimental group was higher than control group(414.0±89.8 vs. 377.1±64.8, P<0.05). There were no significant differences among groups according to NYHA heart function classification(levels Ⅱ vs. Ⅲ: 422.7±85.4 vs. 418.6±68.8, P=0.522;levels Ⅱ vs. Ⅳ: 422.7±85.4 vs. 442.1±151.3, P=0.285;levels Ⅲ vs. Ⅳ: 418.6±68.8 vs. 442.1±151.3, P=0.223);GRP78 level in the adverse event group was significantly higher than that in the non-adverse event group(436.7±96.4 vs. 389.8±80.1, P<0.001). Through the analysis of independent risk factors by nonconditional logistic binary regression model, both of GRP78 and NT-proBNP were independent predictors for HF prognosis, the OR values were 1.017 and 1.001, respectively. GRP78 was used as cutoff value to evaluate poor prognosis, with sensitivity of 56.5%, specificity of 94.1%, positive predictive value of 92.9%, negative predictive value of 61.5%, and accuracy of 72.5%. However, the result was better when combining GRP78 with NT-proBNP to evaluate the prognosis, with the area under the ROC curve 0.883. Conclusion: Endoplasmic reticulum stress played an important role in the development of heart failure. GRP78 had a certain suggestive effect on the diagnosis of HF patients, which can be used as a predictive factor for independent assessment of the prognosis of HF patients. The evaluation efficiency was better, if combined with the biomarker NT-proBNP.