| Background and ObjectiveMicrogravity could induce a series of changes on the physiological state in humans and animals, among which skeletal muscle atrophy is stirking. Until now, the mechanism of muscle atrophy under microgravity is still unclear and there is no specific medical intervention. The PI3K/AKT pathway and MAPK pathway are the main pathways transducting the siganals from the extracellular to intracellular, as well as regulating cell differentiation, proliferation, apoptosis, et al. Previous studies suggested that these signal pathways maybe participated in the pathogenesis of skeletal muscle atrophy under microgravity. This research was carried out to explore the role of the PI3K/AKT pathway and MAPK pathway and identify the effect of Xuefuzhuyu capsules and Dl-3-n-butylphthalide in muscle atrophy under miacrogravity.MethodsTail-suspended rat was taken as the animal model of simulated microgravity.40homologous Sprague-Dawley female rats (aged10weeks,weighing200-250g) were randomly divided into four groups, including control group (CON), tail-suspended group (SUS), tail-suspended+Xuefuzhuyu capsule group (XFZY), tail-suspended+Dl-3-n-butylphthalide group (NBP). The25mg/kg/d Xuefuzhuyu and20mg/kg/d Dl-3-n-butylphthalide were administrated to the XFZY Group and NBP Group respectively, while the lml/d solvent to the CON Group and SUS Group. All the rats received the intragastric administration at eight o’clock every day.(1) The soleus morphological changes were measured, including the wet weight of body weight, the cross-sectional area of fibre cells, the fiber type distribution on the myosin staining, et al.(2) The protein and mRNA expression of PI3K/AKT, the phosphorylation of ERK and JNK and some downstream proteins such as BAX and Cyto-c were detected by Western-blot and RT-PCR. (3) The caspase-3activity and the soleus cells’apoptosis degree were detected by UV spectrophotometer and TUNEL assay.Results:40rats were all taken in the result analysis, without any loss.(1) Compared with the CON Group, the wet weight of body weight of the SUS group decreased56.39%. The average wet weight of body weight of XFZY Group and the NBP Groupe increased14.49%and13.85%respectively. The wet weight of body weight between XFZY Group and SUS Group was significant different. Compared with the control group, the fiber proportion of Type I in the other three groups were all significantly reduced, and the medicine did not reverse the conversion of type I to type Ⅱ.(2) The content of P-AKT and GRP78decreased under simulated microgravity, while the content of GSK-3β increased. Both Xuefuzhuyu and dl-3-n-butylphthalide could increase the activity of Akt and GRP78and decrease the activity of GSK-3β.But the content of P-AKT suffered the greatest effect in XFZY Group, while the GRP78in NBP Group.(3) Simulated microgravity decreased the expression of P-ERK and increased P-JNK after30d tail-suspension.The protectant pathway was promoted and the inhibitive pathway was inhibited after the intervention of this two drugs..(4) The caspase3and the number of the positive apoptosis muscle nucleus were increased after30days of tail-suspended. But both the XFZY Group and the NBP Group could inhibit these changes.Conclusions(1) Apoptosis maybe play an important role in the SOL atrophy under simulated microgravity, which through inhibiting the PI3K/AKT, ERK signaling pathway, promoting the JNK pathway.(2)Xuefuzhuyu and dl-3-n-butylphthalide do reduce the atrophy by simulated microgravity through the PI3K/AKT and MAPK pathway. |
PDF Full Text Request