黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后氧化应激及微循环的影响
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摘要
骨骼肌钝挫伤是运动医学领域中常见的一类创伤,发生率10%～55%不等,损伤后骨骼肌愈合时间长且多为疤痕愈合,严重影响运动功能,是目前运动医学领域研究的热点与难点。研究表明骨骼肌损伤后可立即再生,但骨骼肌再生能力有限,结构及功能恢复常常不完全,愈合缓慢,并伴有一定程度的瘢痕化,易再次发生损伤。研究发现骨骼肌损伤后的早期,损伤局部的微血管首先遭到破坏,出现细胞膜损害,内皮细胞肿胀,微血管渗透性增加,周围血管出血,甚至无法控制的血栓形成,从而导致膜磷脂退变,自由基的聚集以及炎性反应诱导的氧化应激,进一步加剧周围正常骨骼肌组织的损害。国内外研究表明,钝挫伤导致的微循环紊乱和继发的组织损害在损伤后24h时最为严重。局部微循环障碍、损伤细胞渗出物氧化均可导致组织活性氧簇(ROS)的过度生成,ROS可进一步损害脂质膜从而加重骨骼肌细胞的损伤,甚至坏死,而抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶)可对抗氧化应激损伤,保护骨骼肌细胞。因此如何早期改善局部微循环,减少自由基的生成,提高抗氧化酶的活性,已成为骨骼肌损伤修复的研究热点之一。我们先前的研究已经证明黄芪丹参注射液具有促进骨骼肌肌球蛋白重链表达、缩短肌肉愈合时程以及提高愈合质量的作用,但其促进愈合的机制目前尚不清楚。本研究目的旨在通过观察黄芪丹参注射液对骨骼肌钝挫伤后氧化应激及早期微循环的影响,探讨黄芪丹参注射液在促进骨骼肌愈合过程中是否具有抗氧化应激、改善微循环、保护损伤骨骼肌的作用,从而为其进一步的临床应用提供实验依据
本实验第一部分研究黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后氧化应激的影响。通过测定骨骼肌钝挫伤以后组织中脂质过氧化产物丙二醛,抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶)的活性来探讨黄芪丹参注射液是否是通过清除自由基,提高抗氧化酶活性从而促进了骨骼肌损伤后的愈合
本实验第二部分研究黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后微循环的影响。通过测定骨骼肌钝挫伤后大鼠全身血流动力学的改变,骨骼肌的湿、干重比值,以及损伤局部微动脉的管径变化,毛细血管流速变化,观察给予黄芪丹参注射液后是否具有改善微循环,减轻水肿从而促进损伤骨骼肌的愈合。
第一部分
黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后氧化应激的影响
目的:观察黄芪丹参注射液对大鼠骨骼肌钝挫伤后修复过程中氧化应激的影响
方法:72只雄性SD大鼠随机分为中药治疗组、生理盐水组、自然愈合组,每组24只。采用打击装置造成右侧腓肠肌中段钝挫伤模型,分别于损伤局部注射黄芪丹参注射液、生理盐水、不作处理。另6只做空白对照(未经任何处理)。于损伤后1、4、7和14天取腓肠肌测定丙二醛(MDA)含量、过氧化氢酶(CAT)活性、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-px)活性。
结果:与生理盐水组和自然愈合组相比,中药组腓肠肌SOD、GSH-px的活性在1、4、7天明显升高(P＜0.05),而CAT活性则无明显变化(P＞0.05)。中药组腓肠肌MDA含量在伤后4、7天明显低于生理盐水组和自然愈合组(P＜0.05)。
结论:黄芪丹参注射液可明显减少氧化产物MDA含量,减轻骨骼肌钝挫伤愈合过程中的氧化性损伤,并显著提高骨骼肌还原酶SOD和GSH-px的活性。
第二部分
黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后微循环的影响
目的:观察黄芪丹参注射液对大鼠骨骼肌钝挫伤后修复过程中局部微循环的影响。
方法:78只雄性SD大鼠随机分为中药治疗组、生理盐水组、自然愈合组和空白对照组4组。前3组采用打击装置造成右侧腓肠肌中段钝挫伤模型,分别于损伤局部注射黄芪丹参注射液、等量生理盐水以及不注射药物。于损伤后2h、24h、72h、120h在体观察腓肠肌的微循环情况。空白对照组为正常大鼠,未经任何处理,同时进行微循环的观察作为对照
结果:与生理盐水组和自然愈合组相比,中药治疗组微动脉直径在第24h、72h明显扩张(P＜0.05),且毛细血管血流量在24h时明显增加(P＜0.05)。与空白对照组相比,各组的湿/干重比(W/D)在2h、24h时明显升高(P＜0.05),但中药治疗组升高程度明显低于生理盐水组和自然愈合组(P＜0.05)。各组间血流动力学无明显差异(P＞0.05)
结论:骨骼肌钝挫伤后早期给予黄芪丹参注射液可明显改善损伤骨骼肌的局部微循环情况,并减轻组织水肿程度,从而达到促进骨骼肌损伤愈合的作用
Skeletal muscle injury presents the most common injury in sports medicine,whose incidence varies from 10%-55%.Skeletal muscle injury presents a challenging problem in sports medicine,as injured muscles heal very slowly and often with scar recovery, which severe influence motor function.It has been observed that injured muscles can initiate regeneration promptly,but the healing process is often inefficient and hindered by the formation of scar tissue,which may contribute to the tendency for muscle injury to recur.It has been reported that skeletal muscle contusion at early can direct trauma to microvessels results in membrane damage,endothelial cell swelling,perivascular hemorrhage,and uncontrolled clot formation.leading to additional local ischemia,in turn,induces further degradation of membrane phospholipids,accumulation of free radicals,and inflammation-induced oxidative stress may aggravate evolving tissue damage,previous experimental studies have shown that maximum posttraumatic microcirculatory disturbances and secondary tissue damage evolve over time and are not observed before 24 hours after contusion.The presence of local microcirculation damage and inflammation reactive in muscle may lead to overproduction of reactive oxygen species.These species may damage lipid membranes and produce cell necrosis, but antioxidant enzymes such as superoxide dismutase,catalase and glutathione peroxidase could reduce oxidative stress and protect skeletal muscle cell.Thus,early restoration local microcirculations,reduce free radicals,elevate antioxidant enzymes activities are becoming a hot research.Our previous experimental studies have shown that Chinese medicine HuangqiDanshen could promote skeletal muscle expression of myosin heavy chain,short the healing process of injured muscle and enhance regeneration of injured muscle.However the detailed mechanism underlying beneficial effects of Huangqidanshen on skeletal muscle contusion remain to be established. Therefore,the aims of this experimental study are to asses the effects of HuangqiDanshen on oxidative stress and microcirculation after acute skeletal muscle contusion.
