The Modulating Mechanism Of FoXO3a In Denervated Skeletal Muscle Atrophy In Rats And The Treating Effects Of The Extract Of Ginkgo Biloba

Objective:To inspect the therapeutic effect and the influence on the FoxO3a/MAFbx pathway by the Extract of Ginkgo Biloba(EGB761) in myocytes of denervated gastrocnemius in rats.Methods:54adult female rats with initial body weight ranging from190g to210g were obtained from the physiology laboratory of Shanxi Medical University.They were divided randomly into three groups of six:A group (Denervated group,N=24),B group (Denervated+EGB treated group,N=24) and C group (Normal control group,N=6).Intraperitoneal injection anesthesia was induced with10%Chloral Hydrate(2ml·kg-1),then the sciatic nerve was identified and lifted through an incision on the lateral aspect of the mid-thigh of the right hind limb.For A and B group,a1-cm segment of the sciatic nerve was excised whereas for C group the nerve was not severed.The surgical incisions were closed and the animals were returned to their cages.B group(the denervated+EGB treated group) was given EGB761using gastric lavage(100mg·kg-1·d-1).Every6rats were killed by cervical dislocation at the day2,7,14,28for the denervated group and the day2,7,14,28for the denervated+EGB treated group.Their bilateral gastrocnemius were obtained.The individual muscle were weighed prior to freezing in liquid nitrogen and stored at-80℃until homogenization for RT-PCR and Western Blotting.then the right gastrocnemius were reserved and the protein p-FoxO3aS253,FoxO3a and MAFbx was tested using Western Blotting and the amount of mRNA of FoxO3a and MAFbx was detected using real-time PCR(RT-PCR).Finally,data were represented as the mean±SD and were analyzed using SPSS13.0.One-way analysis of variance and independent student’s t-test were used for the data of rates of muscle weights and p-FoxO3aS253,FoxO3a,MAFbx mRNA and protein expression in the gastrocnemius muscle of different groups. A two tailed probability value of less than0.05was considered to be significant.Result:the ratios of muscle weights were higher in EGB treated group(P<0.05),although were declining over time; the mRNA level and the protein concentration of both FoxO3a and MAFbx were lower after treating with EGB761,and the differences were significant at the day7,14,and 28(P<0.05). The phosphorelated level of FoxO3a was significantly higher in the EGB treated group at the same period of time.Conclusion:EGB761probably acts through the FoxO3a/MAFbx pathway to fight against skeletal muscle atrophy induced by denervation.