Background: Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathol...Background: Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis.This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.Methods: Twenty-four mice were randomly allocated to normal control group (n =6), blank control group (n =6), VEGF gene transfection group (n =6), and NGF gene transfection group (n =6).The model of left hindlimb ischemia model was established by ligating the femoral artery.VEGF165 plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively.Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction.The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining.NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.Results: On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group.The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P 〈 0.05).The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P 〈 0.05).Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P 〈 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P 〉 0.05).The type Ⅰ skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P 〈 0.05).Conclusions: NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type Ⅰ muscle fiber expression in ischemic limbs.展开更多
This paper presents a bioelectrochemical model for the activation of action potentials on sarcolemma and variation of Ca2+ concentration in sarcomeres of skeletal muscle fibers.The control mechanism of muscle contract...This paper presents a bioelectrochemical model for the activation of action potentials on sarcolemma and variation of Ca2+ concentration in sarcomeres of skeletal muscle fibers.The control mechanism of muscle contraction generated by collective motion of molecular motors is elucidated from the perspective of variable-frequency regulation,and action potential with variable frequency is proposed as the control signal to directly regulate Ca2+ concentration and indirectly control isometric tension.Furthermore,the transfer function between stimulation frequency and Ca2+ concentration is deduced,and the frequency domain properties of muscle contraction are analyzed.Moreover the conception of "electro-muscular time constant" is defined to denote the minimum delay time from electric stimulation to muscle contraction.Finally,the experimental research aiming at the relation between tension and stimulation frequency of action potential is implemented to verify the proposed variable-frequency control mechanism,whose effectiveness is proved by good consistence between experimental and theoretical results.展开更多
文摘Background: Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis.This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.Methods: Twenty-four mice were randomly allocated to normal control group (n =6), blank control group (n =6), VEGF gene transfection group (n =6), and NGF gene transfection group (n =6).The model of left hindlimb ischemia model was established by ligating the femoral artery.VEGF165 plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively.Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction.The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining.NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.Results: On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group.The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P 〈 0.05).The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P 〈 0.05).Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P 〈 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P 〉 0.05).The type Ⅰ skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P 〈 0.05).Conclusions: NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type Ⅰ muscle fiber expression in ischemic limbs.
基金supported by the National Natural Science Foundation of China (Grant No. 61075101)the Research Fund of State Key Laboratory of MSV,China (Grant No. MSV-2010-01)+1 种基金the Medical and Technology Intercrossing Research Foundation (Grant No. YG2010ZD101)the Science and Technology Intercrossing Research Foundation of Shanghai Jiaotong University
文摘This paper presents a bioelectrochemical model for the activation of action potentials on sarcolemma and variation of Ca2+ concentration in sarcomeres of skeletal muscle fibers.The control mechanism of muscle contraction generated by collective motion of molecular motors is elucidated from the perspective of variable-frequency regulation,and action potential with variable frequency is proposed as the control signal to directly regulate Ca2+ concentration and indirectly control isometric tension.Furthermore,the transfer function between stimulation frequency and Ca2+ concentration is deduced,and the frequency domain properties of muscle contraction are analyzed.Moreover the conception of "electro-muscular time constant" is defined to denote the minimum delay time from electric stimulation to muscle contraction.Finally,the experimental research aiming at the relation between tension and stimulation frequency of action potential is implemented to verify the proposed variable-frequency control mechanism,whose effectiveness is proved by good consistence between experimental and theoretical results.