ABSTRACT
Objective:To observe the effects of alendronate (ALN) on the expression of autophagy signaling pathway related proteins LC3, Beclin-1 and P62 in the muscle tissue of mice with denervated skeletal muscle atrophy, and to explore the potential molecular biological mechanism of ALN in the treatment of skeletal muscle atrophy.Methods:Thirty males C57BL/6 mice were divided into three groups with 10 mices in each group by random number method, including blank control group: sciatic nerve exposed without resection, model group: sciatic nerve exposed and resection, ALN group: sciatic nerve resection +ALN intervention. At the intervention stage, mices were given 1 mg/kg ALN by intragastric administration. The weight of gastrocnemius muscle was weighed by wet weight method. Atpase staining was used to distinguish muscle fiber types. HE staining was used to observe the arrangement and cross-sectional area of gastrocnemius muscle fibers in each group, and further quantitative analysis was performed by Image J 1.48 software. Western blotting and immunohistochemical staining were performed to detect the expressions of MHC and MuRF1 as well as LC3, Beclin-1 and P62 in gastrocnemius tissues of each group.Results:The weight of gastrocnemius muscle in the model group 137±7.80 mg was significantly lower than that in the blank control group 203±10.34 mg, which proved that the denervation muscle atrophy mouse model was successfully established. After intervention, the gastrocnemius muscle weight of ALN group 177±11.65 mg was significantly higher than that of model group, and the muscle mass was significantly improved. HE staining showed that muscle fibers in the model group were loosely arranged and the cross-sectional area was significantly smaller than that in the blank control group, and there were more blue stains among muscle fibers. Atpase staining showed that the distribution of type II muscle fibers in the model group was increased compared with that in the blank control group, and the distribution of type II muscle fibers in the ALN group was decreased compared with that in the model group, but higher than that in the blank control group. The results showed that the most widely distributed muscle fiber cross-sectional area was 600-800μm 2 in the blank control group, 200-400 μm 2 in the model group, and 400-600 μm 2 in the ALN group. The results of quantitative calculation of muscle fiber cross-sectional area by Image J 1.48 showed that the mean value of muscle fiber cross-sectional area in the model group was (352±18) μm 2, which was significantly reduced compared with the blank control group 794±20 μm 2. After ALN treatment, muscle fiber cross-sectional area recovered somewhat. The mean muscle fiber cross-sectional area of ALN group was 578±23 μm 2, which increased muscle fiber cross-sectional area by 29%. Western blotting results showed that the expressions of MHC, LC3 and Beclin-1 in model group were significantly lower than those in blank control group ( P<0.05), while MuRF1 and P62 proteins were significantly higher than those in blank control group ( P<0.05). The MHC, LC3 and Beclin-1 proteins in ALN group were significantly higher than those in model group (0.12±0.01 vs. 0.10±0.003, 0.15±0.02 vs. 0.10±0.02, 0.13±0.03 vs. 0.09±0.04). MuRF1 and P62 proteins in ALN group were significantly lower than those in model group (0.10±0.004 vs. 0.15±0.01, 0.16±0.03 vs. 0.20±0.03). MHC immunohistochemical staining showed that the expression of MHC in gastrocnemius of mice in model group was significantly lower than that in blank control group, and the expression of MHC in gastrocnemius of mice in ALN group was higher than that in model group ( P<0.05). Conclusion:ALN has a therapeutic effect on skeletal muscle atrophy, and its mechanism may be realized by moderately activating the LC3/Beclin-1 autophagy signaling pathway.
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Objective To investigate biomechanical characteristics of femoral neck fracture with different reduction qualities. Methods Three cases of Sawbones artificial femoral models were selected, and two cases of Pauwel III femoral neck fracture were modeled. Three cannulated screws were inserted into the models in the form of inverted triangle to fix the fracture. Two cases maintained different reduction qualities (defined as Model 1 and Model 2). In the 3 third case, no modeling operation was performed (defined as intact model). Then the strain gauges were respectively pasted on regions of interest of the 3 femoral models. Finally, the femur model was applied with the vertical load on mechanical testing machine. Results When the displacement of femoral head reached 4 mm, the average load of intact model, Model 1 and Model 2 was (236.30±5.35), (196.57±3.56), (69.50±2.95) N, showing significant differences. When the displacement of femoral head reached 5 mm, the average load of intact model, Model 1 and Model 2 was (276.7±3.40)，(232.93±2.64)，(80.83±4.54) N, showing significant differences. Conclusions The lower the reduction quality of the femoral neck fracture, the weaker the ability of the femur to bear stress, the higher the probability of nonunion, re-fracture and femoral head necrosis in the process of postoperative rehabilitation.
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Sarcopenia, referred to as myopenia, is a systemic syndrome characterized by decreased muscle mass and muscle strength, and decline of motor function.The elderly are a high incidence group of myopenia.With the aging of the world's population becoming increasingly severe, the incidence rate of sarcopenia has also increased, which has brought a heavy burden to the elderly family and society, and has become an important social health problem for the elderly.At present, there are more and more researches on sarcopenia, but the pathogenic factors of sarcopenia are complex and diverse.The prevention and treatment of sarcopenia still need to be further explored and studied.The establishment of an ideal animal model is the key premise and basis for the related research of sarcopenia.In this paper, the different modeling methods, advantages and disadvantages as well as the scope of application of sarcopenia animal models are described, which can provide reference and help for the subsequent animal experimental research of sarcopenia.
ABSTRACT
Venous thromboembolism (VTE) is a kind of venous disorder that the abnormal condensation of blood within the vein,leading to complete or incomplete vein obstruction.VTE is mainly a combination of deep vein thrombosis (DVT)and pulmonary embolism (PE) and is an important complication after major orthopedic surgery (total hip arthroplasty,total knee arthroplasty,hip fracture surgery).Foreign literature reported that incidence rate of VTE after arthroplasty was as high as 42％-57％.Conventional notion was that DVT and PE were two different but interrelated types of VTE,while the latest research reported that the formation of DVT and PE after arthroplasty may be two events individually.Prevention of VTE after major orthopedic surgery includes general,pharmacological and mechanical methods.The efficacy of physical combined with pharmacological methods was better than drug prevention alone in preventing distal DVT.Dabigatran,apixaban,rivaroxaban and other new oral anticoagulants were better than low molecular weight heparin and other traditional medicines in effectiveness and safety.The effects of low molecular weight heparin are remarkable,while it cannot take orally.A recent study found that staged VTE prophylaxis,namely patients received low molecular weight heparin injection in hospital,and received aspirin,rivaroxaban or dabigatran orally after discharge is safe and effective in prevention of VTE.