The Clinical And Experimental Study Of Rhubarb On Gut-original Sepsis In Critical Illness

Gut-liver-lung axis is very important for gut-original sepsis in critical illness. The liver and lung are able to amplify gut-original septic response and 'make sepsis un-controllable. The hypothesis of this study is that rhubarb can inhibit gut-liver-lung axis and make systemic inflammatory response syndrome from uncontrollable to controllable, which reverses pathophysiological response of SIRS and prevent development of MODS.The animal model, which could develop gut-original sepsis, were used in this study. The results revealed that hemorrahgic shock resulted in bacterial translocation and endotoxin absorption. Rhubarb was able to inhibit bacterial translocation, lower the level of endotoxin in the plasma, and improve the blood perfusion in intestinal mucosa in shocked rats. Histopathology revealed that rhubarb alleviated the intestinal injury caused by the shock and promoted the reproduction of the goblet cells in the villi.Burn plus endotoxin second hit up-regulated the expression of TNF- a and IL-1 genes in the liver of rats. Whereas rhubarb inhibited the expression of TNF- a ,IL-1 in the liver . Hybridization in situ revealed that thermal injury and the second hit obviously increased the expression of TNFR1 and TNFR2 genes in hepatic cells. However, the rhubarb down-regulated both of the receptors. In addition, there was very high level of TNF- a in the plasma and hepatic tissues after thermal injury and the second hit, especially in the hepatic tissues. Rhubarb evidently lowered the concentration of TNF- a in the plasma and hepatic tissues. The level of energy charge in the hepatic mitochondria was decreased after burn injury, and deteriorated further after the second hit by endotoxin on a time manner. Whereas, rhubarb could obviously increase the level of energy charge in the hepatic mitochondriaThe model, which underwent intestinal ischemia -reperfusion, revealed that rhubarb evidently inhibited the accumulation of neutrophils in the lung, improved the pulmonary microvascular permeability, and decreased the level of TNF, PLA2 and NO in pulmonary tissues.Clinical study revealed that incidence of stress ulceration, gastrointestinal paralyses and multiple organ dysfunction syndrome was obviously lower in preventive rhubarb treatment group than that in non-preventive group. Moreover, rhubarb had good curative effects on stress ulceration, toxic gastrointestinal paralyses caused by sepsis. Furthermore, rhubarbdramatically improved the gastrointestinal blood perfusion and reduced the level of TNF-a , IL-6 and endotoxin in the plasma in MODS patients. In addition, it also inhibited the expression of TNF- a genes in systemic blood. The survival rate in the MODS patients, whose dysfunction organs were involved more than four ones, was much higher in rhubarb therapy group than those in non-rhubarb treatment group.In conclusion, rhubarb can protect gut barrier, inhibit the gut-original septic response in the liver, lung and systemic blood, and interdict gut-liver-lung axis.