Irreversible Exocrine Pancreatic Insufficiency in Alcoholic Rats Without Chronic Pancreatitis After Alcohol Withdrawal

Authors

  • Jing Li,

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author
  • Chao Zhou,

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author
  • Rui Wang,

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author
  • Rui Liu,

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author
  • Zhiyin Huang,

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author
  • Chengwei Tang

    1. From the Department of Gastroenterology, West China Hospital (JL, CZ, CT), Sichuan University; and Division of Peptides Related with Human Diseases (JL, RW, RL, ZH, CT), Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, Chengdu, China.
    Search for more papers by this author

Reprint requests: Professor Chengwei Tang, Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China; Tel.: +86 28 85422383; Fax: +86 28 85422351; E-mail:chengweitang@163.com; cwtang@medmail.com.cn

Abstract

Background:  Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.

Methods:  Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.

Results:  Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors.

Conclusions:  Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.

Ancillary