| Objective: In this study,the rat model of exercise fatigue was established by exhaustive swimming to explore the anti-fatigue mechanism of different doses of Zuogui Pill and its protective effect on rat hippocampal neurons.Methods: 50 rats(SD,6-week-old,male)were randomly divided into three groups:blank control group(group C),exercise control group(group E),Zuogui pill-high(group ZEH),low(group ZEL)and middle(group ZEM).Except for the control group,all the other groups were given exhaustive swimming for 4 weeks.Group C and group E were given2ml/d normal saline,and the drug group was given 2ml/d Zuogui pill suspension at high,low and medium doses.After the last exhaustive swimming,the rats were dissected and the blood and hippocampal tissue were collected.The activities of creatine kinase(CK),urea nitrogen(BUN),inducible nitric oxide synthase(i NOS),superoxide dismutase(SOD),malondialdehyde(MDA),corticosterone(C),5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE)were detected according to the kit instructions.The m RNA expression of brain-derived neurotrophic factor(BDNF)and tyrosine protein kinase B(Trk B)was detected by RT-q PCR,and the protein expression of BDNF and TrKB was detected by WB.Results:(1)The results of body weight and exhaustion time showed that compared with group C,the body weight of rats in each exercise group decreased significantly,compared with group E,the swimming exhaustion time of rats in ZEH and ZEL groups was significantly prolonged,and that in ZEM group was significantly prolonged,but there was no significant difference among the treatment groups.(2)The results of serum biochemical indexes showed that the levels of serum CK,BUN and C in group E were significantly higher than those in group C(p < 0.001),and the levels of CK in ZEL and ZEM groups were significantly higher than those in group E(p < 0.001).Compared with group E,the levels of serum CK,BUN and C in each group decreased significantly,but there was no significant difference among each group.(3)The results of serum and hippocampal i NOS detection showed that the serum and hippocampal i NOS activity in E group,ZEH group and ZEL group were significantly higher than those in C group(p < 0.001).There was no significant difference in ZEM serum i NOS and hippocampal i NOS.Compared with group E,there was no significant difference between each administration group(p > 0.05),and there was no significant difference between each administration group(p > 0.05).(4)The results of oxidation-antioxidation indexes in serum and hippocampus showed that the contents of MDA in serum and hippocampus in group E were significantly higher than those in group C,but there was no significant difference in SOD,and there was no significant difference in MDA and SOD in each group.Compared with group E,MDA decreased significantly and SOD increased significantly in each group.Compared with each administration group,the ZEM group increased the serum and hippocampal SOD of rats most obviously.(5)The results of hippocampal neurotransmitters showed that compared with group C,5-HT in group E increased significantly,while DA and NE decreased significantly(p <0.001).5-HT decreased significantly in group ZEH,but there was no significant difference in DA,NE and ZEL group.In ZEM group,5-HT decreased significantly(p < 0.001),while DA and NE increased significantly(p < 0.05).Compared with group E,5-HT decreased significantly,DA and NE increased significantly in each group,5-HT increased and DA and NE decreased most significantly in ZEM group.(6)Compared with group C,the expression of BDNF,TrKBm RNA and protein in hippocampus of group E was significantly higher than that of group C,and that of group ZEH and ZEM was significantly higher than that of group C(p < 0.001),and there was no significant difference in group ZEL(p > 0.001).Compared with group E,the expression of m RNA and protein in group ZEH and ZEM was significantly increased,and there was no significant difference in group ZEL.Compared with each treatment group,the expression of BDNF,TrKBm RNA and protein in ZEM group was the most up-regulated.Conclusion:(1)Zuogui Pill can significantly prolong the swimming exhaustion time and improve the exercise ability of exercise fatigue rats.(2)Zuogui Pill plays an anti-oxidative role by regulating the metabolism of free radicals,reducing the level of lipid peroxidation in serum and hippocampus,increasing the activity of antioxidant enzymes and reducing oxidative stress.(3)Zuogui Pill plays a role in anti-exercise-induced central fatigue by regulating the level of hippocampal neurotransmitters,reducing neuronal injury and improving the excitability of central nervous system.(4)Zuogui Pill plays a neuroprotective role in hippocampus by up-regulating the expression of BDNF and TrKB.(5)The medium dose Zuogui Pill has the best anti-fatigue effect. |
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