神经提取液对失神经肌肉的保护作用

目的：研究神经提取液对失神经肌肉的保护作用。方法：将坐骨神经提取液（ＳＥ）与中枢神经提取液（ＣＥ）应用至ＳＤ大鼠失神经趾长伸肌（ＥＤＬ）中，检测其湿重、总蛋白、钙离子浓度、生理学与组织学指标的变化，并对ＳＥ、ＣＥ、失神经肌肉的蛋白成分进行初步分析。结果：ＳＥ与ＣＥ对失神经ＥＤＬ最大强直收缩力（ＰＯ）与强直收缩后动作电位（ＰＴＰ）的降低、舒张期时程（ＲＴ）的延长、肌肉总蛋白与钙离子的下降、肌湿重与肌纤维截面积的减少有保护作用。结论：ＳＥ与ＣＥ对失神经的肌肉具有保护作用。     

坐骨神经提取液对失神经肌肉的作用

将Ｓｐｒａｇｕｅ Ｄａｗｌｅｙ大鼠为模型，观察失神经后的趾长伸肌应用坐骨神经提取液（ＳＥ）后的变化。通过肌肉对生物学指标最大强直收缩张力（ＰＯ），舒张期时程（ＲＴ）及强直收缩后动作电位（ＰＴＰ）的测量，肌湿重及肌纤维截面积（ＣＳＡ）的测量，分析其结果，发现坐骨神经提取液具有减缓失神经肌肉萎缩的作用。     

神经端侧缝合法防治失神经肌肉萎缩的实验研究

目的研究采用周围神经端侧缝合法防治失神经肌肉萎缩的作用。方法取Ｗｉｓｔａｒ雌性大白鼠２８只,分成３组。（１）实验组：切断大鼠左侧腓总神经,将其远断端与外膜已开窗的胫神经行端侧缝合,共２８侧。（２）失神经组：大鼠右侧腓总神经切断后,将两断端翻转固定为失神经对照侧,共１４侧。（３）正常对照组：大鼠右侧腓总神经不作处理,共１４侧。术后７个月,各组取胫前肌称肌湿重,并检测再生神经结构及肌纤维截面积。结果实验组与正常对照组之间,各项数据无显著性差异（Ｐ＞０．０１）。失神经组与实验组及正常对照组之间,其差异有非常显著性意义（Ｐ＜０．０１）。结论实验证实,神经端侧缝合法是防治失神经肌肉萎缩的一种有效方法     

臂丛损伤后神经移位寄养法预防失神经支配肌萎缩的实验研究

目的研究臂丛损伤后神经移位端侧缝合寄养法是否有预防失神经支配骨骼肌肌萎缩的作用。方法64只SD大鼠随机分成两组。对照组：切断肌皮神经，造成肱二头肌失神经支配。实验组：切断肌皮神经后，胸内侧神经分支移位与肌皮神经远端作端侧缝合寄养失神经支配的肱二头肌。术后2、4、6、8周观察大鼠的行为变化与肱二头肌的萎缩程度，检测肱二头肌肌肉纤颤电位或再生电位、肱二头肌肌肉湿重、肌纤维截面积和Na-K-ATP酶活性。以左侧为实验侧，右侧为自身对照侧，将左侧测量值除以右侧测量值，求各观察值恢复率，比较组间各观察值的恢复率。结果术后对照组随着失神经时间延长，肌肉萎缩程度逐渐加重，屈肘功能不能恢复，纤颤电位波幅逐渐下降，肌肉湿重、肌纤维截面积和酶的活性均逐渐下降；而实验组随着神经寄养时间的延长，肌肉萎缩程度逐渐减轻，屈肘功能逐渐恢复，出现再生电位，肌肉湿重、肌纤维截面积逐渐增加，酶活性逐渐升高，虽不及正常组，但明显不同于肌肉萎缩严重的失神经组。结论神经移位端侧缝合寄养法可以有效地预防失神经支配骨骼肌肌萎缩。     

酸性成纤维细胞生长因子预防失神经支配肌运动终板退变及肌萎缩的实验研究

目的 本研究旨在探讨运动神经损伤后运动终板退变及肌萎缩的预防方法。方法 SD大鼠40只，随机分成5组。处理组切断右侧腓总神经，修复或不修复神经，酸性成纤维细胞生长因子（aFGF）纤维蛋白凝胶载体植入失神经支配的胫前肌神经区周围的肌间隙，设立对照，6周后采用形态学检查进行评价。结果采用aFGF纤维蛋白凝胶载体组，神经修复或未予修复其运动终板结构基本正常，肌肉无明显萎缩；对照组运动终板明显退变或消失，肌肉明显萎缩。结论aFGF纤维蛋白凝胶载体可以有效保护失神经支配肌运动终板，防止肌肉萎缩。     

