周围神经显微减压术联合丹红注射液治疗糖尿病周围神经病变的临床和实验研究
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摘要
糖尿病周围神经病变(Diabetic Peripheral Neuropathy, DPN)是最常见的糖尿病神经系统并发症,致残率高,但缺乏特异性的治疗方法。目前内科治疗DPN的方法以控制血糖、营养神经等对症治疗为主,故特异性、有效性较差,而外科治疗DPN的方法更是乏善可陈。
1988年Dellon率先提出可以应用周围神经减压术治疗DPN,并于1992报道了首批采用周围神经减压术治疗的四肢DPN的病例,疗效优良,从此开启了外科手术治疗DPN的新纪元。
本课题第一部分总结了我科自2004年3月至2012年8月采用周围神经显微减压术治疗的DPN患者42例(50侧),分别阐述了外科诊治DPN的诊断标准、不同部位DPN的临床表现、手术指征的把握、手术方法的选择及术中要点、术后注意事项、有效率、复发率、并发症等。结果显示：①、上肢28例(32侧)术后麻木、疼痛症状缓解率是100%；50%以上的患者手部力弱、运动笨拙症状得到缓解；80%-90%患者手指两点辨别觉恢复正常；术后电生理检测显示100%患者均有改善；术后总的复发率小于7%。②、下肢14例(18侧)患者术后麻木、疼痛症状缓解率为77.7%(14/18),肢体平衡问题术后73.3%(11/15)缓解。所有患者随访5—113个月,平均74个月,随访期间无一例发生顽固性溃疡或截肢。
对于DPN患者术后疗效的评价目前普遍依据患者的主观感受、临床体格检查及神经电生理监测,未来还需要寻求更为科学、客观、准确的指标来进行评估,如观察病变神经的显微结构甚至超微结构等。
本课题第二部分通过采用腹腔注射小剂量链脲佐菌素(Streptozotocin, STZ)的方法制备Ⅰ型糖尿病(Diabetes mellitus, DM)的大鼠模型,持续观察从DM发病到出现DPN的自然过程。DPN大鼠造模成功后,对其足迹步态、神经电生理监测指标、表皮内神经纤维密度以及神经组织病理学检查进行了综合分析,结果显示：腹腔一次性注射60mg/kg剂量的STZ后约8周DPN大鼠动物模型制备成功；模型组与对照组相比：①、足迹步态参数中：后足跟至前足趾之间距离(Print length,PL)、第二足趾至第四足趾之间的距离(Intermediarytoespread, ITS)的测量值的差异具有统计学意义(P<0.05)；②、90%(9/10)DPN大鼠右后肢跗管胫神经入管后较入管前动作电位波幅下降,神经传导速度下降；③、DPN大鼠右后肢外踝上方lcm处表皮内神经纤维数量明显减少、甚至无神经纤维显示,走形更加不规则,更为纤细；④、神经组织严重水肿,髓鞘肿胀明显,局部有空泡变性,轴索水肿,部分轴索分离、变性。
通过以上临床和基础研究可以得出周围神经卡压是DPN的重要致病因素,周围神经显微减压手术正是针对此种病因来确切地治疗DPN,然而针对导致DPN的血管因素和代谢因素的治疗则非手术所及,同时我们在临床实践中发现,部分DPN患者在显微减压术的基础上联合应用丹红注射液(Dan Hong injection, DH)可使症状缓解的更为明显,从而推测DH可以促进病变神经的恢复,因此我们在现有的研究基础之上通过分子生物学实验初步阐明了其直接作用于周围神经雪旺氏细胞(schwann cell, SC)的机理。
本课题第三部分将SC分为正常对照组、加入糖基化终末产物(Advanced Glycation End Products, AGEs)组、DH+AGEs组,培养48h后对同倍视野下SC细胞计数进行SPSS统计分析；在测定SC表达脑源性神经因子(Brain-derived neurotrophic factor, BDNF)的实验中,运用实时定量逆转录聚合酶链反应(real-time RT-PCR)和Western blot技术检测BDNF mRNA和蛋白含量：在测定DH促进SC表达BDNF信号传导通路实验中运用RT-PCR技术对BDNF mRNA进行检测。结果表明：①、DH可直接作用于周围神经的SC细胞；②、DH能明显抑制AGEs导致的SC的凋亡；③、DH能促进SC表达BDNF的mRNA和蛋白；④、PKC及下游的MEK、ERKs和p38蛋白通路可能参与介导了DH促进BDNF mRNA表达的上调。
Diabetic Peripheral Neuropathy is the primary Diabetic Mellitus complication in nervous system.but lacked of effective treatments.Blood surgar level control,neurotrophy intervention and symptomatic treatment may be the main methods from medical,however,specific surgical managements for DPN is less.
