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Exogenous Hydrogen Sulfide Inhibits Inflammation and Apoptosis in Rats Induced by Hemorrhagic Traumatic Shock

Author: GaoCao
Tutor: ChaiWei; GaoChangJun
School: Fourth Military Medical University
Course: Anesthesiology
Keywords: Hemorrhagic traumatic shock Exogenous hydrogen sulfide Cardio-protection Inflammation Apoptosis
CLC: R459.7
Type: Master's thesis
Year: 2012
Downloads: 98
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Hemorrhagic traumatic shock (HTS) is one of the leading death causes incivilian and military trauma. HTS is a type of acute circulatory insufficiencycaused by severe trauma through the neurovascular reflex. Characterizedmicrocirculatory disturbance during HTS can finally lead to severe ischemia,hypoxia and multiple organs dysfunction syndromes (MODS). In considerationof these factors, methods to attenuate ischemia-reperfusion injury, decreaseoxygen consumption and inhibit inflammation response may provide newstrategies for improve the prognosis.Hydrogen Sulfide (H2S) is a newly accepted gaseous signaling moleculeafter NO and CO. Studies showed H2S is extensively involved in manypathophysiological processes of the cardiovascular system, inflammatoryreactions, oxidative stress and cell metabolism. Studies found H2S hadsignificant inhibitory effect on metabolism, increased oxygen supply, improved cell survival and prevented irreversible injury. It has been reported thathemorrhage can activate myocardial NF-κB. Ganster and colleagues found thatH2S can inhibit the expression of NF-κB. Exogenous H2S can significantlydecrease the infarct area in a rat coronary artery ligation model, reduce theseverity of ischemia/reperfusion-induced arrhythmias and attenuate apoptosisand autophagy in the setting of cardioplegia and cardiopulmonary bypass.Our previous study found that H2S can protect against damage caused byhemorrhagic traumatic shock on lung and inhibit inflammatory cytokinescascade. The present study is designed to investigate the cardio-protectiveeffects of exogenous hydrogen sulfide in rats with hemorrhagic traumatic shockand to explore the possible mechanism of inhibiting inflammation and apoptosisto provide a new strategy for the clinical situation.Object:By using the model of hemorrhagic traumatic shock, the present study wasdesigned to investigate the cardio-protective effects of exogenous hydrogensulfide in rats with hemorrhagic traumatic shock and to explore the possiblemechanism and provide a new way for the clinical treatment.Methods:1. Forty male SD rats, weighing250~300g, were divided into4groupsrandomly as follows:(1) Sham group (n=10);(2) Sham+NaHS group (n=10);(3) Hemorrhagic traumatic shock (HTS) group (n=10);(4) Hemorrhagictraumatic shock+NaHS (HTS+NaHS) group (n=10). The hemorrhagictraumatic shock model is replicated in this study. Sham group underwent thewhole surgical procedures without hemorrhage and resuscitation. Sham+NaHS group underwent the whole procedures as the sham-operatedgroup, except that28μmol/kg NaHS was administered intraperitoneally atthe same time point of resuscitation. HTS group underwent the wholesurgical procedures. HTS+NaHS group underwent the whole procedureswith intraperitoneal injection treatment of28μmol/kg NaHS10min beforeresuscitation.2. Mean artery pressure (MAP) was monitored during the procedure.3. Blood samples were taken at different time point to detect CK, LDH, TNF-α,and IL-6levels.4. Morphological changes of heart were observed by hematoxylin and eosin(HE) staining at4h after resuscitation among every group.5. Ultrastructural damages were observed by transmission electron microscopyat4h after resuscitation among each group.6. Expressions of IKK/IκB/NF-κB and HMGB1were detected by Western-blot.7. Expressions of Survivin, Caspase-3and Bax were detected by Western-blot.Result:1. Compared with Sham group and Sham+NaHS group, MAP decreaseddramatically in HTS group and HTS+NaHS group (P<0.05).Compared withHTS group, MAP elevated in HTS+NaHS group (P<0.05).2. Compared with Sham group and Sham+NaHS group, serum concentrationsof CK and LDH elevated significantly in HTS group and HTS+NaHS group(P<0.05). Compared with HTS group, administration of NaHS effectivelydecreased the elevation of CK and LDH in HTS+NaHS group (P<0.05).3. Compared with Sham group and Sham+NaHS group, TNF-α and IL-6levels increased in HTS group and HTS+NaHS group (P<0.05). Compared withHTS group, administration of NaHS effectively decreased TNF-α and IL-6in HTS+NaHS group (P<0.05).4. HE staining showed well-lined cardiocytes, uniformly-dyeing of cardiacmuscle fibres, and normally-distributed cardiac muscle spaces in rat heartsof Sham group and Sham+NaHS group. HTS resulted in edema ofmyocardial cells, ununiformly-dyeing of cardiac muscle fibres, andabnormally-distributed cardiac muscle spaces. Administration of NaHSattenuated those changes induced by HTS mentioned above.5. Under transmission electron microscope, orderly ranged cardiac sarcomeres,clearly composed cardiac stripes, completely structured mitochondria wereobserved in the cardiac tissue of Sham group and Sham+NaHS group.Irregularly-ranged cardiac sarcomeres, ill-defined cardiac stripes, swollenmitochondria with disorganized fractured cristae, dilated sarcoplasmicreticula were observed in the cardiac tissue of HTS group. In theHTS+NaHS group, the sarcoplasmic reticula were not significantly dilated,the structure of mitochondria was relatively clear and complete comparedwith HTS group.6. Compared with Sham group and Sham+NaHS group, expression ofphosphorylated IKK and phosphorylated IκB increased in HTS group andHTS+NaHS group (P<0.05). Compared with HTS group, expression ofphosphorylated IKK and phosphorylated IκB decreased in HTS+NaHSgroup (P<0.05).7. The expression of NF-κB was not altered in HTS group and HTS+NaHSgroup, and the expression of phosphated NF-κB increased in HTS group andHTS+NaHS group (P<0.05). Compared with HTS group, expression of phosphorylated NF-κB decreased in HTS+NaHS group (P<0.05).8. The expression of total protein of heart tissue did not change each group, butthe level of HMGB1in cytoplasmic protein of heart tissue increased in HTSgroup and HTS+NaHS group (P<0.05). Compared with HTS group,expression of HMGB1in cytoplasmic protein of heart tissue decreased inHTS+NaHS group (P<0.05).9. Compared with Sham group and Sham+NaSH group, expression of Survivindecreased in HTS group and HTS+NaHS group (P<0.05). Compared withHTS group, administration of NaHS effectively increased Survivin level inHTS+NaHS group (P<0.05).10. Compared with Sham group and Sham+NaSH group, expression ofCaspase-3and Bax increased in HTS group and HTS+NaHS group(P<0.05).Compared with HTS group, administration of NaHS effectivelydecreased Caspase-3and Bax expressionin HTS+NaHS group (P<0.05).Conclusion:1. Exogenous hydrogen sulfide improved MAP and attenuated cardiac injuryinduced by HTS.2. Exogenous hydrogen sulfide inhibited the IKK/IκB/NF-κB signal pathwayand inflammation.3. Exogenous hydrogen sulfide increased the expression of Survivin anddecreased the expression of Caspase-3and Bax.

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