| Backgroud:Intestinal system takes part in the pathology and physiology of shock and MODS, it is the hot topic of multidisciplinary study that the protective mechanism of intestinal and remote organ during intestinal ischemia-reperfusion (Ⅱ/R). As a kind of endogenous protective measure, the protection of ischemic postconditioning (IPO) for remote organ injury induced by II/R has been tentative confirmated by the domestic and foreign scholars. As the most important endogenous anti-oxidative stress pathway ever discovered, the key role of Nrf2-ARE signal pathway has been tentative confirmed in digestive system, circulation system, nervous system and Disease of immune system. However, the protection and mechanism of IPO on remote organ injury induced by II/R still await for futher investigation, the effect and mechanism of Nrf2-ARE signal pathway involved is necessary to be discussed.Part I The protective effect and mechanism of ischemic postconditioning on the acute lung injury induced by intestinal ischemia-reperfusionObjective:To examine the expression of Nrf2/ARE signal pathway and its downstream substrates on acute lung injury induced by IIR and on the effectiveness of the IPO. Therefore, to elucidate the role and mechanism of Nrf2/ARE signal pathway.Methods:36C57male mice were divided randomly into three groups:control group (group C, n=12), ischemia-reperfusion group (group I/R, n=12), ischemic postconditional group (group IPO, n=12). Pulmonary microvascular permeability and the degree of pulmonary edema were detected to assess the lung function. The sections of lung tissue were taken for light microscopic examination. Either TNF-a, IL-6and IL-10were measured by ELISA. The protein expression of Nrf2and HO-1in the lung tissue were detected by immunohistochemical and Western blotting technique. The levels of MDA and the activity of SOD in lung tissue were also determinated by spectrophotometric method.Results:The degree of lung injury in group I/R was significantly increased, the mean wet/dry weight ratio and permeation index of lung in group I/R were obviously higher than those in group C (all P<0.05). The expression of TNF-α、IL-6in group I/R was also significantly higher than those in group C (P<0.05)while the expression of IL-10in group I/R was lower compared with those in group C (P<0.05). The degree of lung injury was reduced after IPO treatment(P<0.05), The mean wet/dry weight ratio and permeation index of lung in group IPO was significantly lower than those in group I/R as well as the expression of TNF-α and IL-6(P<0.05). The expression of IL-10in group I/R was significantly increased than those in group C (P<0.05). The expression of Nrf2, HO-1in group IPO was significantly increased than those in group I/R and group C (P<0.05). The level of MDA and the activity of SOD of lung tissue in the group IPO was higher than those in group C but it was lower than those in group I/R (all P<0.05)..Conclusion:IPO rhythm stimulation and intervention on intestinal can reduce the acute lung injury induced by ischemia-reperfusion. The protective mechanism is associated with that the expression of inflammatory factor and induces ROS generation was stimulated by the rhythm stimulation and intervention, then they activate Nrf2and promote the HO-1anti-oxidant protein and detoxifying enzymes SOD, finally attenuate acute lung injury induced by intestinal ischemia-reperfusion. Part Ⅱ The protective effect and mechanisms of the ischemic postconditioning on the acute renal injury induced by intestinal ischemia-reperfusionObjective:To investigate the expression of Nrf2/ARE signal pathway and its downstream substrates on acute renal injury induced by IIR and on the effectiveness of the IPO. Therefore, to elucidate the role and mechanism of Nrf2/ARE signal pathway.Methods:36C57male mice were divided randomly into three groups:control group (group C, n=12), ischemia-reperfusion group (group I/R, n=12), ischemic postconditioning (group IPO, n=12). ischemia-reperfusion model of intestinal and ischemic postconditioning model were used, pathological injury of renal were observed by light-microscop, BUN, Cr and NGAL content in serum were also examined,and the levels of TNF-α、IL-6, and IL-10in renal tissue were measured, the protein expression of Nrf2and HO-1in renal tissue were detectedd by immunohistochemical and Western blotting technique, The levels of MDA and the activity of SOD in lung tissue were also determinated by spectrophotometric method.Results:The degree of renal injury in group I/R was increased after45min of ischemia and2hours of reperfusion (P<0.05) as well as of BUN, Cr and NAGL (P<0.05). The expression of Nrf2and HO-1in group I/R was significantly higher than those in group C by immunohistochemical technology and Western blotting analysis (P<0.05). The level of MDA in group I/R were significantly higher than that in group C in renal tissue (P<0.05) while the activity of SOD enzyme was significantly lower than that in group C (P<0.05). After ischemic postconditioning treatment, the degree of renal injury in group IPO was higher than that in group C (P<0.05) but lower than that in group I/R (P<0.05), the serum BUN, Cr and NAGL were significantly reduced in group IPO (P<0.05). The expression of Nrf2and HO-1in group IPO were significantly increased than those in group I/R and group C by immunohistochemical and Western blotting analysis (P<0.05), the level of MDA in group IPO was significantly reduced than that in group I/R (P<0.05) but higher than that in group C (P<0.05), the activity of SOD was significantly higher in group IPO than that in group I/R (P<0.05) but lower than that in group C (P<0.05). There were no difference of TNF-a, IL-6and IL-10expression in every groups (P<0.05).Conclusion:IPO rhythm stimulation and intervention on intestinal system can reduce the renal injury caused by ischemia-reperfusion. Its mechanism is related to that Nrf2was activated by ischemic postconditioning rhythm stimulation and intervention, and then promote HO-1anti-oxidant protein and detoxifying enzymes SOD, so as to reduce the renal injury induced by ischemia-reperfusion. |
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