In the part one of our study,we observe the effect of Chinese medicine HuangqiDanshen on oxidative stress in rat skeletal muscles after acute contusion. The present study aimed to investigate the effect of HuangqiDanshen on parameters of oxidative stress,namely lipid peroxidation product malondialdehyde(MDA) and the activities of antioxidant enzymes,catalase(CAT),superoxide dismutase(SOD) and glutathione peroxidase(GSH-px),in skeletal muscle after contusion.Thus,to establish whether use of HuangqiDanshen could scavenge free radical,elevate antioxidant enzymes activities in the process of skeletal muscle after contusion.
In the part two of our study,we observe the effect of Chinese medicine HuangqiDanshen on microcirculation in rat skeletal muscles after acute contusion. This study quantitatively analyzed the change of blood hemodynamics,the edema index of skeletal muscle,the changes of arteriolar internal diameter,microvascular flow rate.Therefore,to observe whether administration HuangqiDanshen could amelioration microcirculation injury,attenuate tissue edema,and promote the healing progress of the contused skeletal muscle.
Part One Effects of Chinese Medicine HuangqiDanshen on Oxidative Stress in Rat Skeletal Muscles after Acute Contusion
Objective To investigate the effects of Chinese medicine HuangqiDanshen on oxidative stress in rat skeletal muscles after acute contusion..
Methods Seventy two male Sprague-Dawley rats were randomly divided into three groups(24 rats each group):(1) Chinese medicine HuangqiDanshen group;(2) physiological saline group;(3) natural healing group.The muscle contusion was produced at the gastrocnemius by specific device;Local injection by Chinese medicine HuangqiDanshen at injured site;group physiological saline treated with the injection of physiological saline,and group natural healing for control.The remaining six rats were used as normal control.The muscles were sampled at the day 1,4,7 and 14 after injury respectively,and then investigated the parameters of oxidative stress,namely MDA and the activities of antioxidant enzymes(CAT,SOD and GSH-px) in gastrocnemius after contusion..
Result Compared with the physiological saline group and natural healing group,SOD and GSH-px activities in Chinese medicine group were significantly increase after contusion(P＜0.05).However,the CAT activity had no change(P＞0.05).The concentrations of MDA in Chinese medicine group were lower than that of physiological saline group and natural healing group at days 4,7 after injury(P＜0.05)
Conclusion The Chinese medicine HuangqiDanshen could significantly reduce the content of oxidative product MDA,protect the skeletal muscles in the healing process from oxidative injury and markedly increase the reducing enzyme SOD,GSH-px activities of contused skeletal muscle.
Part Two Effects of Chinese Medicine HuangqiDanshen on Microcirculation in Rat Skeletal Muscles after Acute Contusion
Objective To investigate the effects of Chinese medicine HuangqiDanshen on microcirculation in rat skeletal muscles after acute contusion.
Methods Seventy eight male Sprague-Dawley rats were randomly divided into four groups:(1) Chinese medicine treatment group(A);(2) physiological saline group(B); (3) natural healing group(C);(4) control group(D).The acute skeletal muscle contusion model was produced at the right gastrocnemius by specific device.Local injection at the injury site with Chinese medicine HuangqiDanshen in group A;local injection with physiological saline in group B;The group C without intervention at injured site,and the blank group D as control.Microcirculations of gastrocnemius in vivo were observation at 2h,24h,72h and 120h respectively after contusion.Rats that were not injured served as control.
