| Total parenteral nutrition(TPN)has been widely used in clinical practice as an important part of nutritional supportmethods since 1960s.TPN can provide all kinds of nutrients,such asamino acids,fatty acids et.al via vein,which helps patients who are unable to eat normally can still maintain the nutritional status.TPN is an irreplaceable means of treatment and has saved many lives.For patients with nutritional risk,TPN support can significantly reduce mortality and length of hospital stay,accelerate patient recovery,and improve clinical outcomes.For the patients in the period of operation or the patients under stress and injury,the homeostasis of the body is usually unbalanced,which was in a state of high catabolism.If not replenish enough nutrients on time,the patient will appear to varying degrees of protein consumption,skeletal muscle will be significantly reduced.Skeletal muscle loss is closely related to clinical outcome.Skeletal muscle consumption indicates a reduction in body protein and muscle strength,which will increase the incidence of respiratory problems and the risk of pneumonia.The deficiency of protein can obviously affect the immune defense of patients,increase the risk of infection complications,affect the structure and function of organs,and accelerate the failure of multiple organs.A number of studies have shown that the utilization rate of nutrients provided by PN is not as high as EN.In the case of the same amount of calories and nitrogen,the weight gain and nitrogen retention of enteral nutrition patients were better than those of parenteral nutrition.A number of studies have found that early PN does not prevent weight loss and loss of skeletal muscle.However,the cause and mechanism of skeletal muscle loss caused by parenteral nutrition is not clear.At present,the study of PN on protein metabolism of skeletal muscle in critically ill patients is mainly focused on the relationship between muscle loss and muscle weakness,prolonged mechanical ventilation time,fatigue and recovery time.Previous studies have shown that early administration of nutrients may inhibit skeletal muscle autophagy in surgical patients.This project is aim to analyze the changes in the use of parenteral nutrition in surgical patients during skeletal muscle by the collection of clinical patient data;and using a mouse model of parenteral nutrition,electron microscopy,western blot,ELISA,immunofluorescence,mass spectrometry,to confirm that the use of parenteral nutrition is more likely to cause the loss of skeletal muscle in mice comparing with normal diet,and the investigating the possible molecular mechanism.In addition,figure out the changes of skeletal muscle mass and the expression of protein metabolism for the mice with ulcerative colitis after using parenteral nutrition.The results of this study will clarify the changes of skeletal muscle metabolism in normal mice and ulcerative colitis mice,and provide a theoretical basis for reducing the metabolic complications of parenteral nutrition.PRAT ⅠThe changes of skeletal muscle content of surgical patients with TPN Objective:To observe the changes of skeletal muscle before and after the use of TPN in surgical inpatients,and to determine whether TPN affects the skeletal muscle loss during hospitalization.Method:The hospitalized patients with intestinal failure or having enteral nutrition contraindication receiving continuous TPN for a period of time were collected.The patients’ basic statistical data and CT images were recorded,and the skeletal muscle area before and after TPN was calculated.It was confirmed whether the use of TPN has the impact on the area of skeletal muscle in surgical inpatients.Results:A total of 124 patients admitted to the Department of general surgery in our hospital from January 2014 to December 2016 were enrolled.For patients with radioactive enteritis(55 cases),the skeletal muscle decreased significantly(P<0.001)after 15 + 10.15 days TPN;but the subcutaneous fat area(p=0.721)and visceral fat area(p=0.136)showed no significant difference.Conclusion:The use of TPN in surgical patients was mainly within 2 weeks.For the patients with radiation enteritis,there would be a decline in skeletal muscle content after the use of TPN,while subcutaneous fat and visceral fat did not significantly change;and the decreased skeletal muscle content was associated with the duration of TPN use.PRAT ⅡThe impact of total parenteral nutrition on skeletal muscle protein metabolism in normal mice model Objective:To observe the impact of different nutrition methods on mice’s skeletal muscle protein metabolism in mice model.It is compared the difference of TPN and total enteral nutrition on protein metabolism of skeletal muscle in mice,and explored the possible molecular mechanism.Method:20 normal mice were randomly divided into two groups:normal diet group(group TEN,n=10)and total parenteral nutrition group(group TPN,n=10).Body weight,gastrocnemius muscle wet weight,observation of gastrocnemius by light microscopic and electron microscopic,the expression of related markers of protein metabolism were measured by WB method and the expression of pro-inflammatory cytokines were assayed in serum,intestinal and gastrocnemius muscle by ELISA.Results:During the 5 days of nutrition intervention,the body weight of mice in group TEN did not change significantly,while the body weight of mice in TPN group decreased gradually.Compared with the TEN group,the gastrocnemius muscle wet weight of TPN group was significantly reduced,the cross-sectional area of gastrocnemius muscle fibers was significantly decreased,and the ultrastructure of muscle fibers was significantly damaged.The protein synthesis pathway marker protein levels in gastrocnemius muscle have no significant difference between both groups of mice.But the protein expression of MURF-1 in gastrocnemius muscle in the TPN group and the protein ratio of LC3 Ⅱ and LC3 Ⅱ/LC3 Ⅰ was significantly higher than TEN group.The protein level of Beclin-1 was significantly higher than that of TEN group.Conclusion:Compared with enteral nutrition,total parenteral nutrition can not prevent skeletal muscle loss in normal mice.TPN activates the ubiquitin proteasome pathway and the autophagic-lysosomal pathway in skeletal muscle.PRAT ⅢThe impact of total parenteral nutrition on skeletal muscle protein metabolism in mice model with ulcerative colitisObjective:To observe the impact of different nutrition methods on mice’ s skeletal muscle protein metabolism in animal experiments.Comparing the difference of TPN and total enteral nutrition on protein metabolism of skeletal muscle in mice with ulcerative colitis,,and exploring the possible molecular mechanism.Methods:The 60 mice with ulcerative colitis were randomly divided into two groups:normal diet group(group TEN,n=30)and total parenteral nutrition group(group TPN,n=30).The time of the two groups of different nutrition interventions were 3 days,5 days and 7 days,respectively.Body weight,gastrocnemius muscle wet weight,observation of gastrocnemius by light microscopic and electron microscopic,the expression of related markers of protein metabolism were measured by WB method and the expression of pro-inflammatory cytokines was assayed in serum,intestinal and gastrocnemius muscle by ELISA.Results:The body weight of mice in TEN group decreased first and then increased gradually,and the body weight of mice in TPN group was gradually decreased to Day7.Compared with the TEN group,the gastrocnemius muscle wet weight of TPN group was significantly reduced,the cross-sectional area of muscle fiber was significantly decreased,and the ultrastructure of muscle fiber was significantly damaged.The protein synthesis pathway marker in gastrocnemius muscle has no significant difference between the two groups of mice.But the protein level expression of MURF-1 in gastrocnemius muscle of the TPN group and the protein ratio of LC3 Ⅱ and LC3 Ⅱ/LC3 Ⅰ was significantly higher than TEN group.The protein level of Beclin-1 was significantly higher than that of TEN group.Conclusion:Compared with enteral nutrition,parenteral nutrition will activate muscle autophagy-lysosomal pathway and ubiquitin proteasome pathway in mice with ulcerative colitis,increasing skeletal muscle protein degradation,which will lead to the loss of skeletal muscle protein.This may be related with the TPN induced damage of the intestinal barrier function and the higher level of proinflammatory cytokines in serum,intestine and skeletal muscle. |
