血清MMP-9、AFABP和PLGF水平联合检测对妊娠期肝内胆汁淤积症临床评估价值

Evaluating the severity of intrahepatic cholestasis of pregnancy and fetal growth restriction:The combined role of serum MMP-9,AFABP and PLGF levels

目的探讨血清基质金属蛋白酶-9(MMP-9)、脂肪细胞型脂肪酸结合蛋白(AFABP)和胎盘生长因子受体(PLGF)水平检测对妊娠期肝内胆汁淤积症(ICP)临床评估价值。方法将2020年1月-2022年6月南京江北医院收治的70例ICP孕妇列入观察组,选择同期健康产妇40名列入对照组。检测血清MMP-9、AFABP、PLGF、丙氨酸氨基转移酶(ALT)、白蛋白(Alb)、总胆红素(TBil)、总胆汁酸(TBA)、甘胆酸(CG)水平,采用Ribalta评分法评价瘙痒症状的严重程度。根据TBA和TBil水平分为轻度组(n=31)、中度组(n=24)和重度组(n=15),根据是否出现胎儿生长受限(FGR)分为未合并FGR组(n=57)和合并FGR组(n=13)。比较观察组和对照组的ALT、Alb、CG、MMP-9、AFABP和PLGF水平,并比较观察组中不同病情严重程度和是否合并FGR亚组的MMP-9、AFABP和PLGF水平,Pearson分析MMP-9、AFABP和PLGF水平与血清ALT、Alb、CG水平和Ribalta评分的相关性,ROC分析单独和联合检测的评估效能。结果观察组的ALT、CG、MMP-9和AFABP分别为(150.43±13.65)U/L、(17.52±4.28)mg/L、(786.38±62.85)ng/mL、(35.80±6.47)μg/L,高于对照组的(36.74±5.28)U/L、(1.86±0.37)mg/L、(542.71±48.93)ng/mL、(21.38±4.65)μg/L,观察组的PLGF为(1.47±0.39)ng/mL,低于对照组的(2.75±0.68)ng/mL,差异有统计学意义(t=12.056、19.825、10.734、9.428、8.529,均P<0.05)。观察组中,重度亚组的MMP-9和AFABP分别为(852.86±70.25)ng/mL和(41.09±8.13)μg/L,高于中度和轻度亚组的(773.90±61.49)ng/mL和(36.47±6.70)μg/L、(680.47±53.42)ng/mL和(30.82±5.34)μg/L;重度亚组的PLGF为(1.15±0.29)ng/mL,低于中度和轻度亚组的(1.43±0.38)和(1.76±0.45)ng/mL,差异有统计学意义(F=24.825、38.764、28.492,均P<0.05)。观察组中合并FGR亚组的MMP-9和AFABP分别为(863.78±72.54)ng/mL和(41.37±8.26)μg/L,高于未合并FGR亚组的(735.64±58.91)ng/mL和(33.61±6.25)μg/L,合并FGR亚组的PLGF为(1.13±0.28)ng/mL,低于未合并FGR亚组的(1.61±0.42)ng/mL,差异有统计学意义(t=8.736、9.872、9.034,均P<0.05)。Pearson分析显示,观察组的MMP-9和AFABP水平与ALT、CG和Ribalta评分呈正相关;PLGF水平与ALT、CG和Ribalta评分呈负相关(P<0.01)。ROC分析显示,MMP-9、AFABP和PLGF水平单独及联合检测评估ICP的AUC分别为0.684、0.753、0.709和0.921,联合检测的敏感度和特异度均高于任一单项检测(P<0.01)。结论血清MMP-9、AFABP和PLGF水平联合检测对ICP患者的病情程度和发生FGR的临床评估价值较高。

Objective To investigate the clinical significance of serum matrix metalloproteinase-9(MMP-9),adipocytic fatty acid-binding protein(AFABP)and placental growth factor receptor(PLGF)levels in assessing the severity of intrahepatic cholestasis of pregnancy(ICP).Methods From January 2020 to June 2022,70 pregnant women diagnosed with ICP were selected as the observation group,while 40 healthy pregnant womenfrom the same period as the control group.Serum levels of MMP-9,AFABP,PLGF,alanine aminotransferase(ALT),albumin(Alb),total bilirubin(TBil),total bile acid(TBA)and glycholic acid(CG)were detected.The severity of pruritis was evaluated using the Ribalta score.According to TBA and TBil levels,the participants were divided into mild(n=31),moderate(n=24)and severe(n=15)group.Based on the presence or absence of FGR,they were further classified into non-combined FGR(n=57)and combined FGR(n=13)subgroups.We compared levels of ALT,Alb,CG,MMP-9,AFABP and PLGF between the observation and control groups,and among the subgroups with different disease severities and FGR status within the observation.Pearson correlation was used to analyze the relationship between levels of MMP-9,AFABP,PLGF,ALT,Alb,CG and the Ribalta score.The effectiveness of single and combined detection was evaluated using ROC analysis.Results In the observation group,the levels of ALT,CG,MMP-9 and AFABP were 150.43±13.65 U/L,17.52±4.28 mg/L,786.38±62.85 ng/mL,35.80±6.47μg/L,respectively.The PLGF level in the observation group was 1.47±0.39 ng/mL,siginificantly lower than the control group`s levels(36.74±5.28 U/L,1.86±0.37 mg/L,542.71±48.93 ng/mL,21.38±4.65μg/L)(t=12.056,19.825,10.734,9.428,8.529,all P<0.05).Within the observation groups,the moderate to severe subgroup had higher MMP-9 and AFABP levels(852.86±70.25 ng/mL and 41.09±8.13μg/L,respectively)than the moderate and mild subgroups(773.90±61.49 ng/mL,36.47±6.70μg/L,680.47±53.42 ng/mL,30.82±5.34μg/L,respectively).The severe subgroup had a lower PLGF level(1.15±0.29 ng/mL)compared to the moderate and mild subgroups(1.43±0.38 ng/mL and 1.76±0.45 ng/mL,respectively),with these differences being statistically significant(F=24.825,38.764,28.492,all P<0.05).Moreover,In the observation group,the FGR subgroup had higher MMP-9 and AFABP levels(863.78±72.54 ng/mL and 41.37±8.26μg/L,respectively),and a lower PLGF level(1.13±0.28 ng/mL)compared to the non-FGR subgroup(735.64±58.91 ng/mL,33.61±6.25μg/L and 1.61±0.42 ng/mL,respectively),with these differences also being,statistically significant(t=8.736,9.872,9.034,all P<0.05).Pearson analysis showed that the levels of MMP-9 and AFABP were positively correlated with ALT,CG and Ribalta scores in the observation group,while,PLGF levels had a negatively correlation(P<0.01).ROC analysis revealed that the AUC for MMP-9,AFABP and PLGF,both individually and combined were 0.684,0.753,0.709 and 0.921,respectively.The sensitivity and specificity of combined detection surpassed those of any single detection(P<0.01).Conclusion Simultaneously assessing serum levels of MMP-9,AFABP and PLGF offer significant clinical utility in determining the severity of ICP and the incidence of FGR.