In1988,Dellon firstly introduced the surgical treatment for DPN with microsurgical decompression,and then reported the excellent therapeutic efficacy in1992.It became an effective surgical method for DPN from then on.
In part I, retrospectively analysed42(50sides)DPN patients underwent microsurgical decompression from3,2004to8,2012. Diagnostic criteria,clinical manifestation,operative indication,operative methods selection,key points during operation,effective rate and recurrence rate were analysed respectively.Results demonstrated that:①.all the28(32sides)patients alleviated their pain and numbness in upper limbs, more than50%patients improved their hands motor function,80%-90%patients recovered their two point discrimination, electrophysiologic monitoring showed the improvement rate was100%,recurrence rate under7%.②.77.7%patients(14/18sides) released their pain and numbness in lower limbs,73.3%(11/15) cases resolved their balance dysfunction.No one get amputation because of DPN during follow-up period.
Postopertion evaluation at present depends only on patient self felling,physical examination and electrophysiologic monitoring results.So it is necessary to explore more scientific,objective and precise index to judgement operative effection, for example the nervous microstructure,and animal experiment become the first selection.
In prat Ⅱ, we first established the type I diabetic rat models by intraperitoneal injection of STZ (60mg/kg) in male Wistar rats, After successful modeling, the footprint and gait analysis,electrophysiologic examination,nerve fibers density observation in epidermis and right hind tibial nerve tissue staining were performed.Results showing: DPN model preparation time was at least8weeks. Compared with control group:The footprint and gait parameters (PL and ITS) were abnormal in the model group (P<0.05), but there was no significant difference(P>0.05) in TS; The tibial nerve conduction velocity in tarsal tunnel was decreased significantly in the model group (90%rats), compared to0in the control group. The density of nerve fibers of calf epidermal was decreased in the model group. The histopathological examination showed obvious nerve edema,demyelination and axon degeneration.
During clinical practice.we fount that the treatment result was better combined microsurgical decompression with DH compared to single surgical treatment.Therefore.in part Ⅲ, we carried out molecular biology experiment to explore the effective mechanism of DH for peripheral nerve. In SC apoptosis experiment,SC were divided into control group、AGEs group and DH+AGEs group, SPSS was used for statistical analysis of cells number. RT-PCR and western blot was used to detect the BDNF mRNA and protein expression. PKC inhibitor PI3K inhibitor、PKA inhibitor、 MEK inhibitor、ERK inhibitor and p38inhibitor were respectively added into the experiment to determine signaling pathways. The Results demonstrated:SC was decreased significantly in AGEs group than control one (P=0.001),but increased in DH+AGEs group than AGEs group (P=0.0006);DH could promote the expression of BDNF mRNA and protein than control one (P=0.00004); compared to control group, BDNF mRNA expression was decreased in DH+Calphostin C grop (P=0.001); all of the BDNF mRNA expression was significantly decreased in DH+U0126. DH+FR180204and DH+SB203580group(P<0.05). The Conclusion was:DH could effectively inhibit SC apoptosis induced by AGEs and significantly promote BDNF expression; PKC and EK/ERK/p38may be the important signaling transconduction pathway for BDNF expression.
