Effects On Panax Notoginseng Saponins Postconditioning Reducing Rabbits' Hemorrhagic Shock And Resuscitation Myocardial Damage By Mitochondrial Cx43

Objective:To investigate the mechanism of Panax notoginseng saponins postconditioning reducing myocardial damage and mitochondria damage in hemorrhagic shock and resuscitation.Methods:30 healthy adult male New Zealand white rabbits were randomized into sham operation group?SHAM?;hemorrhagic shock and resuscitation group?HSR?;hemorrhagic shock and resuscitation+PNS postconditioning group?HP?;hemorrhagic shock and resuscitation+inhibition18?-Glycyrrhetinic acid?18-AGA?+PNS postconditioning group?HAP?;hemorrhagic shock and resuscitation+inhibition 18?-Glycyrrhetinic acid group?HA?;hemorrhagic shock and resuscitation model was induced by withdrawing blood?35%?40%of the total blood volume?from the right common carotid artery over an interval in 15 min,the blood was stored in sterile pre-heparinized bags,and 1 h later the animals were resuscitated with infusion of the shed blood via the right femoral vein,in group SHAM,animals were given the trachea intubation and arteriovenous catheterization only;in group HP,100mg/kg PNS was injected when hemorrhagic was stable for45min;in group HAP,75mg/kg 18-AGA was given intraperitoneally before withdrawing blood,and 100mg/kg PNS was injected when hemorrhagic was stable for 45min;in group HA,75mg/kg 18-AGA was given intraperitoneally before hemorrhagic shock and resuscitation.Mean arterial pressure?MAP?was recorded on resting-state?T₀?,30min after hemorrhagic shock?T₁?,1h after hemorrhagic shock?T₂?,30min after resuscitation?T₃?,1h after resuscitation?T₄?.The animals were rapidly sacrificed at T₄.myocardial tissue in the left ventricle was for transmission electron microscopy to observe the ultrastructure of mitochondria.Mitochondria were isolated and extracted from the myocardium of the left ventricle for subsequent detection of the expression of mitochondrial Cx43.The heart apex tissue was prepared for TUNEL detection of apoptosis.Results:1. MAP results showed that:Compared with group SHAM,MAP in group HSR,HP,HAP and HA decreased in T_1-4 period?P<0.05?.Compared with group HSR,HAP and HA,MAP increased in the group HP at T₂,with statistically significant difference?P<0.05?.2. Tunel results show that compared with the group SHAM,myocardial cell apoptosis rate of group HSR,HP,HAP and HA increased?P<0.05?.Compared with group HSR,myocardial apoptosis rate of group HP decreased?P<0.05?;Compared with group HAP and HA,myocardial cell apoptosis rate of the group HP decreased?P<0.05?.3. Western blot results showed that compared with group SHAM,the expression of mitochondrial Cx43 in group HSR,HAP and HA was down-regulated?P<0.05?.Compared with the group HSR,the expression of mitochondrial Cx43 in the group HP was up-regulated?P<0.05?;however the expression of mitochondrial Cx43 in group HAP and HA was down-regulated?P<0.05?.Compared with the group HP,the expression of mitochondrial Cx43 in group HAP and HA was down-regulated?P<0.05?.4. Ultrastructure results of myocardial mitochondria showed that:in the group SHAM,the myocardial mitochondria were round or oval,the mitochondrial membrane was complete and smooth,the cristae were clear,and the myocardial fibers were neat.In the group HSR,mitochondria were extensively clustered and ruptured,the matrix precipitated and even presented vacuol-like changes,membrane integrity was severely damaged,cristae were unclear,myocardial fiber was broken and dissolved,and mitochondrial integrity was lost.Compared with the group HSR,the myocardial mitochondria in the group HP was significantly improved.The mitochondria were slightly swollen but relatively intact,with clear cristae.The myocardial fibers were arranged in a regular manner,and no serious myocardial fiber dissolution was observed.In the group HAP,mitochondrial swelling was obvious,particles disappeared,cristae were not clear,and integrity was obviously damaged.In the group HA,mitochondrial integrity was seriously damaged,with matrix precipitation,most of the crista broken,myocardial fiber broken and dissolved,and mitochondrial integrity lost.According to Flameng scores,mitochondrial ultrastructure scores were performed,and the results showed that group HSR,HP,HAP and HA had higher mitochondrial ultrastructure scores than group SHAM?P<0.05?.Compared with group HSR,the mitochondrial ultrastructure score of group HP and HAP were decreased?P<0.05?.Compared with group HA,the mitochondrial ultrastructure scores of group HP and HAP were decreased?P<0.05?.Conclusions:PNS postconditioning reduces the myocardial damage in hemorrhagic shock and resuscitation through up-regulating the expression of mitochondrial Cx43.