Background: The role of Kupffer cells (KCs) in nonalcoholic steatohepatitis (NASH) which is regarded as a major cause of cryptogenic cirrhosis of the liver was investigated using stereological methods and electron microscopy in the rat model. To our knowledge, there is no stereological study on the volume of liver, total number, numerical density, and nuclear height of KCs of liver in the female rat fed with a high fat diet (HFD) in the literature.
Method: 16 female Sprague Dawley rats were randomized into HFD and control group, with HFD and standard diet for 12 weeks, respectively. In this study, two basic research methods were used to analyze the samples. One was histopathological observation at both light and electron microscopic level. The other was stereological methods that consist of Cavalieri principle for liver volume estimation and physical disector method for estimation of numerical density and total number of KCs in the liver.
Results: Liver volume, both mean numerical density and total number of KCs, were statistically increased in HFD rats. Ultrastructurally, a significant decrease in the mean nuclear height of KCs in HFD rats was also found. In the control group, no abnormal change was observed, but in the HFD group, some changes such as diffuse steatosis, mononuclear cell infiltration, necrosis, fibrosis, accumulation of fat droplets and intra-cytoplasmic vacuoles, and swollen mitochondria with irregular membranes were observed in the hepatocytes.
Conclusion: The number and activity of KCs are increased significantly in NASH induced by HFD, and KCs might be involved in the pathogenesis of steatohepatitis as previously attributed as a major cause of cryptogenic cirrhosis of the liver.