Ultrastructural Changes of Fat-storing Cells in Experimental Hepatic Fibrosis

실험적 간섬유화에서 Fat-storing Cell의 미세구조의 변화에 대한 연구

Hepatic fibrosis was induced in Sprague-Dawley rats to evaluate the ultrastructural changes of fat-storing cells(Ito cells). For experimental induction of liver fibrosis, the rats were administered intraperitoneally with 0.5ml of 50% $Ccl_4$ solution per Kg body weight, twice weekly for 12 weeks. The rats were sacrified every week. The liver tissues were examined under light and eletron microscopes. And the immunohistochemical study of desmin was also performed. The results were summarized as follows : Light microscopic findings : The cellular infiltrations with inflammatory cells and Kupffer cells developed from 1 week after $Ccl_4$ injection, and were the most severe in 4 weeks. The strong immunoreactivity for desmin was also evident in 4 weeks. The centrilobular necrosis and fibrosis developed from 2 weeks after injection, and the necrosis persisted until 8 weeks. The progress of fibrosis was accompanied by decreases in cellular infiltration and reactivity for desmin, and increased gradual nodular formation was also observed. The cirrhosis was developed after 10 weeks. Electron microscopic findings : An increase in number of fat-storing cells was observed from 1 week after injection. Transitional cells characterized by a depletion of lipid droplets and a hypertrophy of the rER appeared after 2 weeks. The number of transitional cells with abundant collagen fibers in the extracellular spaces increased in 4 weeks. With progression of fibrosis the number of fat-storing cells decreased and proliferating fibroblasts with dilated rER were observed. According to these results it was revealed that there was an apparent transition from fat-storing cells to transitional cells and to fibroblasts. These cells had a few similar characteristics and may belong to the same cell population. Thus it was suggested that fat-storing cells might play an important role in hepatic fibrosis.

간 섬유화에서 fat-storing cell의 변화를 미세 구조학적 측면에서 관찰하고자, 사염화탄소를 mineral oil에 녹여 1 : 1로 회석한 후 Kg당 0.5 ml의 용량을 주 2회씩 12주간 흰쥐에 복강 주입하였다. 실험기간 동안 1주 간격으로 도살하고, 적출된 간조직을 광학현미경과 연역조직화학적 검사 및 전자현미경으로 관찰하여 다음과 같은 결과를 얻었다. 광학현미경적 소견상 소엽 중심주의 염증 반응 및 세포 침윤 현상은 사염화탄소 투여 후 1주부터 나타나서 4주 째 가장 심하였으며, 이시기에 desmin염색 반응 양성세포의 수도 증가되었다. 괴사 및 섬유화는 2주부터 나타나기 시작하여 6주부터 결절이 형성되기 시작하였고 괴사성 병변은 8주까지 지속되었다. 그러나 세포 침윤 정도는 감소되면서 desmin에 대한 반응성도 낮아졌고, 경변성 변화는 10주 이후부터 나타났다. 전자현미경적 소견상 fat-storing cell의 숫적 증가는 1주부터 관찰되었으며 지방적이 감소하고 rER이 팽창된 이행세포는 2주째 출현하여 4주에 가장 현저히 증가되었다. 섬유아세포는 3주부터 나타나기 시작하였는데, rER이 확장되었으며 지방적은 없거나 1-2개의 소적이 세포돌기에서 관찰되었다. 섬유화가 진행됨에 따라 이행세포 및 fat-storing cell은 감소하고 섬유아세포는 증가된 상태를 유지하였다. 이상의 결과로 보아 fat-storing cell은 간섬유화 과정에서 활성화되고 증식하여 형태학적으로 이행세포 및 섬유아세포로 전환함으로써, 정지상태에 있는 섬유아세포의 전구체로서 간섬유화에 중요한 역할을 하는 것으로 사료된다.