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Effect Of Hypertonic Saline Resuscitation On HO-1 MRNA Expression And Apoptosis Of Visceral Organs In Rats With Hemorrhagic Shock

Posted on:2010-10-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Q LuFull Text:PDF
GTID:1114360275977214Subject:Emergency Medicine
Abstract/Summary:PDF Full Text Request
Background:Hemorrhagic shock accounts for a large portion of civilian and military traumadeaths. It's physiopathologic characteristic is failure of the microcirculatory system thatresults in inadequate tissue perfusion with subsequent ischemia, cellular hypoxia, andorgan dysfunction. Consequently, the study of hemorrhagic shock remains a focal issuein traumatology.At present, hypertonic saline (HTS) has been applied as alternative resuscitationstrategies in patients of hemorrhagic shock. HTS solutions usually consist of 7.5%NaCl. A number of recent studies disclosed previously unsuspected properties of HTSresuscitation, amongst them the correction of endothelial and red cell edemaaccompanying significant consequences in capillary blood flow. Furthermore, HTSresuscitation may have favorable immunomodulatory effects and alleviateischemia-reperfusion injury of organs.Heme oxygenase-1 (HO-1), a stress-inducible protein, is an important cytoprotective agent against oxidative stress and ischemia/reperfusion (I/R) injury.Our study used a model of rat with severe hemorrhagic shock to test the effects ofdifferent crystalloid solutions on HO-1 mRNA expression and apoptosis of visceralorgans, and evaluated the resuscitative value and mechanism of action of hypertonicsaline resuscitation on the molecular biologic level.Methods:A model of rat with severe hemorrhagic shock was established in 21 SDrats. According to different crystalloid solutions administered in the "pre-hospitalphase", the rats were randomly divided into Sham group (only underwent anesthesiaand cannulation without shock or resuscitation), normal saline resuscitation group (NSgroup), and hypertonic saline resuscitation group (HTS group). Each group contained7 rats. The HO-1 mRNA expression and apoptosis in heart, liver, lung, kidney andsmall intestinal mucosa of rats after hemorrhage and resuscitation were detected bySYBR Green I fluorescence quantitative reverse transcriptase-polymerase chainreaction, FITC-Annexin V/PI double staining method and flow cytometry. The curativeeffects were compared and analysed statistically.Results:1,In this model of rat with severe hemorrhagic shock, after receiving a solution ofeither normal saline or hypertonic saline, rats of NS and HTS groups rapidly showedsimilar trends toward restoration of hemodynamic parameters and stably sustained meanarterial pressure (MAP) thereafter.2,There was increased apoptosis of visceral organs in rats of NS and HS groupsafter hemorrhagic shock and resuscitation, especially in the lung and small intestinalmucosa. The apoptotic rates of heart, liver, lung, kidney and small intestinal mucosa were obviously higher in NS group than those in Sham group, and the comparisonshowed statistically significant difference (P<0.01 or P<0.05). Compared with Shamgroup, the higher apoptotic rates of lung and small intestinal mucosa of HTS groupshowed statistically significant difference (P<0.01). In addition, the apoptotic ratesof heart, lung, and small intestinal mucosa were obviously higher in NS group thanthose in HTS group (P all<0.01).3,The HO-1 mRNA expressions of visceral organ cells were induced byhemorrhagic shock and resuscitation, but were further increased with HTS. The HO-1mRNA expressions of liver and kidney cells were higher in HTS group than those inSham group, and the comparison showed statistically significant difference (P all=0.013).4,There was significant negative correlation between HO-1 mRNA expression andapoptosis of lung and small intestinal mucosa in rats of NS and HS groups afterhemorrhagic shock and resuscitation.Conclusion:In this model of rat with severe hemorrhagic shock, small volume resuscitation withHTS is more effective than NS in reducing the apoptosis and increasing the HO-1mRNA expression of visceral organs of rats with severe hemorrhagic shock, and mayrepresent a novel mechanism, by which HTS resuscitation imparts protection to theorgans and benefits improvement of prognosis.
Keywords/Search Tags:Hypertonic saline solution, Resuscitation, Hemorrhagic shock, Apoptosis, Heme oxygenase-1, Gene expression
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