1988年Dellon率先提出可以应用周围神经减压术治疗DPN,并于1992报道了首批采用周围神经减压术治疗的四肢DPN的病例,疗效优良,从此开启了外科手术治疗DPN的新纪元。
本课题第一部分总结了我科自2004年3月至2012年8月采用周围神经显微减压术治疗的DPN患者42例(50侧),分别阐述了外科诊治DPN的诊断标准、不同部位DPN的临床表现、手术指征的把握、手术方法的选择及术中要点、术后注意事项、有效率、复发率、并发症等。结果显示：①、上肢28例(32侧)术后麻木、疼痛症状缓解率是100%；50%以上的患者手部力弱、运动笨拙症状得到缓解；80%-90%患者手指两点辨别觉恢复正常；术后电生理检测显示100%患者均有改善；术后总的复发率小于7%。②、下肢14例(18侧)患者术后麻木、疼痛症状缓解率为77.7%(14/18),肢体平衡问题术后73.3%(11/15)缓解。所有患者随访5—113个月,平均74个月,随访期间无一例发生顽固性溃疡或截肢。
对于DPN患者术后疗效的评价目前普遍依据患者的主观感受、临床体格检查及神经电生理监测,未来还需要寻求更为科学、客观、准确的指标来进行评估,如观察病变神经的显微结构甚至超微结构等。
本课题第二部分通过采用腹腔注射小剂量链脲佐菌素(Streptozotocin, STZ)的方法制备Ⅰ型糖尿病(Diabetes mellitus, DM)的大鼠模型,持续观察从DM发病到出现DPN的自然过程。DPN大鼠造模成功后,对其足迹步态、神经电生理监测指标、表皮内神经纤维密度以及神经组织病理学检查进行了综合分析,结果显示：腹腔一次性注射60mg/kg剂量的STZ后约8周DPN大鼠动物模型制备成功；模型组与对照组相比：①、足迹步态参数中：后足跟至前足趾之间距离(Print length,PL)、第二足趾至第四足趾之间的距离(Intermediarytoespread, ITS)的测量值的差异具有统计学意义(P<0.05)；②、90%(9/10)DPN大鼠右后肢跗管胫神经入管后较入管前动作电位波幅下降,神经传导速度下降；③、DPN大鼠右后肢外踝上方lcm处表皮内神经纤维数量明显减少、甚至无神经纤维显示,走形更加不规则,更为纤细；④、神经组织严重水肿,髓鞘肿胀明显,局部有空泡变性,轴索水肿,部分轴索分离、变性。
通过以上临床和基础研究可以得出周围神经卡压是DPN的重要致病因素,周围神经显微减压手术正是针对此种病因来确切地治疗DPN,然而针对导致DPN的血管因素和代谢因素的治疗则非手术所及,同时我们在临床实践中发现,部分DPN患者在显微减压术的基础上联合应用丹红注射液(Dan Hong injection, DH)可使症状缓解的更为明显,从而推测DH可以促进病变神经的恢复,因此我们在现有的研究基础之上通过分子生物学实验初步阐明了其直接作用于周围神经雪旺氏细胞(schwann cell, SC)的机理。
本课题第三部分将SC分为正常对照组、加入糖基化终末产物(Advanced Glycation End Products, AGEs)组、DH+AGEs组,培养48h后对同倍视野下SC细胞计数进行SPSS统计分析；在测定SC表达脑源性神经因子(Brain-derived neurotrophic factor, BDNF)的实验中,运用实时定量逆转录聚合酶链反应(real-time RT-PCR)和Western blot技术检测BDNF mRNA和蛋白含量：在测定DH促进SC表达BDNF信号传导通路实验中运用RT-PCR技术对BDNF mRNA进行检测。结果表明：①、DH可直接作用于周围神经的SC细胞；②、DH能明显抑制AGEs导致的SC的凋亡；③、DH能促进SC表达BDNF的mRNA和蛋白；④、PKC及下游的MEK、ERKs和p38蛋白通路可能参与介导了DH促进BDNF mRNA表达的上调。
Diabetic Peripheral Neuropathy is the primary Diabetic Mellitus complication in nervous system.but lacked of effective treatments.Blood surgar level control,neurotrophy intervention and symptomatic treatment may be the main methods from medical,however,specific surgical managements for DPN is less.
In1988,Dellon firstly introduced the surgical treatment for DPN with microsurgical decompression,and then reported the excellent therapeutic efficacy in1992.It became an effective surgical method for DPN from then on.
In part I, retrospectively analysed42(50sides)DPN patients underwent microsurgical decompression from3,2004to8,2012. Diagnostic criteria,clinical manifestation,operative indication,operative methods selection,key points during operation,effective rate and recurrence rate were analysed respectively.Results demonstrated that:①.all the28(32sides)patients alleviated their pain and numbness in upper limbs, more than50%patients improved their hands motor function,80%-90%patients recovered their two point discrimination, electrophysiologic monitoring showed the improvement rate was100%,recurrence rate under7%.②.77.7%patients(14/18sides) released their pain and numbness in lower limbs,73.3%(11/15) cases resolved their balance dysfunction.No one get amputation because of DPN during follow-up period.
