The sympathetic nervous system promotes carbon tetrachloride-induced livercirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes

Citation
K. Hamasaki et al., The sympathetic nervous system promotes carbon tetrachloride-induced livercirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes, J GASTRO, 36(2), 2001, pp. 111-120
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
JOURNAL OF GASTROENTEROLOGY
ISSN journal
0944-1174 → ACNP
Volume
36
Issue
2
Year of publication
2001
Pages
111 - 120
Database
ISI
SICI code
0944-1174(200102)36:2<111:TSNSPC>2.0.ZU;2-C
Abstract
Norepinephrine is considered to possess potent anti-apoptotic action in reg enerating hepatocytes. To clarify the role of the sympathetic nervous syste m in apoptosis that occurs in chronic liver damage and following the promot ion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced li ver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24h after CCl4 adminis tration, acute damage, characterized by vacuolated hepatocytes in the centr ilobular zone, was greater in SHR than in WKY. This vacuolated change in WK Y hepatocytes was significantly reduced by chemical sympathectomy with 6-hy droxydopamine (6-OHDA). After 48 h, the acute damage was dramatically impro ved in each animal, without significant differences between the three group s. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scan t fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, li ver cirrhosis was seen only in SHR. The incidence of apoptotic cells in are as of both acute and chronic damage in WKY, detected by terminal deoxynucle otidyl transferase-dUTP nick end labeling, was significantly increased in c omparison with that in SHR, and was further increased by 6-OHDA pretreatmen t. In contrast, there was significantly greater enhancement of the growth o f hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover , hepatocyte growth kinetics in WKY was significantly inhibited after sympa thectomy in acute injury, as evidenced by immunohistochemistry for prolifer ating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular a poptosis induced by transforming growth factor-beta1 was significantly decr eased by incubation with norepinephrine. These findings suggest that the an ti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.