Objective    To investigate the protective effects of microencapsulated adenovirus-mediated gene transfer of Bcl-2 on intestinal mucosa in rats after ischemia-reperfusion injury and underlying mechanism.     Methods    Alginate microcapsules containing the recombinant adenovirus AdCMV/Bcl-2 was prepared by using air atomization technique. Its acid resistance and dissolution in intestinal fluid were tested in artificial gastric juice and intestinal fluid. After the microencapsulated adenovirus (5×10

9

PFU) were inje

cted by venous and intraperitoneal injection

and oral taking into the rats in 48 h before ligating superior mesenteric artery for 1 h followed by reperfusing for 6 h (ischemia-reperfusion injury)

the expression of Bcl-2 in intestinal mucosa was detected by RT-PCR and Western blot analysis. The protective role of Bcl-2 in the intestinal mucosa in rats was analyzed by measuring plasma levels of endotoxin

D-lactic acid

and DAO.     Results    The recombinant adenovirus AdCMV/Bcl-2 contained in microcapsules was still survivable in vitro and also could  transfect and proliferate in 293 cells.The prepared microcapsule was almost insoluble in the simulated gastric juice but soluble in the simulated intestinal fluid in which the solution ratio arrived to 57.2% at 40 min. The AdCMV/Bcl-2 transfection in vivo successfully induced Bcl-2 over-expression in the intestinal mucosa

which protected the intestinal mucosa against ischemia and reperfusion injury. The AdCMV/Bcl-2 transfection in vivo attenuated intestinal epithelial cell apoptosis and structural mucosal damages

and decreased plasma endotoxin

DAO and D-lactic acid content following ischemia and reperfusion.     Conclusion    The AdCMV/Bcl-2 transfection in vivo successfully induces Bcl-2 over-expression in the intestinal mucosa

and protects the intestinal mucosa against the ischemia and reperfusion injury through attenuating intestinal epithelial cell apoptosis and decreasing plasma contents of endotoxin

D-lactic acid

and DAO. The microencapsulated adenovirus taken orally circumvents the injury in the stomach and exerts protective effect during the ischemia and reperfusion injury in intestinal mucosa. Our results suggest the microcapsulation of adenovirus might provide an effective means for the gene therapy in clinical application.