失神经支配红白肌感觉神经营养活性研究

目的　探讨对失神经支配红、白肌肉内神经生长因子 (NGF)变化规律及 NGF含量与感觉神经营养活性的关系。方法　剪断大鼠坐骨神经制成腓肠肌和比目鱼肌失神经支配模型 ,分别于神经损伤后 1、3、7和 14天取材 ,运用免疫组织化学方法检测失神经支配红、白肌肉内 NGF含量 ,同时用鸡胚背根神经节培养方法测定失神经支配肌肉提取液感觉神经营养活性。结果　腓肠肌和比目鱼肌失神经支配后其 NGF含量均下降 ,两种肌肉组比较无统计学意义(P>0 .0 5 ) ,组内比较以比目鱼肌组下降明显 ;但两种失神经支配肌肉提取液感觉神经营养活性未降低 ,在伤后 7天时反高于对照组 ,两种肌肉组间比较无差异。结论　周围神经损伤会引起其相应支配靶器官 -肌肉组织内 NGF的含量发生变化 ,且具有时间性 ,但红、白肌肉内 NGF含量的变化不一致 ;失神经支配肌肉的神经营养活性是各种营养因子的共同作用结果 ,不能用单一某种神经营养因子来代表     

大鼠骨骼肌异位移植寄养后运动神经植入的电生理研究

目的探讨大鼠骨骼肌异位移植寄养后运动神经植入促进神经再生的作用。方法取鼠龄8个月的健康雄性SD大鼠60只，随机均分为三组：即对照组、原位再植组及异位移植寄养组。对照组：切断支配右侧股薄肌的闭孔神经，造成肌肉失神经支配；原位再植组；切取右侧股薄肌，再回植于原位，闭孔神经植入肌肉；异位移植寄养组：切取右侧股薄肌，移植寄养于左侧股部，闭孔神经植入肌肉。术后25周，采用神经肌电图仪收集各组的神经电生理信息，观察股薄肌大体形态并测量肌湿重。结果对照组股薄肌呈失神经电位；异位移植寄养组和原位再植组相比，神经肌肉电位潜伏期、波幅和神经传导速度差异均无统计学意义（P〉0、05）。对照组股薄肌萎缩明显，肌湿重为158．0±19．3mg；异位移植寄养组与原位再植组股薄肌萎缩不明显，肌湿重分别为509．6±14．5mg和516．8±12．7mg，二者差异无统计学意义（P〉0．05），但均大于对照组，且差异有统计学意义（P〈0．05）。结论运动神经植入能有效防止或减轻异位移植寄养的骨骼肌失神经性萎缩，有助于恢复神经、肌肉的部分功能。     

用纤颤电位波幅衡量失神经肌肉萎缩程度的临床研究

目的研究失神经支配肱二头肌纤颤电位波幅的变化规律，并探索其与肌肉萎缩程度的关系。方法１９９５年８月～１９９６年１２月，检测１７３块因臂丛神经损伤致完全失神经支配的肱二头肌纤颤电位并计算其波幅；６３例在检测同一部位取肌组织送病理检查。被检肌肉行ＡＴＰ酶染色，测定Ｉ、Ｉ型肌纤维面积。结果纤颤电位的波幅和肌纤维的横断面积与失神经时间呈负相关；失神经后第５、６个月及１年以后为纤颤电位波幅的显著下降期；失神经后第４个月为肌纤维的显著萎缩期。纤颤电位的波幅与肌纤维的横截面积呈正相关；男性纤颤电位的波幅及ＩＩ型肌纤维面积均较女性为高（Ｐ＜０．０５）。结论纤颤电位波幅与肌纤维萎缩状态相一致，可作为评估肌肉萎缩程度的定量指标     

