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Chronic biliary drainage corrects liver atrophy induced by portacaval shunt in the rat
GASTROENTEROLOGY
1981;80:1023-30
Chronic Biliary Drainage Corrects Liver Atrophy Induced by Portacaval Shunt in the Rat PAULETTE BIOULAC, LILIANE DUBUISSON, JEAN SARIC, LILIANE DESPUYOOS, CHRISTIANE BEDIN, FRANCOISE MAGNE, and CHARLES BALABAUD Centre de Microscopic Electronique, Institut de Recherche Experimentale and Laboratoire des Interactions Cellulaires, Universite de Bordeaux II, France
Portacaval shunt induces a severe liver atrophy. The relative liver hypertrophy induced by chronic biliary drainage was studied by electron microscopy. Rats with either portacaval or sham portacaval shunt had a &day chronic bile fistula. Compared with rats not submitted to chronic bile fistula, liver weight/ body weight ratio increased from 1.84 f 0.12 to 3.54 + 0.48 (p < 0.05) in portacaval shunt and from 3.52 f 0.15 to 3.64 f 0.40 (p < 0.05) in sham portacaval shunt (controls). Chronic bile fistula stimulated bile acid synthesis in the two groups. Furthermore, the initial low bile flow observed in portacaval shunt (rats) reached control values after chronic bile fistula. Ultrastructural abnormalities observed in portacaval shunt: atrophy of the hepatocyte mainly related to the atrophy of the rough and smooth endoplasmic reticulum, irregularity of the nucleus, dilatation of the nuclear envelope and of the rough endoplasmic reticulum, and swelling of mitochondria, were greatly modified by chronic bile fistula. The hepatocyte size increased, mitochondria appeared smaller than normal, the nuclear envelope and the rough endoplasmic reticulum were not dilated, and the rough and smooth endoplasmic reticulum were expanded. Chronic bile fistula had no noticeable effect on the liver in sham portacaval shunt. Either stimulation of bile salts synthesis or removal of bile salts, which could be toxic for the atrophic
Received November 19, 1979. Accepted December 28, 1980. Address requests for reprints to: Charles Balabaud, M.D., Laboratoire des Interactions Cellulaires, Universite de Bordeaux II, 33076 Bordeaux, France. This work was supported by grants from the Universite de Bordeaux II. The authors wish to thank Pierre Gonzalez for dedicated technical assistance and Claudette Delphy and Genevieve Baron for their help in preparing the manuscript. 0 1981 by the American Gastroenterological Association 0016-5085/81/051025-08$02.50
liver,
are possible
pertrophy
explanations of the liver.
for the relative
hy-
Portacaval shunt (PCS) induces a severe liver atrophy in rats. Reduced hepatic blood flow and lack of hepatotrophic factors are considered to be the main causes of liver atrophy (1). Two weeks after PCS, hepatocytes are of small size and ultrastructural damage described by several authors (2-5) predominate in the periportal zone (6). In this model, few studies have been devoted to bile secretion (7-9). We observed recently that chronic biliary drainage in rats with PCS corrects liver atrophy (10). The aim of the present work was to assess morphologic liver changes induced by bile drainage in rats with and without PCS
Materials and Methods Materials Male Wistar rats weighing 250-300 g were used. They had normal access to food (A03, U.A.R., Villemoisson sur Orge, France) and water. Animals housed in plastic cages with woodchip litter were maintained on an artificial day light cycle. The temperature and humidity were maintained constant. Terminal PCS were performed (11) under ether anesthesia with clean but not sterile instruments. Rats were then housed in individual metallic cages equipped with screens to avoid coprophagy. Other conditions were as above. Two to three weeks later, the animals were either killed with pentobarbital sodium (Abbott Laboratories, SaintRemy-sur-Ayre, France) anesthesia (25 mg/kg) or equipped with a chronic bile fistula (CBF) (12) under methohexital (Eli Lilly, Indianapolis, Ind.) anesthesia. The latter group received i.p. 0.5 &i of [‘%]cholic acid (New England Nuclear, Boston, Mass.) 24 h before surgery. Unrestrained rats were housed as before with free access to
