Electron Microscopic Observation on the Degradation and Resorption of Collagen Fibers in Experimental Hepatic Fibrosis

Abstract

The present study was designed to investigate some role of hepatocytes and mesenchymal cells in the process of resorption of collagen fibers in experimental hepatic fibrosis. The exprolatory laparotomy was performed on the female Wistar strain rats, which had been subjected to subcutaneous injection of carbon tetrachloride for 4 to 12 weeks, to get a small piece of liver tissue for morphological and enzymohistochemical study. Carbon tetrachloride administration was discontinued, and 1 to 3 weeks thereafter the animals were sacrificed. The broad fibrous septa in the liver as a result of the continued carbon tetrachloride administration were rarefied and collagen fibers proliferated around degenerated hepatocytes, especially in the perisinusoidal spaces, has almost disappeared 3 weeks after the discontinuation of carbon tetrachloride administration. The hepatic cells facing to the site of collagen fiber proliferation showed a flattening and/or disappearance of microvilli and irregular deposition of ruthenium red positive material coating hepatic cell surface. The organelles of these hepatic cells appeared degenerated with a marked decrease of primary lysosomes. These abnormal findings have disappeared in almost parallel with the disappearance of the newly formed collagen fibers as well as ruthenium red positive material.
The enzymohistochemical study revealed a markedly decreased activity of lysosomal enzymes both in hepatocytes and mesenchymal cells in the advanced stage of hepatic fibrosis. In the recovery stage the enzymatic activity in the hepatocytes and mecenchymal cells appears almost normal. Ultrastructural findings suggested that the collagen fibers would be degraded mainly in the extracellular process, and some fibers first degraded extracellularly to a certain extent would be engulfed by Kupffer cells and/or macrophages.
It is surmised that the fusion of the primary lysosomes with the phagosome which has enveloped the degraded pieces of collagen fibers will accelerate the decomposition and hydrolysis of the denatured collagen.