世界胃肠病学杂志(英文版)
世界胃腸病學雜誌(英文版)
세계위장병학잡지(영문판)
WORLD JOURNAL OF GASTROENTEROLOGY
2006年
28期
4504-4510
,共7页
Osteopenia%Liver disease%Portasystemic shunting%T-lymphocyte%Rapamycin
AIM: To study if T-cell activation related to portasystemic shunting causes osteodast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats.METHODS: Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated.RESULTS: Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFα,were not increased in serum and TNFα and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8+ T-cell population. Rapamycin decreased the circulating CD8+T-cell population, increased CD8+ CD25+ T-regulatory cell population and improved all parameters of bone turnover.CONCLUSION: Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.