急性缺血性脑卒中患者外周血自噬及凋亡相关基因表达水平及临床意义

The Expression Level and Clinical Significance of Autophagy and Apoptosis-related Genes in Peripheral Blood of Patients with Acute Ischemic Stroke

目的观察急性缺血性脑卒中(AIS)患者外周血自噬及凋亡相关基因的表达水平及临床意义。方法收集168例AIS患者为AIS组,选择同期健康体检者60例为对照组。评估AIS组预后,将AIS组分为预后良好亚组(116例)和预后不良亚组(52例)。q RT-PCR法检测各组外周血单个核细胞(PBMCs)中自噬(Beclin1、LC3Ⅱ)及凋亡(Bax、Bcl-2)相关基因的mRNA水平;酶联免疫吸附法检测炎性因子白细胞介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)和氧化应激因子丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果与对照组比较,AIS组PBMC中Beclin1、LC3Ⅱ、Bax mRNA水平显著升高(均P<0.05);IL-1β、TNF-α及MDA水平显著升高(均P<0.05),Bcl-2 mRNA和SOD水平显著降低(均P<0.05)。与预后良好亚组比较,预后不良亚组Beclin1 mRNA、LC3ⅡmRNA、Bax mRNA及IL-1β、TNF-α、MDA水平升高(均P<0.05);Bcl-2 mRNA和SOD水平降低(均P<0.05)。相关性分析提示AIS组Beclin1和LC3Ⅱm RNA分别与Bax mRNA和m RS评分呈正相关(均P<0.05),与Bcl-2 mRNA和SOD呈负相关(均P<0.05)。ROC曲线表明,Beclin1 mRNA和LC3Ⅱm RNA对患者预后评估的AUC分别为0.870(95%CI:0.811~0.929)和0.837(95%CI:0.764~0.910),敏感度分别为81.67%和87.72%,特异度分别为77.03%和74.19%。结论AIS患者外周血Beclin1、LC3Ⅱ、Bax mRNA和IL-1β、TNF-α、MDA水平显著升高,Bcl-2 mRNA和SOD水平显著降低,与AIS预后相关;对评估AIS预后具有临床应用价值。

Aim To observe the expression level and clinical significance of autophagy and apoptosisrelated genes in peripheral blood of patients with acute ischemic stroke(AIS).Methods 168 patients with AIS as an AIS group and 60 persons with healthy physical examination during the same period were selected as a control group.AIS group was divided into a good prognosis group(116 cases)and a poor prognosis group(52 cases)by assessing their prognosis.mRNA levels of autophagy(Beclin1,LC3)and apoptosis(Bax,Bcl-2)related genes in peripheral blood mononuclear cells(PBMC)in each group were detected by QRT-PCR.The related inflammatory cytokines IL-1β,TNF-α and oxidative stress malondialdehyde(MDA),and superoxide dismutase(SOD)level were measured by enzyme-linked immunosorbent assay.Results Compared with the control group,the levels of Beclin-1,LC3,and Bax mRNA in the peripheral blood PBMC of the AIS group were significantly increased(P<0.05),and IL-1β,TNF-α and MDA levels were significantly increased(all P<0.05);Bcl-2 mRNA and SOD levels were significantly reduced(both P<0.05).Compared with the good prognosis subgroup,the levels of Beclin-1 mRNA,LC3 m RNA and Bax mRNA,and IL-1β,TNF-αand MDA levels in the poor prognosis group were significantly increased(all P<0.05);the Bcl-2 mRNA and SOD level was significantly reduced(both P<0.05).Correlation analysis showed that Beclin1 and LC3 m RNA in the AIS group were positively correlated with Bax mRNA and m RS scores(P<0.05),and negatively correlated with Bcl-2 mRNA and SOD(P<0.05).The ROC curve analysis showed that the area under the curve(AUC)of Beclin1 mRNA and LC3 m RNA for prognostic evaluation of patients were 0.870(95%CI:0.811-0.929)and 0.837(95%CI:0.764-0.910),respectively;their sensitivity was 81.67% and 87.72%,respectively;the specificity was 77.03% and 74.19%,respectively.Conclusion The Beclin1,LC3,Bax m RNA,IL-1β,TNF-α and MDA levels in the peripheral blood of AIS patients are significantly increased and Bcl-2 mRNA and SOD levels are significantly reduced,which are related to the prognosis.It has significantly clinical application value for the prognosis evaluation of AIS.