food and tap water but in addition had free access to Ringer fluid. Bile was collected every hour for the first 24 h
1981;80:1023-30
Chronic Biliary Drainage Corrects Liver Atrophy Induced by Portacaval Shunt in the Rat PAULETTE BIOULAC, LILIANE DUBUISSON, JEAN SARIC, LILIANE DESPUYOOS, CHRISTIANE BEDIN, FRANCOISE MAGNE, and CHARLES BALABAUD Centre de Microscopic Electronique, Institut de Recherche Experimentale and Laboratoire des Interactions Cellulaires, Universite de Bordeaux II, France
Portacaval shunt induces a severe liver atrophy. The relative liver hypertrophy induced by chronic biliary drainage was studied by electron microscopy. Rats with either portacaval or sham portacaval shunt had a &day chronic bile fistula. Compared with rats not submitted to chronic bile fistula, liver weight/ body weight ratio increased from 1.84 f 0.12 to 3.54 + 0.48 (p < 0.05) in portacaval shunt and from 3.52 f 0.15 to 3.64 f 0.40 (p < 0.05) in sham portacaval shunt (controls). Chronic bile fistula stimulated bile acid synthesis in the two groups. Furthermore, the initial low bile flow observed in portacaval shunt (rats) reached control values after chronic bile fistula. Ultrastructural abnormalities observed in portacaval shunt: atrophy of the hepatocyte mainly related to the atrophy of the rough and smooth endoplasmic reticulum, irregularity of the nucleus, dilatation of the nuclear envelope and of the rough endoplasmic reticulum, and swelling of mitochondria, were greatly modified by chronic bile fistula. The hepatocyte size increased, mitochondria appeared smaller than normal, the nuclear envelope and the rough endoplasmic reticulum were not dilated, and the rough and smooth endoplasmic reticulum were expanded. Chronic bile fistula had no noticeable effect on the liver in sham portacaval shunt. Either stimulation of bile salts synthesis or removal of bile salts, which could be toxic for the atrophic
Received November 19, 1979. Accepted December 28, 1980. Address requests for reprints to: Charles Balabaud, M.D., Laboratoire des Interactions Cellulaires, Universite de Bordeaux II, 33076 Bordeaux, France. This work was supported by grants from the Universite de Bordeaux II. The authors wish to thank Pierre Gonzalez for dedicated technical assistance and Claudette Delphy and Genevieve Baron for their help in preparing the manuscript. 0 1981 by the American Gastroenterological Association 0016-5085/81/051025-08$02.50
liver,
are possible
pertrophy
explanations of the liver.
for the relative
hy-
Portacaval shunt (PCS) induces a severe liver atrophy in rats. Reduced hepatic blood flow and lack of hepatotrophic factors are considered to be the main causes of liver atrophy (1). Two weeks after PCS, hepatocytes are of small size and ultrastructural damage described by several authors (2-5) predominate in the periportal zone (6). In this model, few studies have been devoted to bile secretion (7-9). We observed recently that chronic biliary drainage in rats with PCS corrects liver atrophy (10). The aim of the present work was to assess morphologic liver changes induced by bile drainage in rats with and without PCS
Materials and Methods Materials Male Wistar rats weighing 250-300 g were used. They had normal access to food (A03, U.A.R., Villemoisson sur Orge, France) and water. Animals housed in plastic cages with woodchip litter were maintained on an artificial day light cycle. The temperature and humidity were maintained constant. Terminal PCS were performed (11) under ether anesthesia with clean but not sterile instruments. Rats were then housed in individual metallic cages equipped with screens to avoid coprophagy. Other conditions were as above. Two to three weeks later, the animals were either killed with pentobarbital sodium (Abbott Laboratories, SaintRemy-sur-Ayre, France) anesthesia (25 mg/kg) or equipped with a chronic bile fistula (CBF) (12) under methohexital (Eli Lilly, Indianapolis, Ind.) anesthesia. The latter group received i.p. 0.5 &i of [‘%]cholic acid (New England Nuclear, Boston, Mass.) 24 h before surgery. Unrestrained rats were housed as before with free access to
food and tap water but in addition had free access to Ringer fluid. Bile was collected every hour for the first 24 h