Result Compared with the group B and group C,the internal diameters of arteriole in group A were significantly dilation at 24h and 72h,the blood flows of capillary were markedly increase at 24h after contusion(P＜0.05).Compared with group D,the Wet/ Dry Weight Ratios of each group were significantly increase at 2h and 24h,but edema in group A was less pronounced compared with group B or group C.The hemodynamics,however,have no significantly changed in each group(P＞0.05).
Conclusions Administration Chinese medicine HuangqiDanshen at early could amelioration microcirculation injury,attenuate tissue edema,and promote the healing process of the contused skeletal muscles.
本实验第一部分研究黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后氧化应激的影响。通过测定骨骼肌钝挫伤以后组织中脂质过氧化产物丙二醛,抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶)的活性来探讨黄芪丹参注射液是否是通过清除自由基,提高抗氧化酶活性从而促进了骨骼肌损伤后的愈合
本实验第二部分研究黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后微循环的影响。通过测定骨骼肌钝挫伤后大鼠全身血流动力学的改变,骨骼肌的湿、干重比值,以及损伤局部微动脉的管径变化,毛细血管流速变化,观察给予黄芪丹参注射液后是否具有改善微循环,减轻水肿从而促进损伤骨骼肌的愈合。
第一部分
黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后氧化应激的影响
目的:观察黄芪丹参注射液对大鼠骨骼肌钝挫伤后修复过程中氧化应激的影响
方法:72只雄性SD大鼠随机分为中药治疗组、生理盐水组、自然愈合组,每组24只。采用打击装置造成右侧腓肠肌中段钝挫伤模型,分别于损伤局部注射黄芪丹参注射液、生理盐水、不作处理。另6只做空白对照(未经任何处理)。于损伤后1、4、7和14天取腓肠肌测定丙二醛(MDA)含量、过氧化氢酶(CAT)活性、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-px)活性。
结果:与生理盐水组和自然愈合组相比,中药组腓肠肌SOD、GSH-px的活性在1、4、7天明显升高(P＜0.05),而CAT活性则无明显变化(P＞0.05)。中药组腓肠肌MDA含量在伤后4、7天明显低于生理盐水组和自然愈合组(P＜0.05)。
结论:黄芪丹参注射液可明显减少氧化产物MDA含量,减轻骨骼肌钝挫伤愈合过程中的氧化性损伤,并显著提高骨骼肌还原酶SOD和GSH-px的活性。
第二部分
黄芪丹参注射液对大鼠急性骨骼肌钝挫伤后微循环的影响
目的:观察黄芪丹参注射液对大鼠骨骼肌钝挫伤后修复过程中局部微循环的影响。
方法:78只雄性SD大鼠随机分为中药治疗组、生理盐水组、自然愈合组和空白对照组4组。前3组采用打击装置造成右侧腓肠肌中段钝挫伤模型,分别于损伤局部注射黄芪丹参注射液、等量生理盐水以及不注射药物。于损伤后2h、24h、72h、120h在体观察腓肠肌的微循环情况。空白对照组为正常大鼠,未经任何处理,同时进行微循环的观察作为对照
结果:与生理盐水组和自然愈合组相比,中药治疗组微动脉直径在第24h、72h明显扩张(P＜0.05),且毛细血管血流量在24h时明显增加(P＜0.05)。与空白对照组相比,各组的湿/干重比(W/D)在2h、24h时明显升高(P＜0.05),但中药治疗组升高程度明显低于生理盐水组和自然愈合组(P＜0.05)。各组间血流动力学无明显差异(P＞0.05)
结论:骨骼肌钝挫伤后早期给予黄芪丹参注射液可明显改善损伤骨骼肌的局部微循环情况,并减轻组织水肿程度,从而达到促进骨骼肌损伤愈合的作用
Skeletal muscle injury presents the most common injury in sports medicine,whose incidence varies from 10%-55%.Skeletal muscle injury presents a challenging problem in sports medicine,as injured muscles heal very slowly and often with scar recovery, which severe influence motor function.It has been observed that injured muscles can initiate regeneration promptly,but the healing process is often inefficient and hindered by the formation of scar tissue,which may contribute to the tendency for muscle injury to recur.It has been reported that skeletal muscle contusion at early can direct trauma to microvessels results in membrane damage,endothelial cell swelling,perivascular hemorrhage,and uncontrolled clot formation.leading to additional local ischemia,in turn,induces further degradation of membrane phospholipids,accumulation of free radicals,and inflammation-induced oxidative stress may aggravate evolving tissue damage,previous experimental studies have shown that maximum posttraumatic microcirculatory disturbances and secondary tissue damage evolve over time and are not observed before 24 hours after contusion.The presence of local microcirculation damage and inflammation reactive in muscle may lead to overproduction of reactive oxygen species.These species may damage lipid membranes and produce cell necrosis, but antioxidant enzymes such as superoxide dismutase,catalase and glutathione peroxidase could reduce oxidative stress and protect skeletal muscle cell.Thus,early restoration local microcirculations,reduce free radicals,elevate antioxidant enzymes activities are becoming a hot research.Our previous experimental studies have shown that Chinese medicine HuangqiDanshen could promote skeletal muscle expression of myosin heavy chain,short the healing process of injured muscle and enhance regeneration of injured muscle.However the detailed mechanism underlying beneficial effects of Huangqidanshen on skeletal muscle contusion remain to be established. Therefore,the aims of this experimental study are to asses the effects of HuangqiDanshen on oxidative stress and microcirculation after acute skeletal muscle contusion.
