大鼠肝纤维化病理分期与肝纤维化血清标志物相关性研究

The Relationship between the Pathological Degree of Fibrosis and Serum Hepatic Fibrosis in HF Rats

目的:研究肝纤维化病理组织学分期与血清纤维化标志物门冬氨酸氨基转移酶(AST)与血小板(PLT)比值指数(APRI)、透明质酸(HA)及基质金属蛋白酶抑制物(TIMP-1)的相关性,以探讨非创伤性检测血清蛋白和联合分析血清纤维化标志物的诊断价值。方法:将75只成年健康的SD大鼠采用改良式复合因素法构建大鼠肝纤维化模型,分别在5、6个周后,进行大鼠肝脏穿刺活检病理学组织检查,HE、Masson染色后进行病理组织学分期,同时检测大鼠血清门冬氨酸氨基转移酶(AST)与血小板(PLT)比值指数(APRI)、透明质酸(HA)及基质金属蛋白酶抑制物(TIMP-1)水平。结果:肝脏组织病理学检查发现肝纤维化的分期与炎症活动程度呈明显的正相关(P<0.05)。而对于区分显著肝纤维化(≥S2)血清标志物指标诊断纤维化的ROC曲线分析发现,HA、TIMP-1、APRI曲线下面积分别为0.921、0.732、0.905。HA+APRI联合诊断灵敏度为84.1%,特异度为91.2%。TIMP-1+APRI联合诊断灵敏度为83.2%,特异度为91.7%。结论:利用检测血清纤维化标志物这种对患者无创的检测方法虽不能完全取代病理学活检,但预测肝纤维具有一定的诊断价值,当联合分析两种血清纤维化标志物时,灵敏度和特异度都比单独分析一种标志物要高。

Objective： To study the relarationship between the histopathological degree of liver fibrosis and serum fibrosis markers, aspartate aminotransferase （AST） and platelet （PLT） ration index （APRI）, hyaluronic acid （HA） and matrix metalloproteins inhibitor （TIMP-1）, in order to investigate the diagnostic value of the non-invasive detection of serum proteins and associated analysis of serum fibrosis markers. Methods： 75 healthy adult SD rats were duplicated with Improved Composite Factor Method. After 5 or 6 weeks, rats were treated with liver biopsy for HE/Massion staining to degree the fibrosis, and detected APRI, HA, TIMP-1. Results： It is positive correlation between inflammation activity and the degree of hepatic fibrosis. To distinguish ≥ S2 from no fibrosis, HA, TIMP-1 and APR/ gave the ROC of 0.921, 0.732, 0.905. Combining the aspartate aminotransferase （AST） to platelet ratio index （APRI） and HA/100 showed the sensitivity of 84.1% and specificity of 91.2 %. Combining APRI and TIMP-1/100 showed the sensitivity of 83.2 % and specificity of 91.7 %. Conclusion： The non-invasive methods analyzing serum fibrosis markers of patients can not completely replace the liver biopsy, but has great value in predicting liver fibrosis. When combined analyzing two serum fibrosis markers, the sensitivity and specificity is increased, compared with analyzing one serum fibrosis marker.