胰岛素抵抗大鼠血糖正常阶段肝脏早期纤维化的观察

Early liver fibrosis in insulin resistant rats at normal blood glucose stage

目的研究胰岛素抵抗(IR)大鼠血糖正常阶段肝脏的形态学改变。方法高糖高脂饲料(2H)和高糖高脂高盐(3H)饲料喂养SD大鼠4月,复制IR大鼠模型,普通饲料喂养的SD大鼠为正常对照,用HE、VG染色光镜和透射电镜下观察肝脏形态学变化。结果2H组出现弥漫性肝细胞脂肪变性,肝小叶内有炎细胞浸润,肝窦周围、汇管区见红染的胶原纤维。3H组发现肝索排列紊乱,肝细胞点状坏死,炎细胞浸润;弥漫性肝细胞脂肪变性,大小不一的脂滴呈弥漫性聚集在肝细胞内,脂褐素沉积。肝细胞间、肝窦周围、汇管区见大量红染的胶原纤维。2H组和3H组透射电镜观察发现肝Kupffer细胞增生,肝细胞胞质内有许多大小不一的脂滴,Disse间隙内胶原纤维多见,有淋巴细胞、浆细胞活化增生,另外,观察到浆细胞和肝星状细胞联系紧密。结论IR大鼠血糖正常阶段肝脏已有早期纤维化现象,可能与免疫系统激活有关。

Objective To investigate the morphological changes of liver in insulin-resistant （IR） rats at normal blood glucose stage. Methods Insulin-resistant rats model（n = 10 × 2） were reproduced from 2 months old Sprague- Dawley （SD） rats by high-glucose and fat diet （2H） or high-glucose,fat and salt diet（3H） for 4 months,respectively. Normal diet SD rats （ n = 10） were taken as the control group （CN）. HE and VG staining were used to demonstrate the pathological changes,and transmission electron microscope （TEM） was used to observe the ultrastructure of hepatic tis- sues. Results 2H group appeared diffuse hepatocyte steatosis and inflammatory cell infiltrated in hepatic lobule. Stained red proliferated collagen fibers were observed surrounding hepatic sinusoid and portal areas. 3H group showed that hepatic cord arranged irregularly. Hepatocyte had pointing necrosis, inflammatory cell infiltrated. Diffuse hepatocyte steatosis and lipofuscin deposition displayed in hepatocyte. Lipid droplets were different in size. Proliferated collagen fi- bers were seen between neighbor hepatocytes and around hepatic sinusoid and portal areas. TEM demonstrated that Kupffer cells increased and many various lipid droplets displayed in hepatocytes of 2H and 3H groups. Proliferated colla- gen fibers were seen frequently in Disse space. Lymphocytes and plasma cells activated and proliferated. Moreover, Plasma cells and hepatic stellate cells （HSC） contacted tightly. Conclusion Early liver fibrosis is found in IR rats at normal blood glucose stage. It may be associated with activation of immune system.