In the part one of our study,we observe the effect of Chinese medicine HuangqiDanshen on oxidative stress in rat skeletal muscles after acute contusion. The present study aimed to investigate the effect of HuangqiDanshen on parameters of oxidative stress,namely lipid peroxidation product malondialdehyde(MDA) and the activities of antioxidant enzymes,catalase(CAT),superoxide dismutase(SOD) and glutathione peroxidase(GSH-px),in skeletal muscle after contusion.Thus,to establish whether use of HuangqiDanshen could scavenge free radical,elevate antioxidant enzymes activities in the process of skeletal muscle after contusion.
In the part two of our study,we observe the effect of Chinese medicine HuangqiDanshen on microcirculation in rat skeletal muscles after acute contusion. This study quantitatively analyzed the change of blood hemodynamics,the edema index of skeletal muscle,the changes of arteriolar internal diameter,microvascular flow rate.Therefore,to observe whether administration HuangqiDanshen could amelioration microcirculation injury,attenuate tissue edema,and promote the healing progress of the contused skeletal muscle.
Part One Effects of Chinese Medicine HuangqiDanshen on Oxidative Stress in Rat Skeletal Muscles after Acute Contusion
Objective To investigate the effects of Chinese medicine HuangqiDanshen on oxidative stress in rat skeletal muscles after acute contusion..
Methods Seventy two male Sprague-Dawley rats were randomly divided into three groups(24 rats each group):(1) Chinese medicine HuangqiDanshen group;(2) physiological saline group;(3) natural healing group.The muscle contusion was produced at the gastrocnemius by specific device;Local injection by Chinese medicine HuangqiDanshen at injured site;group physiological saline treated with the injection of physiological saline,and group natural healing for control.The remaining six rats were used as normal control.The muscles were sampled at the day 1,4,7 and 14 after injury respectively,and then investigated the parameters of oxidative stress,namely MDA and the activities of antioxidant enzymes(CAT,SOD and GSH-px) in gastrocnemius after contusion..
Result Compared with the physiological saline group and natural healing group,SOD and GSH-px activities in Chinese medicine group were significantly increase after contusion(P＜0.05).However,the CAT activity had no change(P＞0.05).The concentrations of MDA in Chinese medicine group were lower than that of physiological saline group and natural healing group at days 4,7 after injury(P＜0.05)
Conclusion The Chinese medicine HuangqiDanshen could significantly reduce the content of oxidative product MDA,protect the skeletal muscles in the healing process from oxidative injury and markedly increase the reducing enzyme SOD,GSH-px activities of contused skeletal muscle.
Part Two Effects of Chinese Medicine HuangqiDanshen on Microcirculation in Rat Skeletal Muscles after Acute Contusion
Objective To investigate the effects of Chinese medicine HuangqiDanshen on microcirculation in rat skeletal muscles after acute contusion.
Methods Seventy eight male Sprague-Dawley rats were randomly divided into four groups:(1) Chinese medicine treatment group(A);(2) physiological saline group(B); (3) natural healing group(C);(4) control group(D).The acute skeletal muscle contusion model was produced at the right gastrocnemius by specific device.Local injection at the injury site with Chinese medicine HuangqiDanshen in group A;local injection with physiological saline in group B;The group C without intervention at injured site,and the blank group D as control.Microcirculations of gastrocnemius in vivo were observation at 2h,24h,72h and 120h respectively after contusion.Rats that were not injured served as control.
Result Compared with the group B and group C,the internal diameters of arteriole in group A were significantly dilation at 24h and 72h,the blood flows of capillary were markedly increase at 24h after contusion(P＜0.05).Compared with group D,the Wet/ Dry Weight Ratios of each group were significantly increase at 2h and 24h,but edema in group A was less pronounced compared with group B or group C.The hemodynamics,however,have no significantly changed in each group(P＞0.05).
Conclusions Administration Chinese medicine HuangqiDanshen at early could amelioration microcirculation injury,attenuate tissue edema,and promote the healing process of the contused skeletal muscles.
引文
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16.刘克敏,刘振玉.黄芪的药理作用及其在运动医学中的应用.现代中西医结合杂志,2005,14(17):2346-2347.
