缺血性脑卒中患者血清miR-155和PDCD4 mRNA表达水平与颈动脉支架成形术后再狭窄的相关性研究

Correlation between the Expression of miR-155, PDCD4 mRNA and Restenosis after Carotid Artery Stenting in Patients with Cerebral Ischemic Stroke

目的 了解缺血性脑卒中(cerebral ischemic stroke,CIS)患者血清微小RNA-155(micro RNA-155,mi R-155)、程序性细胞死亡因子4(programmed cell death factor 4,PDCD4)信使RNA(messenger RNA,m RNA)表达水平与颈动脉支架成形术(carotid artery stenting,CAS)后再狭窄的相关性。方法 选择2016年2月~2020年7月在凉山彝族自治州第二人民医院确诊的CIS患者120例作为CIS组,同期选取健康体检者125例为对照组。实时荧光定量PCR法测定CIS组术前和术后24 h,对照组体检时血清mi R-155和PDCD4 mRNA表达水平;术后180天对CIS患者进行脑多普勒超声检查和颈动脉彩超检查,观察CIS患者颈动脉狭窄程度、不稳定斑块数量、斑块长度及斑块厚度,测定患者血浆粘度、全血黏度、红细胞比容和纤维蛋白原水平;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清mi R-155和PDCD4 mRNA表达水平对CIS患者行CAS术后再狭窄的诊断价值。结果与对照组相比,CIS组术前血清mi R-155表达水平显著降低(0.31±0.06 vs 1.01±0.20)(q=45.189,P=0.000),CIS组术前(2.23±0.45 vs 1.03±0.20)和术后24 h(1.19±0.29 vs 1.03±0.20)血清PDCD4 mRNA表达水平均显著升高(q=40.422,5.390,均P=0.000),差异均有统计学意义;与CIS组术前相比,CIS组术后24 h血清mi R-155表达水平显著升高(0.97±0.21 vs 0.31±0.06)(q=42.179,P=0.000),血清PDCD4 mRNA表达水平显著降低(1.19±0.23 vs2.23±0.45)(q=34.680,P=0.000),差异均有统计学意义;与未狭窄组相比,再狭窄组颈动脉狭窄程度(21.31±5.33vs 9.11±2.52)、术后24 h血清PDCD4 mRNA表达水平(2.18±0.54 vs 1.06±0.26)、不稳定斑块数量(5.51±1.27 vs2.87±0.71)、斑块长度(7.60±1.90mm vs 3.16±0.79mm)、斑块厚度(4.60±1.15mm vs 2.84±0.71mm)、血浆黏度(15.03±3.85m Pa·s vs 11.01±2.75m Pa·s)、全血粘度(5.84±1.46m Pa·s vs 3.71±0.92m Pa·s)、红细胞比容(58.98%±17.74%vs 46.51%±11.62%)和纤维蛋白原(4.93±1.23g/L vs 3.01±0.75g/L)显著升高,差异均有统计学意义(t=4.277~17.874,均P<0.05),术后24 h血清mi R-155表达水平显著降低(0.36±0.09 vs 1.03±0.25),差异有统计学意义(t=9.074,P=0.000)。ROC曲线结果表明,术后24 h血清mi R-155和PDCD4 mRNA表达水平诊断CAS术后再狭窄的AUC分别为0.778(95%CI为0.692~0.864)和0.838(95%CI为0.749~0.926)。结论 血清mi R-155和PDCD4 mRNA的异常表达与CIS病情及CAS术后再狭窄联系密切,对CAS术后再狭窄具有一定的诊断价值。

Objective To detect the expression levels of microRNA-155(miR-155) and programmed cell death factor 4(PDCD4) messenger RNA(mRNA) in patients with cerebral ischemic stroke(CIS) and analyze the relationship between them and restenosis after carotid artery stenting(CAS) for CIS patients. Methods A total of 120 cases of CIS patients diagnosed in the Second People’s Hospital of Liangshan Yi Autonomous Prefecture from February 2016 to July 2020 were selected as the CIS group, and 125 cases of healthy people were selected as the control group. The expression levels of miR-155 and PDCD4 mRNA in serum of CIS group were measured by real-time quantitative PCR before and 24 hours after operation, and in control group at physical examination. 180 days after operation, the patients with CIS were examined by cerebral Doppler ultrasound and carotid artery color Doppler ultrasound, the degree of carotid stenosis, the number of unstable plaques, the length and thickness of plaques were observed. The plasma viscosity, whole blood viscosity, hematocrit and fibrinogen levels were measured. Receiver operating characteristic(ROC) curve was used to analyze the diagnostic value of serum miR-155 and PDCD4mRNA expression levels in the diagnosis of restenosis after CAS in patients with CIS. Results Compared with those in the control group, the expression level of serum miR-155 of CIS group before operation was significantly lower(0.31±0.06 vs 1.01±0.20)(q=45.189, P=0.000),and the expression level of serum PDCD4 mRNA in CIS group before operation(2.23±0.45vs 1.03±0.20) and 24 hours after operation(1.19±0.29 vs 1.03±0.20) was significantly higher(q=40.422, 5.390, all P=0.000),the differences were statistically significant,respectively. Compared with the CIS group before operation, the expression level of serum miR-155 of CIS group at 24 h after operation was significantly increased(0.97±0.21 vs 0.31±0.06)(q=42.179, P=0.000), and the expression level of serum PDCD4 mRNA was significantly decreased(1.19±0.23 vs 2.23±0.45)(q=34.680, P=0.000), the differences were statistically significant, respectively. And compared with the non stenosis group, the degree of carotid artery stenosis(21.31%±5.33% vs 9.11%±2.52%), the expression level of serum PDCD4 mRNA 24 hours after operation(2.18±0.54 vs 1.06±0.26), the number of unstable plaques(5.51±1.27 vs 2.87±0.71), plaque l e n g t h( 7. 6 0 ± 1. 9 0 m m v s 3. 1 6 ± 0. 7 9 m m), p l a q u e t h i c k n e s s( 4. 6 0 ± 1. 1 5 m m v s 2. 8 4 ± 0. 7 1 m m), p l a s m a viscosity(15.03±3.85mPa·s vs 11.01±2.75mPa·s), whole blood viscosity(5.84±1.46mPa·s vs 3.71±0.92mPa·s),hematocrit(58.98%±17.74% vs 46.51%±11.62%) and fibrinogen(4.93±1.23g/L vs 3.01±0.75g/L) in the restenosis group were significantly increased,the differences were statistically significant(t=4.277~17.874, all P<0.05), and the expression level of serum miR-155 24 hours after operation was significantly decreased(0.36±0.09 vs 1.03±0.25), the difference was statistically significant(t=9.074, P=0.000). ROC curve results showed that the AUC of serum miR-155 and PDCD4 mRNA expression levels 24 hours after operation in the detection of restenosis after CAS was 0.778(95% CI: 0.692~0.864) and 0.838(95% CI:0.749~0.926) respectively. Conclusion The abnormal expression of serum miR-155 and PDCD4 mRNA was closely related to the condition of CIS and restenosis after CAS, which has certain diagnostic value for restenosis after CAS.