Protective Effect Of Coenzyme Q10 On Rats With Simulated Rapid Entry Into High Altitude And Severe Hemorrhage

Plateaus in China account for about 1/6 of the total land area.The terrain along the southwest border is mostly plateaus and mountains,and the altitude is generally above4000m.Acute exposure to low-pressure and low-oxygen environments on the plateau will cause a series of pathophysiological changes in the human body,significantly reduce physical strength and endurance,and severely impede military operations.In case of an armed conflict,severe blood loss will result,which will pose more of a threat to the lives and health of combatants.Thus two problems will arise:（1）How to improve the stamina of personnel engaged in plateau operations?（2）How to reduce organ damage and life hazards after severe blood loss?Coenzyme Q10（CoQ10）is a small molecule targeted by mitochondria,the main role of which is to participate in the electron transport chain in mitochondria to promote the generation of ATP.It also has antioxidant and anti-inflammatory properties,which can improve mitochondrial oxidative stress damage under hypoxic conditions by regulating mitochondrial function.There have been no detailed reports on the effects of CoQ10 on rapid entry into the plateau and severe blood loss.Therefore,this study was intended to explore the protective effect of CoQ10 on simulated rapid entry into the plateau and severe blood loss in rats.Objective:To explore the effect of coenzyme Q10 on simulated rapid entry into the plateau and severe blood loss in rats.Methods:1.The effect of CoQ10 on simulated rats rushing into the plateauThirty-six male Wistar rats aged 6 to 8 weeks were randomly divided into the normal-pressure and normal-oxygen group（NG）,low-pressure hypoxic group（HG）,and the low-pressure hypoxic CoQ10 group（CoQ10）,with 12 rats in each group.The COQ10 group was given 30mg/kg CoQ10 once a day,while NG and HG groups received 0.5%sodium carboxymethyl cellulose（CoQ10 solvent）daily.After 4d,the HG and COq10 groups moved back to the hypoxic chamber to simulate a rush into the6000m plateau for 48h.All the rats in the three groups were given the drug intragastrically for 2 days according to the previous dose.One after the last administration,six of the rats in each group were sacrificed to take their abdominal aorta blood for detection of blood gas indexes.The serum was preserved to detect oxidative stress indexes and renal function indexes.The kidney tissue was preserved to detect oxidative stress indexes.HE staining was used to observe pathological injury to the heart,lung,kidney and brain tissue,TUNEL kit was used to detect apoptosis and calculate positive tissue apoptosis rates.The other six rats in each group were tested for exhaustion.2.Effects of CoQ10 on rats with severe blood lossThis part of the experiment was divided into three batches,with 4 h,8 h,and 24 h as the experimental endpoints.Male Wistar rats aged 6 to 8 weeks were divided into three groups in each batch:severe bleeding CoQ10 group（CoQ10 group）,severe bleeding control group（Ctrl group）,and sham group（sham group）,with 6 rats in each group.The co Q10 group was given 30mg/kg CoQ10 by intragastric administration for 7days,while the Ctrl group and the sham group were given 0.5%CMC by intragastric administration for 7 days.A rat model of severe blood loss was established as follows.After anesthesia induced by isoflurane,the rats were kept anesthetized by continuous low-flow inhalation of isoflurane.The distal end of the right femoral vein was ligated and fixed with a catheter inserted into the proximal end for heparin anticoagulation.The distal end of the right femoral artery ligated,and fixed with a catheter connected to the injection pump for hemorrhage.The distal end of the left femoral artery was lapped,and the proximal end of the femoral artery was lapped and fixed with a catheter.The MP150multifunctional physiological recorder was used to detect the mean arterial pressure,heart rate,core body temperature,and other important physiological indicators.Hemorrhage lasted for one hour,and 25%of the uniform-speed hemorrhage occurred in the first 20 minutes and another 25%in the last 40 minutes.The survival time of rats was counted.At the experimental endpoints（4h,8h,24h）,the heart,lung,kidney,brain,and other important tissues were taken for HE staining to observe histopathologic changes,and the arterial blood was taken for centrifugation and the preserved serum was detected for oxidative stress.The kidney tissues were preserved to detect oxidative stress indexes.Results:1.Compared with the NG group,the swimming exhaustion time of rats in the HG group was significantly shortened（P<0.01）.Arterial blood gas p H,arterial oxygen partial pressure（PO₂）,arterial oxygen saturation（SO₂）and arterial bicarbonate（HCO₃^-）were significantly decreased,while arterial carbon dioxide（PCO₂）,alkali residual（BE）,serum calcium ion(Ca²⁺)and arterial lactate content（Lac）were significantly increased（P<0.01）.Pathological staining revealed pulmonary interstitial edema,cerebral edema,renal tubule epithelial cell edema,and myocardial injury.TUNEL staining showed increased apoptosis of renal tubular epithelial cells.The apoptosis rate of renal tubular epithelial cells was significantly increased（P<0.01）,so was the serum malondialdehyde（MDA）level,but the total superoxide dismutase（T-SOD）level was significantly decreased（P<0.01）.The level of BUN and CRE were significantly increased（P<0.01）,so was the MDA level in kidney tissues,but the T-SOD level in kidney tissues was significantly decreased（P<0.01）.Compared with HG rats,the swimming exhaustion time of rats in the CoQ10 group was significantly prolonged（P<0.05）,arterial blood gas p H was significantly increased,while PCO₂,Na⁺,Ca²⁺,and Lac were significantly decreased（all P<0.05）.In the CoQ10 group,pulmonary edema,cerebral edema,and tubular epithelial cell edema were significantly improved.The apoptosis rate of renal tubular epithelial cells in the CoQ10 group was significantly decreased（P<0.05）.The serum MDA level in the CoQ10 group was significantly decreased.The serum T-SOD level in the CoQ10 group was significantly increased（P<0.05）.The serum CRE level and BUN level of rats in the CoQ10 group were significantly decreased（P<0.05）,so was the level of MDA in kidney tissues,but the level of T-SOD in kidney tissues was significantly increased.2.There was no statistically significant difference in survival between the two groups.There was no significant difference in mean arterial pressure,core body temperature,and heart rate between the three groups of rats during hemorrhage（P>0.05）.Compared with the sham group,slight pathological changes were observed in the heart,lung,and brain of rats in the other two groups after hemorrhage,and no significant differences were observed in histopathology 4h,8h,and 24h after hemorrhage.The renal tubule cells of the Ctrl group showed obvious edema after 4h of hemorrhage,which returned to normal after 24h,while the renal pathology of the CoQ10 group showed no significant changes at different time points.There was no statistically significant difference in serum MDA and T-SOD level between the three groups of rats after 4h of hemorrhage（P>0.05）.There was no statistically significant difference in the level of MDA and T-SOD in kidney tissues between the three groups of rats after 4h of hemorrhage（P>0.05）.Conclusion:On the one hand,CoQ10 can alleviate the oxidative stress of rat tissues in the simulated plateau environment,relieve the pathological injury of rats,and improve the anti-fatigue ability of rats.On the other hand,it can alleviate the early renal pathological damage,thereby alleviating the injury of severe hemorrhage to rats,but it has no obvious effect on its survival rate.