急性肝衰竭小鼠血清与组织中PTX3、HBP、PCT及IL-6、IL-1β、TNF-α的变化及诊断价值

Diagnostic Value of Serum and Tissue PTX3, HBP, PCT and IL-6, IL-1β, TNF-α Levels in Acute Liver Failure Mice

目的探讨急性肝衰竭(acute liver failure,ALF)小鼠血清与组织中正五聚蛋白3(pentraxin 3,PTX3)、肝素结合蛋白(heparin-binding protein,HBP)、降钙素原(procalcitonin,PCT)及白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平的变化及诊断价值。方法将32只雄性小鼠随机分为正常组和模型组,每组16只。用D-氨基半乳糖联合脂多糖诱导小鼠急性肝衰竭模型。12h后处死小鼠,检测两组小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL)水平,取肝组织进行HE染色观察肝脏病理形态学改变。采用ELISA法检测小鼠血清及肝脏、脾脏、小肠组织中的PTX3、HBP、PCT及IL-6、IL-1β、TNF-α的水平。采用受试者工作特征(ROC)曲线分析各指标的诊断价值。结果ALF模型组小鼠较正常组小鼠肝组织结构破坏程度明显增加,炎性细胞浸润明显增多;血清AST、ALT、TBIL水平显著升高。模型组小鼠血清及肝脏、小肠组织中PTX3与正常小鼠比较明显升高,差异有统计学意义(P<0.05),但脾脏组织中PTX3水平比较,差异无统计学意义(P>0.05)。与正常组小鼠比较,模型组小鼠血清及肝脏、脾脏、小肠组织中HBP、PCT及IL-6、IL-1β、TNF-α均有升高,差异均有统计学意义(P<0.05)。ROC曲线分析PCT的诊断效能最高,其曲线下面积(area under the curve,AUC)为0.941,cut-off值为35.2pg/ml,敏感度为93.8%,特异性为87.5%;PTX3其次,AUC为0.859,cut-off值为475.4pg/ml,敏感度为81.3%,特异性为87.5%;TNF-α的诊断效能最低,其AUC为0.695,cut-off值为54.5pg/ml,敏感度为68.8%,特异性为62.5%。结论PTX3、HBP、PCT可用于早期急性肝衰竭的辅助诊断,且较IL-6、IL-1β、TNF-α诊断效能高。

Objective To explore the significance and diagnostic value of serum and tissue pentraxin 3(PTX3),heparin-binding protein(HBP),procalcitonin(PCT),interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)levels in acute liver failure(ALF)mice.Methods Totally 32 male mice were randomly divided into normal group and model group,16 mice in each group.D-galactosamine combined with lipopolysaccharide was used to induce mice model of acute liver failure.After 12 hours,the mice were sacrificed and the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBIL)in the two groups were detected.Liver tissues were taken for HE staining to observe the pathological and morphological changes.The levels of PTX3,HBP,PCT,IL-6,IL-1βand TNF-αin serum,liver,spleen and small intestine of mice were detected by ELISA respectively.The diagnostic value of each index was analyzed by using ROC curve.Results Compared with the normal group mice,ALF model group mice showed serious tissue damage and inflammatory cell infiltration.Serum AST,ALT and TBIL levels were significantly increased.The levels of PTX3 in serum,liver and small intestine of mice in the model group were significantly higher than those in normal mice,and the difference was statistically significant(P<0.05),but the level of PTX3 in spleen tissue was not statistically significant(P>0.05).Compared with the normal group,HBP,PCT,IL-6,IL-1βand TNF-αwere increased in serum,liver,spleen and small intestine of the model group(P<0.05).In the ROC curve analysis,PCT has the highest diagnostic efficiency,with an area under the curve(AUC)of 0.941,cut-off value of 35.218pg/ml,sensitivity of 93.8%and specificity of 87.5%.PTX3 was followed by 0.859 AUC,475.401pg/ml cut-off value,81.3%sensitivity and 87.5%specificity.TNF-αhas the lowest diagnostic efficacy,with an AUC of 0.695,cut-off value of 54.474pg/ml,sensitivity of 68.8%and specificity of 62.5%.Conclusion PTX3,HBP,PCT can be used for the auxiliary diagnosis of early acute liver failure,and the diagnosis efficiency is higher than IL-6,IL-1β,TNF-α.