Effects Of Carbachol On Cytokine Secretion And Organ Functions In Rabbit During Partial Ischemia-reperfusion Of Intestine

Many clinical and experimental studies have indicated that ischemia and reperfusoin(I/R)injury of the intestine plays a pivotal role in sepsis and multiple organ dysfunction syndrome (MODS) induced by trauma and shock. In this study, an animal model of multiple organ dysfunction with rabbits induced by partial I/R iniury in intestine was created, which was consistent with clinical study. At the same time, the levels and functions of cytokines, and the effects of carbachol on cytokines and organ functions during partial I/R in rabbit were explored. All those help to provide experimental evidences for the therapy of I/R insult and MODS with carbachol.At first, we created an animal model of multiple organ dysfunction induced by partial I/R insult in rabbit. Adopting some instruments designed by our studying team to partially block (50%, lasting for 4 hours) superior mesentery artery (SMA) blood flow, we found the animal model could obtain the desired mortality and the incidence of multiple organs dysfunction and could result in multiple organ dysfunction and significant pathological injuries in different organs. The contents of TNF-a, IL-6 and IL-10 were increased in blood plasma and some different tissues during the period of partial I/R. The contents of these cytokines were significantly higher in intestine versus other tissues, which suggested the intestine was one of the organs secreting massive cytokines. Cytokines secreted by intestine further stimulate the release of cytokines in other tissues. Excessive cytokines might ultimately lead to theoccurrence of systemic inflammatory response syndrome (SIRS) or MODS.Carbachol in the dose of 2.5 g/kg was injected into rabbit intestine at 2 hours after the SMA occlusion. As a result, the contents of TNF- , IL-6 and IL-10 were markedly decreased in blood plasma and some different tissues. The results of cell cultured in vitro also showed that carbachol could decrease the secretory levels of some cytokines. Simultaneously, we also found that the contents of GPT, CK-MB, Crm D- lactic acid and the activity of DAO were apparently reduced in blood plasma, and pathological appearance were alleviated in intestine, lung and liver of rabbits after administration of carbachol. The results of this study revealed that carbachol could inhibit the release of some cytokines and alleviate injuries of the function and structure of some different organs. Therefore, carbachol could be used to cure intestine inury and MODS caused by I/R.