17.Halliwell B.Free radicals and antioxidants:a personal view.Nutr Rev,1994,52(8):253-265.
18.李国珍,王生,冯鑫.维生素C对大鼠肌肉拉伤所致过氧化损伤的保护作用.中华劳动卫生职业病杂志,2004,22(4):283-285.
19.Menth-Chiari WA,Curl WW,Rosencrance E,et al.Contusion of skeletal muscle increasesleukocyte-endothelial cell interactions:an intravital microscopic study in rats.J Trauma.1998;45(4):709-714.
20.]Menger MD,Vollmar B.Adhesion molecules as determinants of disease:from molecular biology to surgical research.Br J Surg 1996,83(5):588-601.
21.Rot A,Hub E,Middleton J,et al.Some aspects of IL-8pathophysiology.111:Chemokine interaction with endothelial cells.J Leukocyte Biol.1996,59(1):39-44.
22.DeaI,DN,Tipton J,Rosencrance E,et al.Ice reduces edema.A study of microvascular permeability in rats J.Bone Joint Surg..2002,84-A(9):1573-1578
23.鲍翠玉,郑敏,赵骥.黄芪对大运动量训练大鼠内皮功能及心肌超微结构的影响.中国运动医学杂志,2006,25(1):87-89
24.Rubinstein 1,Abassi Z,Coleman R,et al.Involvement of nitric oxide system in experimental muscle crush injury.J Clin lnvesr,1998,101(6):1325-1333.
25.常虹,刘萍.丹参对微循环的影响.中国药物应用与检测,2006,4:21-24
1.Beiner JM,Jokl P.Muscle contusion injuries:current treatment options.J Am Acad Orthop Surg.2001,9(4):227-237.
2.Garrett WE.Muscle strain injuries.Am J Sports Med.1996,24(6):S2-S8.
3.Huard J.Li Y.Fu FH.Muscle injuries and repair:current trends in research.Journal of Bone & Joint Surgery.2002,84-A(5):822-832
4.J(a|¨)rvinen M,Lehto MUK.The effect of early mobilization and immobilization on the healing process following muscle injuries.Sports Med.1993,15(2):78-89.
5.Kujala UM,Orava S,J(a|¨)rvinen M.Hamstring injuries:current trends in treatment and prevention.Sports Med.1997,23(6):397-404.
6.Best TM,McCabe RP,Corr D,et al.Evaluation of a new method to create a standardized muscle stretch injury.Med Sci Sports Exerc.1998,30(2):200-205.
7.Crisco JJ,Hentel KD,Jackson WO,et al.Maximal contraction lessens impact response in a muscle contusion model.J Biomech.1996,29(10):1291-1296.
8.Hurme T,Kalimo H,Lehto M,et al.Healing of skeletal muscle injury:an ultrastructural and immunohistochemical study.Med Sci Sports Exerc.1991,23(7):801-810.
9.McNeil PL.Repairing a torn cell surface:make way,lysosomes to the rescue.J Cell Sci.2002,115(5):873-879.
10.Toumi H,Best TM.The inflammatory response:friend or enemy for muscle injury? Br J Sports Med.2003,37(4):284-286
11.Tiidus PM.Radical species in inflammation and overtraining.Can J Physiol Pharmacol.1998,76(5):533-538.
12.Nguyen HX,Tidball JG.Interactions between neutrophils and macrophages promote macrophage killing of muscle cells in vitro.J Physiol.2003,547(1):125～132.
13.Best TM,Hunter KD.Muscle injury and repair.Phys Med Rehabil Clin N Am.2000,11(2):251～266.
14.Summan M.Warren GL.Mercer RR.et al.Macrophages and skeletal muscle regeneration:a clodronate-containing liposome depletion study.American Journal of Physiology-Regulatory Integrative & Comparative Physiology.2006,290(6):1488～1495.
15.Chazaud B,Sonnet C,Lafuste P,et al.Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth.J Cell Biol.2003,163(5):1133～1143
16.Rak J,Kerbel RS.bFGF and tumor angiogenesis:back in the limelight?Nat Med.1997,3(10):1083～1084.
17.Warren GL,Hulderman T,Jensen N,et al.Physiological role of tumor necrosis factor in traumatic muscle injury.FASEB J.2002,16(12):1630～1632
18.Burkin DJ,Kaufman SJ.The alpha 7 beta 1 integrin in muscle development and disease.Cell Tissue Res.1999,296(1):183～190.
19.Charge SBP,Rudnicki MA.Cellular and molecular regulation of muscle regeneration.Physiol Rev.2004,84(1):209～238.
20.Hurme T,Kalimo H,Lehto M,et al.Healing of skeletal muscle injury:an ultrastructural and immunohistochemical study.Med Sci Sports Exerc.1991,23(7):801-810
21.Hurme T,Kalimo H.Activation of myogenic precursor cells after muscle injury.Med Sci Sports Exerc.1992,24(2):197～205.
22.Qu-Petersen Z,Deasy B,Jankowski R,et al.Identification of a novel population of muscle stem cells in mice:potential for muscle regeneration.J Cell Biol.2002,157(5):851～864.
