| Objective:To investigate the effect of resveratrol on gluconeogenesis pathway and its regulatory mechanism in exercise-induced fatigue rats.Methods:The weight-bearing swimming training was used to simulate long and intense exercise.Male Sprague Dawley rats aged 6-8 weeks were randomly divided into 4 groups:blank control group(C),resveratrol group(R),exercise group(E),and resveratrol+exercise group(RE),with 12 rats in each group.Groups E and RE swam at 5%weight for 1 hour per day,6 days per week for 6 weeks.Groups R and RE were gavaged with 50 mg/kg resveratrol solution,and groups C and E were gavaged with equal volume of dimethyl sulfoxide solution.The drug was administered by gavage 1 hour after exercise,once a day for 6 weeks.24 hours after the end of the experiment,the plasma BUN and CK levels were detected to measure the degree of fatigue.Blood glucose,liver glycogen,lactate and pyruvate were measured to measure hepatic gluconeogenesis.PEPCK and G6Pase activities were detected by the kit.The mRNA expression levels of SIRT1,CREB and PGC-1α in liver tissue were detected by RT-PCR.Results:(1)After six weeks of intervention,exercise × resveratrol two-factor ANOVA was performed on plasma BUN and CK levels of rats,and there was a significant interaction effect on BUN levels(P<0.05).Simple effect analysis showed that plasma BUN content in group E was significantly higher than that in group C(P<0.05).The plasma BUN content in RE group was significantly lower than that in E group(P<0.01).There was no significant interaction effect on CK level(P>0.05).Independent sample T-test analysis showed that plasma CK content in group E was significantly higher than that in group C(P<0.05),and plasma CK content in group RE was significantly lower than that in group E(P<0.05).(2)After six weeks of intervention,exercise × resveratrol two-factor ANOVA was performed on blood glucose and liver glycogen levels of rats,and there was no significant interaction effect on blood glucose levels(P>0.05).Independent sample Ttest analysis showed that plasma blood glucose level in group E was significantly lower than that in group C(P<0.01).The blood glucose level in RE group was significantly higher than that in E group(P<0.05).There was a significant interaction effect on the level of liver glycogen(P<0.05).Simple effect analysis showed that the content of liver glycogen in group E was significantly lower than that in group C(P<0.01),and the content of liver glycogen in group RE was significantly higher that in group E(P<0.01).After six weeks of intervention,the lactic acid content,pyruvate content and lactic acid/pyruvate ratio in the liver of rats were analyzed by two-factor ANOVA of exercise× resveratrol,and there were significant interaction effects among the three levels(P<0.05).Simple effect analysis showed that,the contents of lactic acid and pyruvate and the ratio of lactic acid to pyruvate in liver of rats in group E were significantly higher than those in group C(P<0.01,P<0.01,P<0.01),and the contents of lactic acid and pyruvate and the ratio of lactic acid to pyruvate in liver of rats in group RE were significantly lower than those in group E(P<0.01,P<0.05,P<0.01).(3)After six weeks of intervention,the contents of PEPCK and G6Pase in the liver of rats were analyzed by the two-factor ANOVA analysis of exercise × resveratrol,and there was a significant interaction effect on PEPCK content(P<0.05).Simple effect analysis showed that the content of PEPCK in the liver of rats in group E was significantly lower than that in group C(P<0.01).The content of PEPCK in liver of rats in RE group was significantly higher than that in E group(P<0.01).There was no significant interaction effect on G6Pase content(P>0.05).Independent sample T-test analysis showed that the content of gluconic rate-limiting enzyme G6Pase in group E was significantly lower than that in group C(P<0.05),and the content of G6Pase in group RE was higher than that in group E,but there was no significant difference(P>0.05).(4)After six weeks of intervention,the mRNA levels of SIRT1,CREB and PGC-1α in rat liver were analyzed by exercise × resveratrol two-factor ANOVA,and there was no significant interaction effect between SIRT1 and CREB mRNA levels(P>0.05).Independent sample T-test analysis showed that,the mRNA of SIRT1 in liver of group R was significantly higher than that of group C(P<0.01),the mRNA of SIRT1 and CREB in liver of group E was significantly lower than that of group C(P<0.01),and the mRNA of SIRT1 and CREB in liver of group RE was significantly higher than that of group E(P<0.01).There was a significant interaction effect on the mRNA of PGC1α(P<0.05).The simple effect analysis showed that the mRNA level of PGC-1α in liver of group E was significantly lower than that of group C(P<0.01),and the mRNA level of PGC-1α in liver of group RE was significantly higher than that of group E(P<0.01).Conclusion:Resveratrol has an improvement effect on exercise fatigue caused by long-term and intense exercise,and its mechanism may be related to the regulation of SIRT1/CREB/PGC-1α pathway,the improvement of PEPCK activity,the promotion of hepatic gluconeogenesis,and the increase of blood glucose and hepatic glycogen levels. |
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