[Effects of carbachol on apoptosis of peripheral white blood cells and expression of cytokines in rats suffering from gut ischemia/reperfusion injury].

Objective: To evaluate the effect of cholinergic drug carbachol on apoptosis and expression of certain cytokines of peripheral blood lymphocytes and neutrophils in rats subjected to ischemia/reperfusion injury of the intestine.

Methods: Thirty-six Wistar male rats were randomly divided into groups as follows: sham operation, 1 and 2 hour-gut ischemia, 1 hour-gut ischemia followed by reperfusion for 1 hour and 2 hours, carbachol + 1 hour-gut ischemia, and carbachol + 1 hour-gut ischemia followed by reperfusion for 2 hours. Then the gut was subjected to ischemia/reperfusion. At different time points after the said injury, the total number and differential count of leukocytes, apoptosis rate of lymphocytes and neutrophils, and the mRNA expression levels of certain cytokines in peripheral blood leukocytes, were determined.

Results: At 1 hour after gut ischemia, the total number of leukocytes decreased (the ratio of lymphocytes increased and that of neutrophils decreased), but it increased after gut reperfusion. Carbachol could reduce the apoptosis rate of lymphocytes, but enhance that of neutrophils after gut ischemia. In leukocytes, mRNAs expression of inflammatory (TNF-alpha) and antiinflammatory (IL-10) cytokines were upregulated at 1 hour after gut ischemia, while that of IL-10, IL-4 and interferon-gamma were down-regulated distinctly at 2 hours following reperfusion. All of these phenomena were ameliorated by giving carbachol.

Conclusion: Carbachol could reduce the peripheral lymphocytes apoptosis subsequent to gut ischemia, and regulate the balance between inflammatory and antiinflammatory cytokines expression in leukocytes during gut ischemia and reperfusion. The results suggest that carbachol might be a potential therapeutic agent in preventing uncontrolled inflammatory response as a result of ischemia/reperfusion injury of the intestine.