肘部尺神经卡压的定位诊断和电生理学研究

目的：对肘部尺神经卡压进行精确定位和电生理学研究。方法：对４６例临床诊断为肘部尺神经卡压患者，除进行常规ＥＭＧ、ＮＣＶ、和尺神经混合神经动作电位（ＭＮＡＰ）测定以外，还进行尺神经短段传导时间（ｓｈｏｒｔｓｅｇｍｅｎｔｃｏｎｄｕｃｔｉｏｎｔｉｍｅ，ＳＳＣＴ）测定。结果：４６例经ＳＳＣＴ测定，发现了卡压最常发生的４个部位，即肱骨内上髁后神经沟、肱尺弓、尺侧腕屈肌的出口和内侧肌间隔。结论：和传统的电生理测定方法相比较，ＳＳＣＴ技术可以更精确地对尺神经卡压进行定位诊断     

骨骼肌失神经和再神经化时肌卫星细胞的变化

目的探讨骨骼肌失神经和再神经化时肌卫星细胞的变化规律，了解肌肉相应形态功能变化的细胞学机制。方法取1月龄Wistar大鼠27只制成失神经肌萎缩模型，于术后1～6个月，逐月取3只大鼠双侧小腿三头肌行组织学、组织化学等形态学检测；同时于术后1、2、3周和1～6个月逐月各取1只大鼠双侧小腿三头肌行细胞生物学检查。取1月龄Wistar大鼠35只制成神经再生模型，分别于失神经即时、术后1～6个月逐月取5只大鼠行神经植入手术，动态观察电生理指标变化至植入术后8周，然后进行形态学指标检测。结果骨骼肌失神经组显示肌湿重、肌细胞截面积迅速减少，胶原纤维含量逐渐增加，失神经后3～4个月DNA增殖期核所占百分比最高，后迅速减少，肌卫星细胞失神经3周数量开始明显增加，但2个月后急剧下降，至4个月时含量已极低。神经再生组神经植入后4～5周可引出肌诱发动作电位，以萎缩2～3个月后神经植入再生效果好，此时肌卫星细胞的分化能力较强。结论骨骼肌失神经支配4个月后卫星细胞数量极少导致肌肉进入萎缩的不可逆期；当失神经2～3个月时再神经化，增殖能力活跃的肌卫星细胞促使此时的萎缩肌功能恢复较好。     

Blockade of L-selectin attenuates reperfusion injury in a rat model

Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus (EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.     

Insulin growth factor-1 decreases muscle atrophy following denervation

Despite modern microsurgical techniques for nerve repair, functional outcome following proximal injury is often unsatisfactory because irreversible muscle atrophy may develop before reinnervation occurs. Because insulin growth factor-1 (IGF-1) has been shown to improve muscle regeneration after injury, and may have a role in muscle preservation following denervation, the purpose of this investigation was to evaluate the histological, immunohistochemical, and electrophysiological differences between normal, denervated, and IGF-1-injected denervated muscle over an 8-week period. Denervated mice gastrocnemius muscles demonstrated a decrease in muscle weight, a decrease in myofiber diameter, an absence of muscle regeneration, an early increase in the number of neuromuscular junctions (NMJs), and a decrease in fast-twitch and maximum tetanic strength as compared to normal muscle up to 8 weeks following denervation. IGF-1-injected denervated muscle, on the other hand, sustained muscle diameter and muscle weight, maintained a smaller number of NMJs, and relatively sustained fast-twitch and maximum tetanic strength as compared to normal muscle over 8 weeks. These data suggest that IGF-1 may help prevent muscle atrophy and secondary functional compromise after denervation.     

细胞外ATP防治失神经肌肉萎缩的实验研究

目的　探索细胞外ATP是否对失神经支配肌肉有保护作用。方法　SD大鼠 12只 ,在梨状肌下缘切断坐骨神经 ,制作腓肠肌失神经支配模型。左侧为实验组 ,术后于腓肠肌内注射ATP 0 .1mg/d ;右侧为对照组 ,腓肠肌内注射等量生理盐水。于术后 8、12周取 2组标本称肌湿重 ,检测运动终板、肌纤维横截面积及组织学变化。结果　实验侧的腓肠肌饱满有弹性、色泽好 ;对照侧肌纤维萎缩变细、色泽苍白。实验组运动终板边缘清晰 ,终板乙酰胆碱酯酶染色较深。比较两组的运动终板平均灰度值和平均光密度值 ,差异有显著性意义 (t =3 .0 5 7、4.13 8,P <0 .0 5 ) ,两组肌纤维横截面积相比 ,差异有显著性意义(t =4.191,P <0 .0 5 )。结论　ATP具有明显延缓失神经肌肉肌萎缩和减轻皮肤溃疡的作用     

