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Effect Of Recombinant Human Growth Hormone On The Functions And Apoptosis Of PMNs In Rats With Gut Ischemia-reperfusion

Posted on:2004-06-17Degree:MasterType:Thesis
Country:ChinaCandidate:W B QieFull Text:PDF
GTID:2144360092499184Subject:Anesthesia
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Objectives To observe the changes of the functions and apoptosis of polymorphonuclear neutrophils(PMNs) in blood, lipid peroxides(LPO) and lactate levels in plasma, and myeloperoxidase(MPO) activity and PMNs pathological morphology in intestinal tissue, to investigate the effects of recombinant human growth hormone(rhGH) on PMN's functions and apoptosis, the expression of apoptosis-associated gene, and to probe into its possible mechanisms in preventing PMN-mediated injury and gut-origin inflammatory response in rats with gut ischemia-reperfusion(GIR) injury.Methods GER injury model was replicated by clipping superior mesenteric artery for 60minutes. Sixty Wistar rats were randomly divided into 3 groups: sham-controlled group(Group S), GIR group(Group G) and rhGH group(Group R). Group R was subdivided into Group Rat, and Group Ri2h according to different time of the administration of rhGH. Blood samples were collected at 24, 48 and 72 hours after reperfusion of gut blood flow in rats. PMNs were separated from blood for detecting its functions and apoptosis, phagocytic rate and phagocytic index, and Fas expression on them. Plasma was harvested for the determination of plasma lipid peroxides and lactic acid. Intestinal tissues were collected for the pathological morphology and the MPO assay.ResultsIncreased Apoptosis of PMNs shown in rats with gut ischemia-reperfusioninjury. For example, lessened bulk, condensation of both the cytoplasm and the nuleus, condensed and lobulated chromatin and the formation of apoptotic body in PMNs were observed by electron transmission microscope and light microscope.The apoptotic rate of PMNs in Group G was higher than that in Group S and reached to the peak 72h after reperfusion. Compared with Group G, the significantly decreased apoptotic rate of PMNs showed in either Group Rsh or Group Ri2h- However, no statistical difference was found between them. The apoptotic rate was positively correlated remarkably with PMNs of Fas gene positive expression, LPO levels in plasma and activity of NADPH oxidaseCr^ 0.9170, P<0.001: r=0.5380, P<0.001; r=03110, P<0.05).The PMNs of Fas gene positive expression in Group G was more than that in Group S, and reached to the peak 48 hours after reperfusion. The administration of rhGH(both Group Rsh and Group Ri2h) decreased evidently the Fas gene positive expression of PMNs in rats with GIR-induced injury. However, no statistically difference was found between them. The PMNs of Fas gene positive expression was positively correlated significantly with LPO levels inplasma(r=0.5470, P<0.001).The NADPH oxidase activity of PMNs in Group G was higher than that in Group S(P<0.01), and reached to the peak at 24h after reperfusion. The administration of rhGH evidently inhibited the increased NADPH oxidase activity of PMNs in rats with GIR injury. There was no statistical difference between Group R}h and Group R^h- The changes of NADPH oxidase activity of PMNs was correlated with the phagocytic rate and phagocytic index of PMNs(r = 0.6120, P<0.001; r=0.5880, P<0.001).The phagocytic rate of PMNs in Group G was higher than that in Group S. Statistically significant difference was found 24h and 48h after reperfusion between them(P<0.05). The administration of rhGH might decrease the phagocytic rate of PMNs in rats with GIR injury. There was no statistically significant difference between Group R3h and Group R12h. The phagocytic indexof PMNs in Group G was also higher than that in Group S. Statistically significant difference was found 24h and 48h after reperfusion between Group G and Group S(P<0.05). The administration of rhGH might decrease the phagocytic index of PMNs in rats with GIR injury. There was no statistically significant difference between Group RSI, and Group RIIH-The levels of LPO in plasma in Group G was evidently higher than that in Group S and was the highest 24h after reperfusion, which was significantly cut down by the administration of rhGH, but higher than that in Group S. There was no statistically significant...
Keywords/Search Tags:ischemia/reperfusion injury, recombined human growth hormone, polymorphonuclear neutrophils, apoptosis, respiratory, burst oxygen free radicals
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