摘要: 目的 探讨慢性萎缩性胃炎（CAG）病证结合大鼠肝组织病理及功能变化特征。方法 以雄性Wistar大鼠为实验材料，采用“四因素”综合造模法制备CAG病证结合大鼠模型。用实验动物证候综合评价量表分别采集造模第28周和40周大鼠的证候要素，同时抽检大鼠血清AST、ALT水平和肝组织病理变化。肝组织病理检测方法：冰冻切片经常规过碘酸-Schiff染色和硝基蓝四氮唑染色，分别显示肝细胞内糖原和琥珀酸脱氢酶（SDH）的分布；石蜡切片经HE染色观察肝组织病理学改变；超薄切片用透射电镜观察肝细胞超微结构的变化。结果 造模28周，CAG大鼠表现为脾气虚证型；造模40周，CAG大鼠出现脾虚为主、兼有血瘀的证型。与正常组比较，造模28周大鼠血清ALT和AST水平显著增高，差异有统计学意义(P<0.05)；造模40周，大鼠血清ALT水平仍显著增高(P<0.05)，而AST水平变化不显著(P>0.05)。组织病理学观察：造模28周时，肝细胞索排列紊乱，肝细胞肿胀；肝组织呈现斑状糖原缺失区，中央静脉周围肝细胞的SDH含量显著减少；透射电镜下，肝细胞内线粒体肿胀、变形，内质网减少，糖原颗粒减少，胞质内出现空泡样改变。造模40周，肝细胞萎缩，肝血窦变小，炎性细胞数量增多；肝组织糖原缺失区显著扩大，肝小叶大部分呈现SDH含量减少的趋势；透射电镜下，肝细胞内线粒体肿胀、膨大、数量显著减少，内质网显著减少，糖原颗粒数量显著减少。结论 CAG“四因素”综合造模法能成功制备CAG病证结合大鼠模型且大鼠肝脏功能和组织病理均有显著变化，表现为：转氨酶水平增高，肝糖原合成、储备减弱，线粒体肿胀、数量减少、氧化磷酸化功能减弱。
Abstract：Objective To observe hepatic pathological and functional changes in rat with chronic atrophic gastritis(CAG) in order to explore its mechanism.Methods Four comprehensive factors including N-methyl-N-nitro-nitrosoguanidine (MNNG), sodium salicylate, ranitidine and starvation were used to make model of CAG. The experiment groups were divided into control group and model group to observe the phenotype of rats at the 28th and 40th week after modeling and determine the syndrome. The level of AST and ALT in serum was measured by automated biochemical instrument. Hepatic pathological changes were observed by H&E staining; periodic acid-Schiff (PAS) reaction and transmission electron microscope (TEM). Results The rats showed spleen deficiency syndrome at 28th weeks after modeling, while the rats showed spleen asthenia and blood stasis at 40th week after modeling. Compared with the control group, the level of ALT and AST significantly increased at 28th week after modeling. The level of ALT still significantly increased at 28th week after modeling, while the level of AST was not significantly changed at 40th week after modeling. Compared with the control group, pathological changes indicated that hepatic cords were disorder and hepatocytes were swollen at 28th week after modeling while the hepatocytes were shrank, hepatic sinusoid became smaller and the amount of inflammatory cells increased at 40th weeks after modeling by HE staining; It is showed that synthesis and storage of glycogen both decreased at 28th and 40th weeks after modeling by PAS reaction; It is also showed that mitochondria in hepatocytes were swollen and denatured at 28th and 40th weeks after modeling by TEM. Conclusion The four-factor comprehensive modeling method can be used to establish the animal model of CAG. There were significant changes in liver function and histopathology in model group. These changes directly affect the balance of liver material metabolism and energy metabolism, and induce imbalance of physiological and biochemical function, which can partly explain the clinical manifestations of spleen deficiency syndrome in traditional Chinese medicine.