Postopertion evaluation at present depends only on patient self felling,physical examination and electrophysiologic monitoring results.So it is necessary to explore more scientific,objective and precise index to judgement operative effection, for example the nervous microstructure,and animal experiment become the first selection.
In prat Ⅱ, we first established the type I diabetic rat models by intraperitoneal injection of STZ (60mg/kg) in male Wistar rats, After successful modeling, the footprint and gait analysis,electrophysiologic examination,nerve fibers density observation in epidermis and right hind tibial nerve tissue staining were performed.Results showing: DPN model preparation time was at least8weeks. Compared with control group:The footprint and gait parameters (PL and ITS) were abnormal in the model group (P<0.05), but there was no significant difference(P>0.05) in TS; The tibial nerve conduction velocity in tarsal tunnel was decreased significantly in the model group (90%rats), compared to0in the control group. The density of nerve fibers of calf epidermal was decreased in the model group. The histopathological examination showed obvious nerve edema,demyelination and axon degeneration.
During clinical practice.we fount that the treatment result was better combined microsurgical decompression with DH compared to single surgical treatment.Therefore.in part Ⅲ, we carried out molecular biology experiment to explore the effective mechanism of DH for peripheral nerve. In SC apoptosis experiment,SC were divided into control group、AGEs group and DH+AGEs group, SPSS was used for statistical analysis of cells number. RT-PCR and western blot was used to detect the BDNF mRNA and protein expression. PKC inhibitor PI3K inhibitor、PKA inhibitor、 MEK inhibitor、ERK inhibitor and p38inhibitor were respectively added into the experiment to determine signaling pathways. The Results demonstrated:SC was decreased significantly in AGEs group than control one (P=0.001),but increased in DH+AGEs group than AGEs group (P=0.0006);DH could promote the expression of BDNF mRNA and protein than control one (P=0.00004); compared to control group, BDNF mRNA expression was decreased in DH+Calphostin C grop (P=0.001); all of the BDNF mRNA expression was significantly decreased in DH+U0126. DH+FR180204and DH+SB203580group(P<0.05). The Conclusion was:DH could effectively inhibit SC apoptosis induced by AGEs and significantly promote BDNF expression; PKC and EK/ERK/p38may be the important signaling transconduction pathway for BDNF expression.
引文
1. Yang, W, Lu, J, Weng, J, et al. Prevalence of diabetes among men and women in China[J]. New England Journal of Medicine,2010,362(12):1090-1101.
2.王汉兵,王焱林,欧伟明,等.糖尿病周围神经病变大鼠疼痛模型的建立[J].中国疼痛医学杂志,2007,13(1)：45—46.
3. Ohman CL, Coppey LJ, Gellett JS, et al. Progression of vascularand neuraldysfunctionin sciatic nervesof Zucker diabeticfattyand Zucker rats[J]. AmJPhysiol Endocrinol Metab,2005,289(1):E113-122.
4. Katarzyna Kotulska, Wieslaw Marrcol, Magdalena Larysz-Brysz, et al. Impaired regeneration of Bcl-2 lacking peripheral nerves. Neurological Research,2005,27(12):843-849.
5. Srinivasuwa SM, Ahmad M, Ternandes-Alnermri. Molicular ordering of the Fas-apoptotic pathway:the Fas/APO-1 protease Mch5 is a Crma-inhibitable protease that activates multiple Ced-3/ICE-like cystein protease[J]. Pro. Natl. Acad. Sci. USA,1996,9 (2) 3:14486-14491.
6.Zochodne DW, ChengC. Neurotrophins andothergrowsfactors intheregenerativemilieu ofproximalnerve stumptips Anat.2002; 196:279-228.
7.Xu G, Sima AAF. Altered immediate early gene expression is injured in diabetic nerve:implications in re generation[J].J Neuro pathol Exp Neuro 1,2001,60(10):972-983.
