| Hemorrhagic shock inducing multiple organ dysfunction syndrome and even the subsequent multiple organ failure has been one of the main reasons for patient death in critical conditions. A great number of studies indicate that blocking the return of lymph to circulation may alleviate organ inflammation, free radical injury and energy metabolism dysfunction. Aquaporins (AQPs) widely distribute on the cell membrane of different tissues and involve in maintaining of fluid equilibrium in the body by regulating secretion, transport and absorption of water. The dysfunction of AQPs may result in the disturbance of water metabolism, such as edema, and then promote the occurrence and development of the disease. However, it is not known whether the mechanism that the organ protective effects caused by the blocking return of mesenteric lymph to systemic circulation is related to exert influence over AQPs.To explore the role of AQPs in organ injury mediated by shock mesenteric lymph, the present study observed the effects of the mesenteric lymph drainage on the water and AQPs contents in lung, liver, kidney and myocardium. In consideration of experimental evidences that the expression of AQPs modulated by steroid hormones and nitric oxide (NO), the further experiment tested the levels of testosterone and estradiol in plasma, the contents of NO, cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in different tissues for the determination of AQPs modulating the organ function and fluid equilibrium during hemorrhagic shock.Eighteen male Wistar rats were randomized to sham, shock, shock plus mesenteric lymph drainage (shock+drainage) groups with each6 cases. The operation was performed on femoral region after all the animals were anesthetized with pentobarbital. The right femoral vein was separated and cannulated for anticoagulation with heparin sodium. A minimally heparinized polyethylene catheter was introduced into the right femoral artery used to continuously monitor the animals’mean artery pressure (MAP) throughout the experiment. Another catheter was inserted into the left femoral artery for bleeding by a syringe pump. A laparotomy was carried out to separate the mesenteric lymph duct from surrounding connective tissues. After a30-min stabilization period, blood was withdrawn from the right femoral artery to a MAP of40mmHg within10min at an even speed and was maintained at this level by withdrawing or reperfusion shed blood as needed, thus, the hemorrhagic shock model was established in shock and shock+drainage groups. After90min of hypotension, the ejective blood and the equal volume of Ringer’s solution were reperfused in30min through right femoral vein, the MAP was observed to3h after infusion end. In the shock+drainage group, after infusion finished, the mesenteric lymph duct was cannulated and mesenteric lymph was drained up to3hours after shock. In the sham group, the rats were anesthetized, cannulated and operated as described above, but no blood was withdrawn or infused. The specimens of blood, lung, liver, kidney and myocardium were harvested at3h of hypotension in rats of shock and shock plus drainage group and at corresponding time point in sham group for the next experiments. The levels of testosterone and estradiol in plasma were measured using chemiluminescence immune assay. Part of the animal specimens was used to determine the water contents and part of the animal specimens was prepared10%(V/V) tissue homogenate for examination of NO, cAMP, cGMP and AQP1.Results showed that the water content in lung of shock group was increased significantly when compared with that of sham group, PSML drainage reduced the water content in lung. There were no statistical differences in water contents in hepatic, renal and mycardial tissue among the sham, shock and shock+drainage groups. Results also showed that the AQP1contents in pulmonary, hepatic, renal and mycardial tissue of shock group were increased significantly than those of sham group; however, PSML drainage reduced these increased indices, meanwhile, these indices were still increased than those in sham group except for renal tissue.Furthermore, the results showed that there was no difference in estradiol levels in plasma between shock group and sham group; however, the estradiol levels in shock+drainage group were lower than those in sham and shock groups.At the same time, the content of testosterone in plasma in shock group was significantly decreased than that of sham group, which in shock+drainage group was no significant difference with sham and shock groups. Further research found that the contents of NO, cAMP in lung, liver, kidney and myocardium and cGMP in lung, liver and myocardium in shock group were increased significantly when compared with those of sham group; whereas PSML drainage decreased the contents of NO in lung, liver, kidney and myocardium and cAMP, cGMP in lung, liver and myocardium, and there was no significantly effects on cAMP, cGMP in kidney.In summary, the AQP1levels in lung, liver, kidney and myocardium were increased in hemorrhagic shock rats following fluid resuscitation, mesenteric lymph drainage attenuated the AQP1contents. Its mechanism was related to cAMP and cGMP regulated by NO. AQP1plays a certain role on mesenteric lymph drainage alleviating multiple organ injury.The present findings enrich the theroy of multiple organ injury following hemorrhagic shock, and provide an experimental evidence for targeting the return of mesenteric lymph to prevent and treat multiple organ injury. |
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