人参三醇皂苷对D-半乳糖诱导小鼠骨骼肌衰老的改善作用及其机制OA

Objective:To discuss the effect of Panaxatriol saponins(PTS)on D-galactose(D-gal)-induced skeletal muscle aging of mice,and to clarify its possible molecular mechanism.Methods:Seventy-two male C57BL/6J mice were randomly divided into control group,D-gal group,PTS group,and D-gal+PTS group.A D-gal-induced skeletal muscle aging model was established,and then PTS was administered;the general condition of the mice in various groups was observed;the weight of rectus femoris muscle of mice was measured and the sarcopenia index(SI)was calculated;HE staining was used to observe the pathomorphology of skeletal muscle tissue of the mice in various groups;Western blotting method was used to detect the expression levels of endoplasmic reticulum(ER)stress-related proteins in the eukaryotic translation initiation factor 2α(eIF2α)/activating transcription factor 4(ATF4)signaling pathway in skeletal muscle tissue of the mice in various groups.Results:The observation of general condition showed that compared with control group,the mice in D-gal group had sparse and poor quality hair,abnormal behavior,and decreased activity;compared with D-gal group,the mice in D-gal+PTS group showed significantly improved hair condition,improved behavioral state,and were more active.The measurement results showed that compared with control group,the body mass,left rectus femoris SI,and right rectus femoris SI of the mice in D-gal group were significantly decreased(P<0.01);compared with D-gal group,the body mass,left rectus femoris SI,and right rectus femoris SI of the mice in D-gal+PTS group were significantly increased(P<0.01).The HE staining results showed that compared with control group,the cross-section of rectus femoris muscle of the mice in D-gal group showed broken muscle fibers,nuclear internalization of myocytes,and significantly widened intercellular space were observed,showing the morphological changes of sarcopenia;no significant differences were observed in the above tissues of the mice in PTS group;compared with D-gal group,the myocytes of the mice in D-gal+PTS group had regular morphology,no widening of intercellular space,no nuclear internalization,and the muscle morphology was significantly improved.The Western blotting method results showed that compared with control group,the ratio of phosphorylated PERK(p-PERK)to PERK(p-PERK/PERK ratio),the expression levels of C/EBP homologous protein(CHOP)and ATF4 and activating transcription factor 5(ATF5)proteins,and the ratio of phosphorylated eIF2α(p-eIF2α)to eIF2α(p-eIF2α/eIF2α ratio)in skeletal muscle tissue of the mice in D-gal group were significantly increased(P<0.01);compared with D-gal group,the p-PERK/PERK ratio,p-eIF2α/eIF2α ratio,and the expression levels of ATF4 and ATF5 proteins in PTS group and D-gal+PTS group were significantly decreased(P<0.01).The Western blotting method results also showed that compared with control group,the expression level of B-cell lymphoma 2(Bcl-2)-associated X protein(Bax)in skeletal muscle tissue of the mice in D-gal group was significantly increased(P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.01);compared with D-gal group,the expression levels of Bax protein in skeletal muscle tissue of the mice in PTS group and D-gal+PTS group were significantly decreased(P<0.01),and the expression levels of Bcl-2 protein in skeletal muscle tissue of the mice in PTS group and D-gal+pts group were significantly increased(P<0.01).Conclusion:PTS can ameliorate D-gal-induced skeletal muscle aging of the mice and down-regulate the expression of proteins in the eIF2α/ATF4 signal pathway;its mechanism may be related to eIF2α/ATF4 signal pathway and molecular mechaism of Bax and Bcl-2.