23.Zammit PS,Golding JP,Nagata Y,et al.Muscle satellite cells adopt divergent fates:a mechanism for self-renewal? J Cell Biol.2004,166(3):347～357
24.Shefer G,Wleklinski-Lee M,Yablonka-Reuveni Z.Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway.J Cell Sci.2004,117(22):5393～5404.
25.Charge SBP,Rudnicki MA.Cellular and molecular regulation of muscle regeneration.Physiol Rev.2004,84(1):209～238.
26.Grounds MD,White JD,Rosenthal N,et al.The role of stem cells in skeletal and cardiac muscle repair.J Histochem Cytochem.2002,50(5):589～610.
27.Dreyfus PA,Chretien F,Chazaud B,et al.Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches.Am J Pathol.2004,164(3):773～779.
28.Relaix F,D Montarras,S Zaffran,et al.Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells.J Cell Biol.2006,172(1):91～102
29.Shi X and DJ Garry.Muscle stem cells in development,regeneration,and disease.Genes Dev.2006,20(13):1692～1708.
30.Vaittinen S,Hurme T,Rantanen J,et al.Transected myofibres may remain permanently divided in two parts.Neuromuscul Disord.2002,12(6):584～587.
31.Cannon JG,St Pierre BA.Cytokines in exertion-induced skeletal muscle injury.Mol Cell Biochem.1998,179(1-2):159～167
32.Li Y,Huard J.Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle.Am J Pathol.2002,161(3):895～907.
33.Goetsch SC,Hawke TJ,Gallardo TD,et al.Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration.Physiol Genomics.2003,14(3):261～271.
34.Wierzbicka-Patynowski I,Schwarzbauer JE.The ins and outs of fibronectin matrix assembly.J Cell Sci.2003,116(16):3269～3276.
35.Jarvinen TAH,Jarvinen TLN,Kannus P,et al.Ectopic expression of tenascin-C.J Cell Sci.2003,116(19):3851～3853.
36.Yan Z,Choi S,Liu X,et al.Highly coordinated gene regulation in mouse skeletal muscle regeneration.J Biol Chem.2003,278(10):8826～8836.
37.Kaariainen M,Kaariainen J,Jarvinen TLN,et al.Correlation between biomechanical and structural changes during the regeneration of skeletal muscle after laceration injury.J Orthop Res.1998,16(2):197～206.
38.Chan YS,Li Y,Foster W,et al.Antifibrotic effects of suramin in injured skeletal muscle after laceration.J Appl Physiol.2003,95(2):771～780.
39.Foster W,Li Y,Usas A,et al.Gamma interferon as an antifibrosis agent in skeletal muscle.J Orthop Res.2003,21(5):798～804.
40.Fukushima K,Badlani N,Usas A,et al.The use of an antifibrosis agent to improve muscle recovery after laceration.Am J Sports Med.2001,29(4):394～402
41.Kaariainen M,Kaariainen J,Jarvinen TLN,et al.Integrin and dystrophin associated adhesion protein complexes during regeneration of shearing-type muscle injury.Neuromuscul Disord.2000,10(2):121～134
42.Kaariainen M,Liljamo T,Pelto-Huikko M,et al.Regulation of alpha7 integrin by mechanical stress during skeletal muscle regeneration.Neuromuscul Disord.2001,11(4):360～369
43.Rantanen J,Ranne J,Hurme T,et al.Denervated segments of injured skeletal muscle fibres are reinnervated by newly formed neuromuscular junctions.J Neuropathol Exp Neurol.1995,54(2):188～194
2.Hurme T,Kalimo H,Sandberg M,et al.Localization of typeⅠand Ⅲcollagen and fibronectin production in injured gastrocnemius muscle.Lab Invest.1991;64(1):76-84.
3.Kasemkijwattana C,Menetrey J,Somogyl G;et al.Development of approaches to improve the healing fowllowing muscle contusion.Cell Transplant.1998;7(6):585-598.
4.Huard J,Li Y,Fu FH.Muscle injuries and repair:current trends in research.J Bone Joint Surg Am Volume.2002;84-A(5):822-832.
5.Tiidus PM.Radical species in inflammation and overtraining.Can J Physiol Pharmacol.1998,76(5):533-538
6.朱文辉,陈世益,任惠民,等.活血生肌类中药对大鼠急性钝挫伤后骨骼肌Ⅱb型MHC及Ⅰ、Ⅲ型胶原蛋白表达的影响.中国运动医学杂志,2005,24(2):182-186.
7.陈世益,李云霞,陈疾忤,等.中药黄芪、丹参注射液治疗运动员骨骼肌损伤多中心临床研究.中国运动医学杂志,2008,27(4):468-469.
8.Kami K,Masuhara M,Kashiba H,et al.Changes of vinculin and extracellular matrix components following blunt trauma to rat skeletal muscle.Med Sci Sports Exerc,1993,25(7):832-840.
