| Objective: to investigate the acute toxicity of compound multi-dimensional coenzyme Q10 effervescent tablets and its anti-fatigue effect and molecular mechanism in mice by establishing an animal model of exercise training,the purpose of this study was to provide experimental basis for preventing and treating exercise-induced fatigue with compound multi-dimensional coenzyme Q10 effervescent tablets.Methods: the first part: the acute toxicity experiment of compound multi-dimensional coenzyme Q10 effervescent tablets,10 KM mice,half male and half female,were used in the pre-experiment.They were randomly divided into three groups,three in each group,and were treated with 10mg/kg,100mg/kg and 1000MG/kg,respectively,according to the maximum allowed volume(0.4 ml/10G),the mice were given intragastrically.The symptoms and the death number of the mice were recorded and observed for 14 days.According to the death of mice,the simplified dose design was improved and the official test dose was selected.10 KM mice(weight 22 ± 2 g),half male and half female,were given orally for 14 days.The response and death number of mice were recorded and LD50 was determined.The second part: the anti-fatigue experiment of compound multi-dimensional coenzyme Q10 effervescent tablets,60 KM mice were randomly divided into 5 groups,12 mice in each group,Group C,low dose of compound multi-dimensional coenzyme Q10 effervescent tablets(Group L),middle dose of compound multi-dimensional coenzyme Q10 effervescent tablets(Group M),high dose of compound multi-dimensional coenzyme Q10 effervescent tablets(Group H),creatine positive control group(Group P),continuous administration,once a day,Gavage in the morning and weight-bearing swimming in the afternoon.The weight-bearing swimming training was performed from week 2 to Week 6(swimming adaptation training was performed in the first week)for 6days per week,and the weight was gradually increased from 1% to 10% of the body weight at the time of each training until the mice stopped loading at exhaustion.Daily weight measurement,corresponding to the increase or decrease in load.The related indexes were measured in turn,and the time of swimming experiment,climbing pole experiment,forelimb grip force experiment and rotating rod experiment were observed,the levels of LA,Bun,MDA,SOD in serum and LG in liver were detected by chemical colorimetry,and the pathological changes of gastrocnemius muscle were evaluated by HE staining The expressions of AMPK and PGC-1α genes were detected by real-time PCR,and the expression levels of Bcl-2,Bax,AMPK,P-AMPK,PGC-1α proteins were detected by Western blot.Results:(1)After acute toxicity test,LD50 was calculated to be 137.825 mg/kg by the death of mice,the low,middle and high dosages of compound multi-dimensional coenzyme Q10 effervescent tablets were determined.(2)Compared with Group C,the time of weight-bearing swimming was significantly increased in group L(p < 0.01).Compared with L Group,the time of swimming in H group was significantly longer(p < 0.05),the time of climbing the pole was significantly longer(p < 0.01),and the time of turning the stick was significantly longer(p < 0.01).The handgrip strength of forelimbs in L,M,H and P groups was significantly increased(p< 0.01).(3)Compared with Group C,the contents of LA and Bun in group L,M,H and P decreased significantly(p < 0.01).Compared with L Group,there was significant difference in BUN content in P group(p < 0.01).Compared with M Group,there was significant difference in BUN content in P group(p < 0.05).Compared with H group,the content of BUN in P Group was significantly different(p < 0.05),the content of LG in L,M and H groups was significantly increased,and the content of LG in P Group was significantly increased(p < 0.01 or P < 0.05).Compared with L group,the content of LG in H group was significantly different,and the content of LG in P Group was significantly different(p < 0.01).Compared with M group,the content of LG in H group was significantly different,and that in P group was significantly different(p < 0.01).(4)Compared with C group,the content of MDA in L group was significantly decreased(p < 0.05).Compared with L Group,the content of MDA in M and H group was significantly different(p < 0.01),and the content of SOD in L and M group was significantly increased(p < 0.05).Compared with L Group,the content of SOD in H group was significantly different(p < 0.01),and compared with M Group,the content of SOD in H group was significantly different(p < 0.01).(5)Compared with Group C,the skeletal muscle of Group C was slightly injured,the arrangement of muscle fibers was destroyed,the striations were disordered and some nuclei of muscle cells moved inward,the injury of skeletal muscle in L,M,H dose group and creatine control group were obviously improved,the transverse lines were clear and the fibers were arranged evenly.(6)Compared with Group C,the expression levels of AMPK m RNA and pgc-1αm RNA in group H were significantly increased(p < 0.05).(7)Compared with Group C,the expression levels of AMPK and p-AMPK in Group H were significantly increased(p < 0.05).(8)Compared with Group C,the expression of Bcl-2 protein was up-regulated in Group H,and the expression of Bax protein was down-regulated in group M(p < 0.05),and the ratio of Bcl-2/Bax was increased in Group H and group P,compound multi-dimensional coenzyme Q10 effervescent tablets have anti-apoptotic effect on mice skeletal muscle.Conclusion: Compound multi-dimensional coenzyme Q10 effervescent tablets can significantly improve exercise endurance,increase energy storage,and have anti-oxidation effect,the effervescent tablets may play an anti-fatigue role by regulating the expression of AMPK/ PGC-1α and Bcl-2/Bax pathway related proteins and genes in skeletal muscle. |
