摘要目的 观察二甲基亚硝胺(DMN)诱导大鼠致肝纤维化的组织病理学改变,并采用半定量方法探讨肥大细胞和肝纤维化之间的关系.方法 Wistar系雄性大鼠72只,对照组和正常组各16只,实验组40只,实验组大鼠在一次性注射DMN后2周至12个月,在8个时间点分别取大鼠肝脏,通过特殊染色、免疫组织化学(ABC法)染色及电镜等方法,测量纤维化面积率和纤维化灶内的肥大细胞数量,观察肥大细胞的基质金属蛋白酶2( MMP-2)和金属蛋白酶组织抑制因子(TIMP-2)的表达情况及各种相关细胞的超微结构改变.结果 注射DMN后肝脏所形成的纤维化面积率于2周(3.72％)和1个月(3.73％,P=0.2626)时最明显,之后逐渐下降,直到12个月(1.42％,P=0.0003)肝组织内仍残留少许.肥大细胞于注射DMN后2周(200倍光镜下平均每视野1.73个)开始出现,于4个月(3.06个,P=0.008)时达到高峰,之后逐渐下降,但12个月(1.04个,P=0.045)时也仍可见少量.此模型中形成的纤维化和浸润的肥大细胞数量不成比例,高峰期不平行.肥大细胞表达MMP-2,但不表达TIMP-2.结论 在DMN诱导的肝纤维化大鼠模型中,肥大细胞不仅参与肝纤维化的形成,还可能通过合成分泌MMP-2参与纤维化的降解.

abstractsObjective To investigate the relationship between mast cell and hepatic fibrosis by histopathological method and semi-quantitative measurement.Methods Seventy-two Wistary male rats,the control group and the normal group of each only 16,experimental group of 40 rat liver fibrosis was induced by injection of DMN and was sampled at eight different time points. HE, histochemistry,immunohistochemistry (ABC method) and immunofluorescence were performed.The size of fibrosis and the number of mast cells were counted.The expression of MMP-2 and TIMP-2 was documented and electron microscopic examination was performed.Results After injection of DMN,the fibrosis was the most severe in the 2 week ( 3.72％ ) and the first month ( 3.73％,P =0.2626 ),and then gradually diminished,although residual fibrosis was still present at 12 months ( 1.42％,P =0.0003 ).The appearance of mast cells began at 2 weeks ( 1.73 per 200 power field in average by light microscope) after the injection and reached the peak at 4 months (3.06,P =0.008).Residual amount of mast cells were present at 12 months ( 1.04,P =0.045 ).However,the degree of fibrosis was not proportional or overlapping with the number of mast cells in this experiment model. Mast cells expressed MMP-2 but not TIMP-2. Conclusions In the DMN-induced rat liver fibrosis model,mast cell may be an integral player in the pathogenesis of liver fibrosis and may contribute to the degradation of fibrosis by synthesizing and secreting MMP-2.