9.Huard J,Li Y,Fu FH.Muscle injuries and repair:current trends in research.J Bone Joint Surg,2002,84-A(5):822-832.
10.Toumi H,Best TM.The inflammatory response:friend or enemy for muscle injury? Br J Sports Med,2003,37(4):284-286.
11.Nikolaidis MG.Paschalis V.Giakas G.et al.Decreased blood oxidative stress after repeated muscle-damaging exercise.Med Sci Sports Exerc,2007,39(7):1080-1089.
12.黄修涛,方宏秀.复方黄芪注射液对培养大鼠乳鼠心肌细胞缺糖缺氧/复糖复氧损伤的保护作用.中国中医药科技,1999,6(4):229-230.
13.Yu BP.Cellular defenses against damage from reactive oxygen species.Physiol Rev,1994,74(1):139-162.
14.Duthie GG,Robertson JD,Maughan RJ,et al.Blood antioxidant status and erythrocyte lipid peroxidation following distance running.Arch Biochem Biophys,1990,282(1):78-83.
15.祁莉萍,汪太平,史学功,等.丹参注射液对稳定型心绞痛患者抗氧化作用的研究.安徽医科大学学报,2001,36(4):287-289.
16.刘克敏,刘振玉.黄芪的药理作用及其在运动医学中的应用.现代中西医结合杂志,2005,14(17):2346-2347.
17.Halliwell B.Free radicals and antioxidants:a personal view.Nutr Rev,1994,52(8):253-265.
18.李国珍,王生,冯鑫.维生素C对大鼠肌肉拉伤所致过氧化损伤的保护作用.中华劳动卫生职业病杂志,2004,22(4):283-285.
19.Menth-Chiari WA,Curl WW,Rosencrance E,et al.Contusion of skeletal muscle increasesleukocyte-endothelial cell interactions:an intravital microscopic study in rats.J Trauma.1998;45(4):709-714.
20.]Menger MD,Vollmar B.Adhesion molecules as determinants of disease:from molecular biology to surgical research.Br J Surg 1996,83(5):588-601.
21.Rot A,Hub E,Middleton J,et al.Some aspects of IL-8pathophysiology.111:Chemokine interaction with endothelial cells.J Leukocyte Biol.1996,59(1):39-44.
22.DeaI,DN,Tipton J,Rosencrance E,et al.Ice reduces edema.A study of microvascular permeability in rats J.Bone Joint Surg..2002,84-A(9):1573-1578
23.鲍翠玉,郑敏,赵骥.黄芪对大运动量训练大鼠内皮功能及心肌超微结构的影响.中国运动医学杂志,2006,25(1):87-89
24.Rubinstein 1,Abassi Z,Coleman R,et al.Involvement of nitric oxide system in experimental muscle crush injury.J Clin lnvesr,1998,101(6):1325-1333.
25.常虹,刘萍.丹参对微循环的影响.中国药物应用与检测,2006,4:21-24
1.Beiner JM,Jokl P.Muscle contusion injuries:current treatment options.J Am Acad Orthop Surg.2001,9(4):227-237.
2.Garrett WE.Muscle strain injuries.Am J Sports Med.1996,24(6):S2-S8.
3.Huard J.Li Y.Fu FH.Muscle injuries and repair:current trends in research.Journal of Bone & Joint Surgery.2002,84-A(5):822-832
4.J(a|¨)rvinen M,Lehto MUK.The effect of early mobilization and immobilization on the healing process following muscle injuries.Sports Med.1993,15(2):78-89.
5.Kujala UM,Orava S,J(a|¨)rvinen M.Hamstring injuries:current trends in treatment and prevention.Sports Med.1997,23(6):397-404.
6.Best TM,McCabe RP,Corr D,et al.Evaluation of a new method to create a standardized muscle stretch injury.Med Sci Sports Exerc.1998,30(2):200-205.
7.Crisco JJ,Hentel KD,Jackson WO,et al.Maximal contraction lessens impact response in a muscle contusion model.J Biomech.1996,29(10):1291-1296.
8.Hurme T,Kalimo H,Lehto M,et al.Healing of skeletal muscle injury:an ultrastructural and immunohistochemical study.Med Sci Sports Exerc.1991,23(7):801-810.
9.McNeil PL.Repairing a torn cell surface:make way,lysosomes to the rescue.J Cell Sci.2002,115(5):873-879.
10.Toumi H,Best TM.The inflammatory response:friend or enemy for muscle injury? Br J Sports Med.2003,37(4):284-286
11.Tiidus PM.Radical species in inflammation and overtraining.Can J Physiol Pharmacol.1998,76(5):533-538.
12.Nguyen HX,Tidball JG.Interactions between neutrophils and macrophages promote macrophage killing of muscle cells in vitro.J Physiol.2003,547(1):125～132.
13.Best TM,Hunter KD.Muscle injury and repair.Phys Med Rehabil Clin N Am.2000,11(2):251～266.
