血管生成素1与急性缺血性卒中患者侧支循环的关系

Relationship between angiogenin-1 and collateral circulation in patients with acute ischemic stroke

目的探讨血管生成素1(Ang-1)与急性缺血性卒中患者侧支循环的关系。方法回顾性连续纳入2015年10月至2017年12月在贵州医科大学附属医院及附属白云医院神经内外科住院诊断为急性缺血性卒中(发病2 d内入院),并在入院2 d内行DSA提示大脑前循环梗死的患者89例,根据美国介入和治疗神经放射学学会/介入放射学学会(ASITN/SIR)侧支循环评估系统对患者DSA影像的侧支循环进行分级并分组,0~1级侧支循环差的患者入组A组(30例),2级侧支循环中等患者入组B组(30例),3~4级侧支循环好的患者入组C组(29例);另连续收集同期行DSA提示颅内外血管未见明显异常的患者31例作为对照组。收集研究对象的临床资料,包括姓名、年龄、性别、高血压史、糖尿病史、吸烟史、饮酒史,并采集研究对象入院2 d内,第7、14、21天晨起空腹血,采用酶联免疫吸附测定(ELISA)法检测血清中及Western Blot测定外周血单核细胞(PBMC)中Ang-1表达水平并进行各组间的比较。结果 4组患者年龄、性别、高血压史、糖尿病史、吸烟史、饮酒史差异均无统计学意义(均P>0.05)。4组患者不同时间血清总体Ang-1水平比较,差异有统计学意义(总体交互效应F=277.597,P<0.01);对照组入院后不同时间点血清Ang-1表达水平差异无统计学意义(F=1.452,P>0.05),而A、B、C组患者血清Ang-1水平在入院2 d内表达水平最高,之后逐渐下降(F值分别为23.896、31.805、18.039,均P<0.01)。同一时间点各组间患者血清Ang-1水平差异均有统计学意义(均P<0.05),A、B、C组血清Ang-1表达水平均较对照组增高(均P<0.05),且侧支循环越好,Ang-1的表达水平越高(均P<0.05)。入院2 d内对照组和A、B、C组患者PBMC Ang-1目的蛋白/内参的积分光密度值的比值(AR)分别为0.07±0.01、0.31±0.02、0.62±0.05、0.81±0.05,组间AR值差异有统计学意义(F=221.50,P<0.01);A、B、C组患者PBMC中Ang-1表达水平AR值均明显高于对照组,侧支循环越好,AR值越高,差异均有统计学意义(均P<0.01)。结论急性缺血性卒中患者Ang-1表达水平升高。侧支循环较好的患者在急性缺血性卒中发展过程中Ang-1表达水平更高,Ang-1可能与急性缺血性卒中患者侧支循环的形成有关。

Objective To investigate the relationship between Angiogenin-1（ Ang-1） and collateral circulation in patients with acute ischemic stroke. Methods From October 2015 to December 2017,89 consecutive patients diagnosed as acute ischemic stroke（ hospitalized within 2 d of onset） and DSA revealing anterior cerebral circulation infarction within 2 d after admission and admitted to the Affiliated Hospital of Guizhou Medical University and the Department of Neurology,the Affiliated Baiyun Hospital were enrolled. The collateral circulation of the DSA images of patients were graded and grouped according to American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology（ ASITN/SIR） collateral circulation assessment system. The patients with poor collateral circulation（ grade0-1） were divided into group A（ n = 30）,those with moderate collateral circulation（ grade 2） were divided into group B（ n = 30）,and those with good collateral circulation（ grade 3-4） were divided into group C（ n = 29）. Another 31 consecutive patients with DSA revealing no abnormalities in the intracranial and extracranial vessels at the same time period were collected and served as a control group. The clinical data of the study subjects were collected,including name,age,gender,histories of hypertension,diabetes,smoking and drinking. The morning fasting blood of the subjects were sampled within 2 days of admission,on day 7,day 14,and day 21. Enzyme-linked immunosorbent assay（ ELISA） was used to detect the Ang-1 expression levels in serum and Western Blot was used to detect the Ang-1 expression levels in peripheral blood mononuclear cells（ PBMC）. Statistical methods were used to compare the difference of the general clinical data and the Ang-1 expression level in each group. Results There were no significant differences in age,gender,histories of hypertension,diabetes,smoking and drinking among the four groups（ all P〉0. 05）. There were significant differences in serum total Ang-1 levels at different times among the 4 groups（ overall interaction effect F = 277. 597,P〈0. 01）. There were no significant differences in the expression levels of Ang-1 in the control group after admission at different time points（ F = 1. 452,P〉0. 05）. However,Ang-1 levels were the highest within 2 days after admission,and then gradually decreased in the patients of group A,B and C（ F values were 23. 896,31. 805,and 18. 039,respectively,all P〈0. 01）. At the same time point,the serum Ang-1 level of each group was statistically significant（ all P〈0. 05）. The serum Ang-1 expression levels of group A,B and C were higher than those of the control group（ all P〈0. 05）,and the better the collateral circulation,the higher the expression level of Ang-1（ all P〈0. 05）. The absorbance ratio（ AR）values of the Ang-1 target protein/internal reference in PBMC in the control group and group A,B and C within 2 days of admission were 0. 07 ± 0. 01,0. 31 ± 0. 02,0. 62 ± 0. 05,and 0. 81 ± 0. 05,respectively.The difference of AR values among the groups were statistically significant（ F = 221. 50,P〈0. 01）. The AR values of the Ang-1 expression levels in PBMC in group A,B and C were significantly higher than the control group. The better the collateral circulation,the higher the AR value,and the difference was statistically significant（ all P〈0. 01）. Conclusions The Ang-1 expression level increased in patients with acute ischemic stroke. The Ang-1 expression levels were higher in patients with better collateral circulation in the development of acute ischemic stroke. It was speculated that Ang-1 might be associated with the formation of collateral circulation in patients with acute ischemic stroke.