The Effects Of Urolithin B On Sarcopenic Mouse Model Induced By Dexamethasone

ObjectiveBased on the establishment of sarcopenic mouse model induced by dexamethasone,we studied the effects of urolithin B on the sarcopenic mouse model induced.MethodsTwenty-four Kunming male mice were randomly divided into two groups:N group(normal group,n=8),M group(model group,n=16).the normal group was treated with 0.9% normal saline and the model group was treated with dexamethasone sodium phosphate injection,the two groups were all given subcutaneous injection every day.The body composition of these mice were measured by Echo MRITM,the muscle strength in the limbs of these mice were measured by mouse grip instrument,Muscle function was detected by wheel fatigue.The three methods were used to evaluate the sarcopenic mouse model.After determining the success of the model,the mice were intervened.M group were randomly divided into two subgroups,one subgroup was given 0.9% physiological salt and the other subgroup was given urolithin B,and then fallen into three groups:normal control group(A group),model compare group(B group),model treatment group(C group),each group has 8 mice,the intragastric administration frequency was 7d/w.Continued to use the second method mentioned above,the body composition,the muscle force and the function of those muscle were measured after treatment.The blood of these mice was collected from heart after anesthesia,the concentration of inflammatory factors in serum were measured by Kit.We separated the soleus of these mice,made pathological section,HE stains and measured the cross-sectional area of muscle fibers.The difference of the m RNA expression level of Atrogin-1,Mu RF1,Myo D,myogenin,LC3 b and p62 in the skeletal of these mice was measured by fluorescence quantitative PCR.ResultsThe fisrt part: At the tenth day of model establishment,the weight and muscle mass in body composition in model group was significantly lower than that in normal control group(P<0.05).The muscle strength in model group was significantly lower than that in control group(P<0.05);The second part:After intragastric administration in urolithin B,there was no significant difference in body weight,muscle mass,grip force between B group and C group(P>0.05),but in C group,the grip force showed an increasing trend;there was a significant difference in the number of dropping between B group and C group(P < 0.05).The number of dropping in the C group was decreased significantly than B group(P<0.05);there was a significant difference in gastrocnemius cross-sectional area between model group and normal group whether treated with urolithin or not(P>0.05),but in model group,the cross sectional area showed an increasing trend;there was no significant difference in serum factors TNF-??IFNr?IL-1b?MCP-1?IL-6?KC between those three groups whether treated with urolithin or not(P>0.05),The difference of IP10 between model group and normal group was statistically significant(P<0.05),but there was no difference appeared whether treated with urolithin or not;The expression level of Myogenin and Myo D in the B/C group was respectively significantly lower than that in A group(P<0.05),and C group was respectively increased than that in B group(P<0.05);The expression level of Mu RF-1 and Atrogin-1 was respectively significantly than that in A group(P<0.05),and C group was respectively decreased than that in B group(P<0.05);The expression level of P62 was significantly declined than that in A group(P<0.05),the expression level of LC3 b was significantly increased than that in A group.P62 in the Urolithin group was respectively higher than that in Dex group(P<0.05),and LC3 b is opposite,and the difference between the group of control and Urolithin is significant.ConclusionsIntragastric administration of urolithin B improved the muscle strength and function of dexamethasone-induced sarcopenic mice model by regulating the Ubiquitin proteasome system and autophagy-lysosomal system,but it has little effect on body composition.