14.Summan M.Warren GL.Mercer RR.et al.Macrophages and skeletal muscle regeneration:a clodronate-containing liposome depletion study.American Journal of Physiology-Regulatory Integrative & Comparative Physiology.2006,290(6):1488～1495.
15.Chazaud B,Sonnet C,Lafuste P,et al.Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth.J Cell Biol.2003,163(5):1133～1143
16.Rak J,Kerbel RS.bFGF and tumor angiogenesis:back in the limelight?Nat Med.1997,3(10):1083～1084.
17.Warren GL,Hulderman T,Jensen N,et al.Physiological role of tumor necrosis factor in traumatic muscle injury.FASEB J.2002,16(12):1630～1632
18.Burkin DJ,Kaufman SJ.The alpha 7 beta 1 integrin in muscle development and disease.Cell Tissue Res.1999,296(1):183～190.
19.Charge SBP,Rudnicki MA.Cellular and molecular regulation of muscle regeneration.Physiol Rev.2004,84(1):209～238.
20.Hurme T,Kalimo H,Lehto M,et al.Healing of skeletal muscle injury:an ultrastructural and immunohistochemical study.Med Sci Sports Exerc.1991,23(7):801-810
21.Hurme T,Kalimo H.Activation of myogenic precursor cells after muscle injury.Med Sci Sports Exerc.1992,24(2):197～205.
22.Qu-Petersen Z,Deasy B,Jankowski R,et al.Identification of a novel population of muscle stem cells in mice:potential for muscle regeneration.J Cell Biol.2002,157(5):851～864.
23.Zammit PS,Golding JP,Nagata Y,et al.Muscle satellite cells adopt divergent fates:a mechanism for self-renewal? J Cell Biol.2004,166(3):347～357
24.Shefer G,Wleklinski-Lee M,Yablonka-Reuveni Z.Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway.J Cell Sci.2004,117(22):5393～5404.
25.Charge SBP,Rudnicki MA.Cellular and molecular regulation of muscle regeneration.Physiol Rev.2004,84(1):209～238.
26.Grounds MD,White JD,Rosenthal N,et al.The role of stem cells in skeletal and cardiac muscle repair.J Histochem Cytochem.2002,50(5):589～610.
27.Dreyfus PA,Chretien F,Chazaud B,et al.Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches.Am J Pathol.2004,164(3):773～779.
28.Relaix F,D Montarras,S Zaffran,et al.Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells.J Cell Biol.2006,172(1):91～102
29.Shi X and DJ Garry.Muscle stem cells in development,regeneration,and disease.Genes Dev.2006,20(13):1692～1708.
30.Vaittinen S,Hurme T,Rantanen J,et al.Transected myofibres may remain permanently divided in two parts.Neuromuscul Disord.2002,12(6):584～587.
31.Cannon JG,St Pierre BA.Cytokines in exertion-induced skeletal muscle injury.Mol Cell Biochem.1998,179(1-2):159～167
32.Li Y,Huard J.Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle.Am J Pathol.2002,161(3):895～907.
33.Goetsch SC,Hawke TJ,Gallardo TD,et al.Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration.Physiol Genomics.2003,14(3):261～271.
34.Wierzbicka-Patynowski I,Schwarzbauer JE.The ins and outs of fibronectin matrix assembly.J Cell Sci.2003,116(16):3269～3276.
35.Jarvinen TAH,Jarvinen TLN,Kannus P,et al.Ectopic expression of tenascin-C.J Cell Sci.2003,116(19):3851～3853.
36.Yan Z,Choi S,Liu X,et al.Highly coordinated gene regulation in mouse skeletal muscle regeneration.J Biol Chem.2003,278(10):8826～8836.
37.Kaariainen M,Kaariainen J,Jarvinen TLN,et al.Correlation between biomechanical and structural changes during the regeneration of skeletal muscle after laceration injury.J Orthop Res.1998,16(2):197～206.
38.Chan YS,Li Y,Foster W,et al.Antifibrotic effects of suramin in injured skeletal muscle after laceration.J Appl Physiol.2003,95(2):771～780.
39.Foster W,Li Y,Usas A,et al.Gamma interferon as an antifibrosis agent in skeletal muscle.J Orthop Res.2003,21(5):798～804.
40.Fukushima K,Badlani N,Usas A,et al.The use of an antifibrosis agent to improve muscle recovery after laceration.Am J Sports Med.2001,29(4):394～402
41.Kaariainen M,Kaariainen J,Jarvinen TLN,et al.Integrin and dystrophin associated adhesion protein complexes during regeneration of shearing-type muscle injury.Neuromuscul Disord.2000,10(2):121～134
42.Kaariainen M,Liljamo T,Pelto-Huikko M,et al.Regulation of alpha7 integrin by mechanical stress during skeletal muscle regeneration.Neuromuscul Disord.2001,11(4):360～369
43.Rantanen J,Ranne J,Hurme T,et al.Denervated segments of injured skeletal muscle fibres are reinnervated by newly formed neuromuscular junctions.J Neuropathol Exp Neurol.1995,54(2):188～194