Growth factor may decrease muscle atrophy secondary to denervation

Despite modern microsurgical techniques, functional outcomes following brachial-plexus reconstruction and peripheral-nerve repair are usually unsatisfactory, because irreversible muscle atrophy develops before reinnervation occurs. Insulin growth factor-1 (IGF-1) has been shown to improve muscle regeneration after injury, and may have a role in muscle preservation following denervation. This study evaluated the histologic, immunohistochemical, and electrophysiologic differences between normal and denervated muscle over an 8-week time period, and also evaluated the effects of injecting IGF-1 into denervated muscle. Denervated mice gastrocnemius muscles demonstrated a decrease in muscle diameter, a decrease in muscle weight, early nuclear proliferation, and a decrease in fast twitch and maximum tetanic strength, compared to normal gastrocnemius muscle up to 8 weeks following denervation. Four weeks after denervated muscle was injected with IGF-1 at time zero, however, relative preservation of muscle diameter and weight, and maintenance of electrophysiologic contractile properties were observed. These preliminary data suggest that IGF-1 may prevent muscle atrophy secondary to denervation.     

Conservative management of peripheral nerve injuries utilizing selective electrical stimulation of denervated muscle with exponentially progressive - - current forms

One objective of the conservative management of peripheral nerve injuries is to delay and minimize denervation atrophy of the muscle parenchyma. A properly administered program of selective electrical stimulation of denervated muscle may appreciably delay denervation atrophy. Current forms having slowly increasing intensities (exponentially progressive currents) are capable of selective stimulation of denervated muscle while awarding the stimulation of both the innervated muscles and the intact sensory nerves. The present paper discusses the rationale for the utilization of selective electrical stimulation of denervated muscle following peripheral nerve injuries.J Orthop Sports Phys Ther 1985;7(1):11-15.     

An experimental study on denervated muscle atrophy--effect of electrostimulation and comparison with immobilization muscle atrophy

The efficacy of causing muscle atrophy was compared among denervation, arthrodesis and tenotomy in rat anterior tibial muscle. Reduction of wet weight was most pronounced in denervated muscle and least in arthrodesed muscle. Histochemical investigation by ATPase stain revealed that atrophy of Type 1 and Type 2 fiber was more severe in denervated muscle group than in the other two groups. Type 2 fiber atrophy was dominant in denervated muscle and in arthrodesed muscle. Type 1 fiber atrophy was dominant in tenotomized muscle. The effect of electrostimulation on denervated muscle was investigated. Electrostimulation significantly reduced the degree of denervation atrophy. Four weeks after severance of peroneal nerve, tibial nerve-crossing was done and electrostimulation was continued for eight weeks. Recovery of wet weight of re-innervated muscle with electrostimulation was significantly better than that without electrostimulation. Electrostimulation applied to denervated muscle reduced the progress of atrophy and improved the recovery after nerve repair.     

活性氧、线粒体通透性转化孔介导肌细胞凋亡在失神经骨骼肌萎缩中的相关性

目的 观察活性氧(ROS)、线粒体通透性转化孔(MPTP)在失神经骨骼肌萎缩后的表达变化且与肌细胞凋亡的相关性,探讨ROS、MPTP参与失神经骨骼肌萎缩的具体分子机制.方法 将30只Vistar大鼠随机分为对照组、失神经2d组、失神经7d组、失神经14d组、失神经28d组,每组6只.制作坐骨神经切断后失神经支配的腓肠肌Vistar大鼠模型.应用流式细胞术(FCM)检测失神经支配后腓肠肌细胞ROS的含量,激光共聚焦显微镜检测MPTP的开放,脱氧核糖核苷酸转移酶介导的缺口末端标记(TUNEL)法检测肌细胞凋亡.结果 大鼠失神经支配后,肌细胞中的ROS、MPTP及凋亡率与正常对照组比较,表达随失神经支配时间的延长(<28d)而持续增加,且各组的表达均显著高于对照组(P<0.05),ROS的表达与MPTP的开放呈正相关(r=0.884,P<0.01),与肌细胞的凋亡率呈正相关(r=0.893,P<0.01),MPTP的开放与肌细胞凋亡率呈正相关(r=0.927,P<0.01)与肌细胞萎缩指标肌湿重比呈负相关(r=-0.907,P<0.01).结论 ROS、MPTP为调控失神经支配后骨骼肌萎缩的重要分子,其具体机制是通过线粒体介导的凋亡通路促进骨骼肌萎缩.

