颅内大动脉粥样硬化型急性脑梗死患者血清Annexin A2、miR⁃9⁃5p表达与颅内动脉粥样斑块负荷、病情严重程度的关系

The relationship between the expression of Annexin A2 and miR⁃9⁃5p in serum and the load of intracranial atherosclerotic plaque and the severity of the disease in patients with acute cerebral infarction of intracranial atherosclerosis

目的分析颅内大动脉粥样硬化型急性脑梗死(ACI)患者血清膜联蛋白A2(Annexin A2)、微小RNA⁃9⁃5p(miR⁃9⁃5p)表达与颅内动脉粥样斑块负荷、病情严重程度的关系。方法选取2019年1月—2022年10月四川省巴中市中心医院神经内科收治的颅内大动脉粥样硬化型ACI患者170例作为研究组,健康体检志愿者173例作为健康对照组。检测实验室指标,酶联免疫吸附法和荧光定量PCR法分别检测血清Annexin A2、miR⁃9⁃5p表达,对颅内大动脉粥样硬化型ACI患者颅内动脉粥样斑块负荷进行测定,根据美国国立卫生研究院卒中量表(NIHSS)评分将ACI患者分为轻度ACI亚组39例、中度ACI亚组56例和重度ACI亚组75例。分析颅内大动脉粥样硬化型ACI患者血清Annexin A2、miR⁃9⁃5p表达及二者与颅内动脉粥样斑块负荷、NIHSS评分的相关性,颅内大动脉粥样硬化型ACI发生的影响因素,血清Annexin A2、miR⁃9⁃5p表达对重度颅内大动脉粥样硬化型ACI发生的预测价值。结果与健康对照组比较,研究组血清三酰甘油(TG)、总胆固醇(TC)、高敏C反应蛋白(hs⁃CRP)、Annexin A2水平均明显升高(t/P=11.636/<0.001、12.198/<0.001、45.099/<0.001、58.651/<0.001),而miR⁃9⁃5p表达明显降低(t/P=34.044/<0.001);轻度ACI亚组、中度ACI亚组、重度ACI亚组血清Annexin A2水平、颅内动脉粥样斑块负荷、NIHSS评分依次升高(F/P=81.628/<0.001、16.766/<0.001、14.000/<0.001),miR⁃9⁃5p表达依次降低(F/P=17.951/<0.001);颅内大动脉粥样硬化型ACI患者血清Annexin A2与miR⁃9⁃5p表达呈负相关(r/P=-0.859/<0.001),血清Annexin A2水平与颅内动脉粥样斑块负荷、NIHSS评分呈正相关(r/P=0.814/<0.001、0.649/<0.001),血清miR⁃9⁃5p表达与颅内动脉粥样斑块负荷、NIHSS评分呈负相关(r/P=-0.737/<0.001、-0.564/<0.001);血清Annexin A2高水平、颅内动脉粥样斑块负荷高是ACI发生的危险因素[OR(95%CI)=1.716(1.201~2.452)、1.924(1.384~2.674)],血清miR⁃9⁃5p高表达是其保护因素[OR(95%CI)=0.835(0.715~0.975)];血清Annexin A2、miR⁃9⁃5p及二者联合预测重度颅内大动脉粥样硬化型ACI发生的曲线下面积(AUC)分别为0.833、0.791、0.925,二者联合预测优于单独预测(Z/P=2.530/0.011、3.364/0.001)。结论颅内大动脉粥样硬化型ACI患者血清Annexin A2水平升高,miR⁃9⁃5p表达降低,与颅内动脉粥样斑块负荷、病情严重程度有关,二者联合对重度ACI有较高的预测价值。

Objective To analyze the relationship between the expression of serum annexin A2,microRNA⁃9⁃5p(miR⁃9⁃5p)in patients with acute cerebral infarction(ACI)of intracranial atherosclerotic type and the burden of intracranial atherosclerotic plaque and the severity of the disease.Methods One hundred and seventy patients with intracranial atherosclerotic ACI admitted to the Department of Neurology,Bazhong Central Hospital,Sichuan Province from January 2019 to October 2022 were selected as the study group,and 173 healthy volunteers were selected as the healthy control group.The laboratory indexes were detected,and the expression of Annexin A2 and miR⁃9⁃5p in serum were detected by ELISA and flu⁃orescent quantitative PCR,respectively.The intracranial atherosclerotic plaque load of patients with intracranial atherosclerotic ACI was measured.According to the NIHSS score,ACI patients were divided into 39 mild ACI subgroups,56 moderate ACI subgroups,and 75 severe ACI subgroups.To analyze the expression of Annexin A2 and miR⁃9⁃5p in serum of patients with intracranial atherosclerotic ACI and their correlation with intracranial atherosclerotic plaque load and NIHSS score,the influen⁃cing factors of the occurrence of intracranial atherosclerotic ACI,and the predictive value of the expression of Annexin A2 and miR⁃9⁃5p in serum on the occurrence of severe intracranial atherosclerotic ACI.Results Compared with the healthy control group,the levels of serum triacylglycerol(TG),total cholesterol(TC),hypersensitive C⁃reactive protein(hs⁃CRP),and annex⁃in A2 in the study group were significantly increased(t/P=11.636/<0.001,12.198/<0.001,45.099/<0.001,58.651/<0.001),and the expression of miR⁃9⁃5p was significantly decreased(t/P=34.044/<0.001);The serum Annexin A2 level,in⁃tracranial atherosclerotic plaque load and NIHSS score in mild ACI subgroup,moderate ACI subgroup and severe ACI sub⁃group increased in turn(F/P=81.628/<0.001,16.766/<0.001,14.000/<0.001),and the expression of miR⁃9⁃5p decreased in turn(F/P=17.951/<0.001);The expression of serum Annexin A2 was negatively correlated with the expression of miR⁃9⁃5p in patients with intracranial atherosclerotic ACI(r/P=-0.859/<0.001),the level of serum Annexin A2 was positively corre⁃lated with the intracranial atherosclerotic plaque load and NIHSS score(r/P=0.814/<0.001,0.649/<0.001),and the expres⁃sion of serum miR⁃9⁃5p was negatively correlated with the intracranial atherosclerotic plaque load and NIHSS score(r/P=-0.737/<0.001,-0.564/<0.001);High level of Annexin A2 in serum,and high load of intracranial atherosclerotic plaque are risk factors for ACI[OR(95%CI)=1.716(1.201-2.452),1.924(1.384-2.674)],high expression of miR⁃9⁃5p is protective factor of ACI[OR(95%CI)=0.835(0.715-0.975)];The area under the curve(AUC)of serum Annexin A2,miR⁃9⁃5p and their com⁃bination in predicting the occurrence of severe intracranial atherosclerotic ACI were 0.833,0.791 and 0.925,respectively,and their combined prediction was better than the single prediction(Z/P=2.530/0.011,3.364/0.001).Conclusion The increase of serum Annexin A2 level and the decrease of miR⁃9⁃5p expression in patients with intracranial atherosclerotic ACI are related to the load of intracranial atherosclerotic plaque and the severity of the disease.The combination of the two has a high predictive value for severe ACI.