Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I

BACKGROUND: Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis. METHODS: Advanced cirrhosis was induced by CCl(4 )inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using (14)C or (35)S-labelled subtracts in the three experimental groups. RESULTS: Intestinal active Na(+)-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased V(max )and a reduced affinity for sugar and four amino acids transporters (expressed as an increased K(t)) in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy. CONCLUSIONS: The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids) are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I

Postnatal epithelial growth of the small intestine in the rat occurs by both crypt fission and crypt hyperplasia

Studies of growth of the small intestine have largely concentrated on crypt hyperplasia rather than crypt fission. The aim of this study was to investigate quantitatively both crypt fission and crypt hyperplasia. DAxPVG/c rats were killed at 7, 11, 14, 17, 19, 21, 25, 55, and 72–73 days of life. Samples of jejunum at one third of the intestinal length were taken for morphometry (villous area, crypt area, percentage of bifid crypts, and crypt mitotic count) by microdissection. Growth factors and their receptors were assessed by oligonucleotide microarray. Crypt fission was 10.5%, 5.2%, and 1.5% at days 11, 25, and 72–73 of life, respectively. Crypt hyperplasia increased from day 21. No conventional growth factor was identified during crypt fission. We conclude that crypt fission contributes to growth of the small intestine prior to weaning and crypt hyperplasia to growth after weaning.Adrian G. Cummins, Ben J. Jones, and Fiona M. Thompso