The Protective Effect Of Dexmedetomidine On Intestinal Injury In Septic Rats

Objective: To verify whether dexmedetomidine(DEX) can attenuate sepsis induced intestinal injury via inhibition of inflammation. Methods: Male SD rats were randomly assigned to four groups(n=16 each): a sham group(Sham), a model group(CLP), a DEX group(DEX), and a DEX plus yohimbine(YOH) group(DEX+YOH). Rats in groups of CLP, DEX, DEX+YOH were established cecum ligation and puncture(CLP) model, but the cecums were just isolated without ligation or puncture in Sham group. Rats in DEX group were injected with DEX(5μg·kg-1·h-1) 0.5h after CLP for 1h via tail vein, however, YOH(1.0mg/kg) was injected prior to DEX treatment in DEX+YOH group. Rats in groups of Sham and CLP received equal volume of saline during the same period. At 12 h, 24 h after cecum surgery, serum and intestinal tissues(8 rats for each group) were harvested. Histological damage was observed by optical microscopy. Levels of serum DAO, D-lactate were determined by spectrophotometry, and, levels of TNF-α, IL-1β, IL-6 in serum and tissues were detected by ELISA. The expressions of Occludin and TLR4 in tissues were measured by western blotting. For the survival studies, 40 rats in total(n=10 in each group) were conducted as above. The normal behaviors and 7 days survival rate after surgery were monitored. Results:(1) Histology changes of intestines were obvious, DAO, D-lactate levels were obviously increased and Occludin expression was reduced, the expressions of TNF-α, IL-1β, IL-6, TLR4 were also increased in groups of CLP, DEX, DEX+YOH(P<0.05 vs. Sham) at 12 h and 24 h. In groups of DEX, DEX+YOH, histology changes were minor, DAO, D-lactate levels were attenuated and Occludin expression was increased, the expressions of TNF-α, IL-1β, IL-6, TLR4 were also decreased(P<0.05 vs. CLP). The distinctions between CLP and DEX+YOH groups in terms of intestinal TNF-α at 12 h or IL-1β at 24 h did not show statistical significance(P>0.05). Moreover, histopathology lesion of intestines was obvious, DAO, D-lactate levels were increased and Occludin expression was reduced, the expressions of TNF-α, IL-1β, IL-6, TLR4 were also increased in DEX+YOH group(P<0.05 vs. DEX).(2) The mortality rates were evidently increased in groups of CLP, DEX +YOH, respectively(P<0.05 vs. Sham), but it was not elevated significantly in DEX group(P>0.05 vs. Sham), and, the mortality rate was apparently decreased in DEX group(P<0.05 vs. CLP), but it didn’t change significantly in DEX + YOH group(P>0.05 vs. CLP). The mortality rate was also obviously increased in DEX + YOH group compared with DEX group(P<0.05). Conclusion: Our study indicated that DEX could be able to significantly reduce sepsis-induced intestinal injury, and which may be associated with the inhibition of inflammation via α2–adrenergic receptor.