Abstract：

Objective To study the expression of reactive oxygen species (ROS) and mitochondrial permeability transition pore (MPTP) in denervated skeletal muscle atrophy and its correlation with cell apoptosis, and explore specific molecular mechanism in denervated skeletal muscle atrophy. MethodsThirty Vista rats were randomly divided into five group: control group, 2-days group, 7-days group, 14-days group, 28-days group. Standard model of denervated gastrocnemius muscle was established. The content of ROS and the opening of MPTP in the gastrocnemius were detected by flow cytometry (FCM) and fluorescence microscope respectively. The apoptotic cells in atrophic muscle were examined by TdT-mediated dUTP nick end labeling (TUNEL). Results As compared with the control group, the content of ROS, the opening of MPTP and the apoptosis of gastrocnemius were increased continuously (<28 days) in 2-days group, 7-days group, 14-days group, 28-days group (P<0.05). The content of ROS had a positive correlation with the opening of MPTP (r=0.884,P<0.01) and the apoptosis rate (r=0.893,P<0.01), and the opening of MPTP had a positive correlation with the apoptosis rate (r=0.927,P<0.01), but a negtive correlation with the ratio of muscle wet weight (r=-0.907,P<0.01). Conclusion ROS and MPTP are important elements in regulating skeletal muscle atrophy after denervation by the mitochondrial apoptosis pathway.     

电刺激对失神经支配骨骼肌萎缩的影响

目的 研究电刺激对失神经支配骨骼肌萎缩的影响。方法 选用SD大鼠16只，建立双侧下肢失神经支配胙肠肌的实验模型，电刺激右侧胙肠肌为实验侧，左侧不作电刺激为对照侧，术后2、4周分别观察肌肉的组织学，超微结构，纤颤电位波幅及Na^ -K^ -ATP酶和Ca^2 -ATP酶活性变化。结果 实验侧术后2、4周肢体肌细胞直径及截面积较对照侧下降速度明显减慢；电刺激能延缓肌细胞的线粒体，肌质网退变，但对肌肉纤颤电位波幅无明显影响；实验侧术后2、4周Na^ -K^ -ATP酶活性下降速度比对照侧分别慢15．59％和27．38％；实验侧术后2、4周Ca^2 -ATP酶活性下降速度较对照侧分别慢4．83％和21．64％。结论 电刺激对失神经支配骨骼肌的组织学、电生理及酶组织化学的各项指标均有保护作用，是延缓肌肉萎缩的有效方法。     

Protein abnormality in denervated skeletal muscles from patients with brachial injury

A proteomic analysis was performed to compare protein expression between normal sternocleidomastoid muscle and denervated muscle. Two-dimensional electrophoresis (2-DE) of muscle proteins showed that 26 proteins among about 800 spots in 2-DE gel displayed a decrease and 6 proteins an increase in expression in muscles with denervation atrophy compared to normal controls; the identified proteins that were abnormally expressed could be generally grouped together as metabolic proteins, chaperone proteins, and contractile-apparatus proteins. The significance of these altered proteins is discussed. In particular, the decrease in hD54 may reduce the activity of transmembrane signaling in atrophied muscle, while the disregulation of DnaJC 1 showed a possible role of molecular chaperones in the functional recovery of atrophied muscles.     

一氧化氮合酶抑制剂对失神经肌萎缩的延缓作用

目的 研究一氧化氮合酶（nitric oxide synthase，NOS）竞争性抑制剂L-硝基精氨酸甲酯（N^G-nitro-L-arginine methyl ester，L-NAME）对失神经肌萎缩的延缓作用，为失神经肌萎缩的预防与治疗提供新手段。方法 制备36只成年SD大鼠右下肢腓肠肌失神经支配模型，随机分为L-NAME组（A组）和对照组（B组）。A组：腓肠肌注射L-NAME，于5个不同位点分别注射20μl，总注射剂量为10mg／kg；B组：注射同等体积的生理盐水。于术后2、4和8周测定肌湿重维持率、肌细胞横切面积、肌肉蛋白含量、细胞凋亡数，并观察超微结构的改变。结果术后2、4周A组的肌湿重维持率、肌细胞横切面积、肌肉蛋白含量均明显高于B组，但细胞凋亡数低于B组，差异均有统计学意义（P〈0．05）。超微结构显示，术后2周，肌细胞线粒体、内质网及细胞核改变不明显，两组间无显著性差异；术后4周，A组退变的细胞核较B组少，核质染色均匀。术后8周两组各参数间差异无统计学意义（P〉0．05）。结论 NOS抑制剂L-NAME能在短期内延缓失神经肌萎缩。