| Sarcopenia is an age-related progressive and widespread disease characterized by "loss of skeletal muscle mass and function".It is an elderly syndrome characterized by decreased muscle mass,muscle strength and activity.In recent years,studies have found that the decline of physical functions such as dyskinesia and falls is closely related to the decrease of skeletal muscle mass and muscle strength,which is the main reason for the decline of the quality of life of the elderly.At the same time,clinical observation also found that Diabetes Mellitus type2(T2DM)patients had such a more prominent performance.Therefore,some scholars have suggested that T2DM has an aggravating effect on the degeneration of skeletal muscles,and TDS can be regarded as another chronic complication of diabetes,which has attracted wide attention from scholars.However,the clinical manifestations and body composition changes have been reported differently,and the related pathogenesis research is still under discussion.In particular,the occurrence and development mechanism of TDS in elderly T2DM patients needs to be clarified.ObjectiveOn the one hand,to explore the internal relationship and possible law between the age,course of disease,obesity index,body composition and the occurrence of sarcopenia in T2DM patients;On the other hand,by replicating the old T2DM rat model,observe the changes of the "quantity"and "quality" of the old T2DM sarcopenia and limb skeletal muscle,and explore the possible mechanism of the old T2DM sarcopenia from the pathway of protein anabolism.At the same time,the experimental animals of the old T2DM sarcopenia were intervened with TDS,a medicine for invigorating the spleen and Qi,to clarify its effect and possible pathway,Part of the interpretation of traditional medicine "spleen dominates muscle"theory.Methods1.Clinically,the changes of population composition and obesity index between elderly T2DM patients and elderly normal people were collected.The changes of disease course,glucose and lipid metabolism and related indexes of sarcopenia in elderly T2DM patients were observed,and the possible influencing factors of T2DM sarcopenia were analyzed by binary logistic regression.2.The old T2DM rat model was established by the method of old rats and continuous feeding with high-fat diet and intraperitoneal injection of low-dose STZ.The treadmill running time and grasping force of rats in each group were measured after 4 weeks of drug intervention.After the test,the rats were killed under anesthesia,and the weight of gastrocnemius muscle,blood glucose,insulin,glycosylated serum protein,total cholesterol,triglyceride,high-density lipoprotein and low-density lipoprotein were measured.At the same time,the gastrocnemius muscle tissues of rats in each group were observed pathologically.3.Molecular mechanism of Zhuang drug TDS in the treatment of senile T2DM with sarcopenia based on protein anabolic pathway:take rat skeletal muscle tissue,and use PCR and Western blot assay to determine the mRNA and protein expression levels of PI3K/Akt/mTOR pathway related factors such as PI3K,Akt,mTORC1,S6K1 and 4ebp1 in skeletal muscle,so as to investigate the effect of Zhuang drug TDS on protein anabolism in skeletal muscle of senile T2DM rats.Results1.Compared with the elderly normal population,the incidence of sarcopenia in elderly T2DM patients was significantly higher,and there was significant difference in statistical analysis(p<0.05).ASMI in elderly T2DM men was significantly lower than that in elderly normal men(p<0.05);ASMI in elderly T2DM women was significantly lower than that in elderly normal women(p<0.01).Body composition analysis:the body fat rate of men in elderly T2DM patients was significantly higher than that of men in elderly normal population(p<0.05);Male muscle mass/fat mass,female muscle mass/fat mass,male muscle mass/BMI,female muscle mass/BMI,female skeletal muscle mass/fat mass,male skeletal muscle mass/BMI and female skeletal muscle mass/BMI in elderly T2DM patients were lower than those in elderly normal population,and the difference was statistically significant(p<0.05);There was significant difference between male ASMI and female ASMI(p<0.001);The course of disease in elderly T2DM patients with sarcopenia was significantly different from that in elderly T2DM patients without sarcopenia(p<0.01);There was no significant difference in age,systolic blood pressure,diastolic blood pressure,fasting blood glucose and glycosylated hemoglobin between elderly T2DM patients with sarcopenia and elderly T2DM non sarcopenia.Body composition analysis:the body fat rate of male patients with T2DM sarcopenia was significantly higher than that of non sarcopenia patients(p<0.05);The muscle mass/fat mass of elderly T2DM sarcopenia men was significantly lower than that of elderly T2DM non sarcopenia men(p<0.05);The muscle mass/BMI of elderly T2DM sarcopenia men was significantly lower than that of elderly T2DM non sarcopenia men(p<0.05);The skeletal muscle mass/BMI of elderly T2DM sarcopenia men was significantly lower than that of elderly T2DM non sarcopenia men(p<0.001);The skeletal muscle mass/BMI of elderly T2DM sarcopenia women was significantly lower than that of elderly T2DM women(p<0.05).Binary logistic analysis showed that the possible influencing factors of sarcopenia in T2DM were course of disease,body fat rate and BMI.The longer the course of disease,the higher the body fat rate and the lower the BMI,the more prone to sarcopenia.2.Compared with the model group,TDS-H could increase the wet weight of gastrocnemius muscle in model rats(p<0.05).TDS-H can reduce blood glucose,increase insulin and reduce the level of glycosylated serum protein in model rats to a certain extent.TDS can reduce the levels of TG and LDL,reduce the level of TC and improve the level of HDL to a certain extent,among which TDS-H has a better effect.There was no difference in treadmill exercise time before modeling in each group;After administration,there was a significant difference in treadmill running time between the model group and the normal group(p<0.001).TDS-H could significantly increase the treadmill running time of model rats(p<0.05),but there was no significant difference in other groups.In terms of grasping force,there was significant difference between the model group and the normal group(p<0.05),and there was significant difference between TDS-M group and TDS-H group and the model group(p<0.05),but there was no difference in other groups.In terms of pathological tissue,he staining showed that compared with TDS-H group,gastrocnemius muscle cell edema was not obvious,and the number of nuclei and gastrocnemius fibers were also improved.Oil red staining showed that the fat content in the model group was higher than that in the normal group.After the intervention of Zhuang medicine TDS,the fat content decreased.3.The effect of Zhuang medicine TDS on the mRNA expression of related factors in mTOR/Akt/PI3K pathway.Compared with the normal group,the mRNA expression levels of mTOR,Akt,PI3K,S6K1 and 4ebp1 in the model group were down regulated in varying degrees,with statistical difference.TDS-M group and TDS-H group promoted the mRNA expression levels of mTOR,PI3K,S6K1 and 4ebp1,and the difference was statistically significant.Although there was no difference in the regulation of Akt by TDS,TDS-M and TDS-H up-regulated the expression level of Akt mRNA by 40.7%and 23.9%respectively.Compared with the normal group,the protein expression levels of mTOR,Akt,PI3K,S6K1 and 4ebp1 in the model group were significantly lower.Compared with the model group,the expression of Akt,PI3K and S6K1 in TDS-H group was significantly higher than that in the model group;The up regulation of mTORCl and 4ebp1 was not statistically significant,but increased by 26.7%and 19.6%respectively compared with the model group.Conclusions1.The incidence of sarcopenia in elderly T2DM patients was significantly higher than that in elderly normal population.The longer the course of disease,the smaller the BMI and the higher the body fat rate,the more prone to sarcopenia in elderly patients with T2DM.2.The effect and mechanism of Zhuang medicine TDS in the treatment of senile T2DM myopenia are directly related to regulating mTOR/Akt/PI3K Signal Pathway and promoting protein synthesis.3.The study on the effect and mechanism of TDSin the treatment of senile T2DM sarcopenia partly explains the theoretical connotation of"spleen dominates muscles and limbs" in traditional medicine. |
