病毒性脑膜炎患者PCT与VEGF和S100β蛋白及MMP水平及MMP-2基因多态性分析

Detection of PCT,VEGF,S100βprotein,MMP levels and metalloproteinase-2 gene polymorphism in patients with viral meningitis

目的探究分析病毒性脑膜炎患者的降钙素原(Procalcitonin,PCT)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)、中枢神经特异性蛋白β(S100β)、金属基质蛋白酶(Matrix metalloproteinase,MMP)水平及MMP-2基因多态性。方法选择2016年1月-2018年12月于天津市第一中心医院就诊的病毒性脑膜炎患者70例作为研究组,另选取同期于医院体检的健康者30名作为对照组,抽取两组的空腹静脉血4 ml,行腰穿术取脑脊液2 ml,检测患者PCT,及VEGF、S100β、MMP-2水平。提取基因组行PCR扩增,将PCR扩增产物经Hinf I内切酶消化后行2%琼脂糖凝胶电泳,根据电泳结果记录各基因型。结果研究组患者的血清PCT、VEGF、S100β和MMP-2分别为(5.61±0.96)ng/ml、(41.42±3.25)ng/L、(1.36±0.28)ng/ml和(913.47±43.62)ng/ml均高于对照组(P<0.001)。研究组患者脑脊液PCT、VEGF、S100β和MMP-2分别为(0.67±0.12)ng/ml、(60.32±5.94)ng/L、(2.14±0.43)ng/ml、(98.24±9.32)ng/ml均高于对照组(P<0.001)。两组的各基因型分布经χ^2检验,均符合Hardy-Weinberg平衡。研究组-735 C/T位点的CC基因型频率64.29%、CT基因型频率32.86%与对照组比较,差异有统计学意义(P<0.05)。研究组的-735C/T位点C等位基因频率78.57%、T等位基因频率21.43%与对照组比较,差异有统计学意义(P<0.05)。结论病毒性脑膜炎患者的PCT、VEGF、S100β、MMP-2水平均呈升高趋势,可为病毒性脑膜炎诊断提供参考,MMP-2基因启动子区-735 C/T位点多态性可能与病情易感性有关,C基因可能为易感基因,T基因为保护基因。

OBJECTIVE To explore the levels of procalcitonin(PCT),vascular endothelial growth factor(VEGF),central nervous system-specific protein(S100β),and metalloproteinase(MMP)and metalloproteinase-2(MMP-2)gene polymorphism in patients with viral meningitis.METHODS A total of 70 patients with viral meningitis in the Tianjin First Central Hospital from Jan.2016 to Dec.2018 were selected as the study group,and 30 healthy subjects from the same period in the hospital were selected as the control group.4 ml of fasting venous blood and 2 ml of cerebrospinal fluid by lumbar puncture were taken,and PCT,VEGF,S100β,MMP-2 levels were detected.The extracted genome was subjected to PCR amplification,and the PCR amplification product was digested with Hinf I endonuclease,and subjected to 2%agarose gel electrophoresis,and each genotype was recorded according to the electrophoresis result.RESULTS The serum levels of PCT,VEGF,S100β,and MMP-2 in the study group were(5.61±0.96)ng/ml,(41.42±3.25)ng/L,(1.36±0.28)ng/ml and(913.47±43.62)ng/ml,respectively,significantly higher than in the control group(P<0.001).The PCT,VEGF,S100β,and MMP-2 levels of cerebrospinal fluid in the study group were(0.67±0.12)ng/ml,(60.32±5.94)ng/L,(2.14±0.43)ng/ml and(98.24±9.32)ng/ml,respectively,significantly higher than those in the control group(P<0.001).The genotype distribution of the two groups was tested by χ^2 test,which was consistent with Hardy-Weinberg equilibrium.The CC genotype frequency of the observation group and the CT genotype frequency at-735 C/T locus was 64.29%and 32.86%,respectively,significantly different from those in the control group(P<0.05).The C-allele frequency and the T allele frequency at the-735 C/T locus in the observation group was 78.57%and 21.43%,respectivley,significantly different from those in the control group(P<0.05).CONCUSION The levels of PCT,VEGF,S100βand MMP-2 in patients with viral meningitis are increasing,which may provide a reference for the diagnosis of viral meningitis.The polymorphism of-735 C/T locus in the promoter region of MMP-2 gene may be related to the susceptibility of the disease,the C gene may be a susceptible gene,and the T gene is a protective gene.