8.Xu G,Murakawa Y, Pierson CR, et al. Altered (i-tubulin and neuro fila-ment expression and impaired axonal gro wth in diabetic nerve regenera-tion[J]. J Neuro path Exp Neuro 1,2002,61(2):164-175.
9. Gordois A, Oglesby A, Scuffham P, et al. The health care costs of diabetic peripheral neuropathy in the U.S. Diabetes Care,2003,26(6):1790-1795. 10. Dellon AL. Optimism in diabetic neuropathy. Ann Plast Surg,1988,20(2): 103-105.
11. Aszmann 0, Tassler PL, Dellon AL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53(6):517-522.
12.任荣.丹红注射液治疗糖尿病周围神经病变的疗效观察[J].中西医结合心脑血管病杂志,2008,6(12)：1489-1499.
13.陈济洲,赵健雄,乔成栋.丹红注射液治疗糖尿病性多发性神经病变临床研究[J].辽宁中医杂志2009,36(3)：388-289.
14.张卫芳,欧燕华.丹红注射液治疗糖尿病周围神经病变25例疗效观察[J].吉林医学,2009,30(3)：247.
1. Dellon AL. Optimism in diabetic neuropathy. Ann Plast Surg,1988,20(2): 103-105.
2. Aszmann 0, Tassler PL, Dellon AL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53(6):517-522.
3. Dellon AL, Ebmer J, Swier P. Anatomic variation related to decompression of the common peroneal nerve at the fibular head. Ann Plast Surg,2002, 48(1):30-34.
4.张黎,于炎冰,林朋,等.正中神经显微减压术治疗糖尿病性上肢周围神经病.中华神经外科疾病研究杂志,2009,8(5)：453-455.
5.张黎,于炎冰,林朋,等.肘管尺神经显微减压术治疗糖尿病性上肢周围神经病.中国临床神经外科杂志,2007,12(8)：457-459.
6.姚勇,孟繁凯,王任直.应用周围神经松解术治疗糖尿病周围神经病.中国老年学杂志.2006,26：1054-1055.
7. Biddinger KR, Amend KA. The role of surgical decompression for diabetic neuropathy. Foot Ankle Clin Am,2004,9(2):239-254.
8. Dellon AL. Diabetic neuropathy:Review of a surgical approach to restore sensation, relieve pain, and prevent ulceration and amputation. Foot Ankle Int,2004,25(10):749-755.
9. Aszmann 0, Tassler PL, DellonAL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53 (6):517-522.
10. Dellon AL, Ebmer J, Swier P. Anatomic variationrelated to common peroneal nerve at the fibular head[J], Ann Plant Surg,2002,48:30-34.
11. Vinik AI. Diagnosis and management of diabetic neuropathy. Clin Geriatr Med,1999,15(2):293.
12. Aszmann OC, Kress KM, Dellon AL. Results of decompression of peripheral nerves in people with diabetes:a prospective, blinded study. Plast Reconstr Surg,2000,106(4):816-822.
13. Frykberg RG. Epidemiology of the diabetic foot:ulceration and amputation. Adv Wound Care,1999,12(3):139.
14. Matricali GA, Derook, Deremaeker G. Outcome and recurrence rate of diabetic foot ulcers treated by a total contact cast:short-term follow-up. Foot Ankle Int,2003,24(9)':680-684.
15. Ollendorf D, Kotsanos J, Wishner W. Potential economic benefits of lower-extremity amputation prevention strategies in diabetes. Diabetes Care,1998,21 (8):1240-1245.
1. Cefalu WT. Animal models of type 2 diabetes:clinical presentation and pathophysiological relevance to the human condition.[J].ILAR-J,2006,47: 186-198.
2. Lauriss G, Cornblathb DR, Johanssonc 0, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. [J]. Eur J Neurol,2005,13:747-758.
3. Mika Nakae, Hideki Kamiya, Keiko Naruse, et al. Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in rats. [J]. Diabetes,2006,55:1470-1477.
4. De Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. [J]. Exp Neurol,1982,77:634-643.
5. Upton AR, McComas AJ. Thedouble crush in nerve entrapment syndromes. [J]. Lancet,1973,2:359-362.
6.张黎,于炎冰,林朋,等.周围神经显微减压术治疗糖尿病性上肢周围神经病.[J].中华神经外科杂志,2009,25：315-317.
7.张黎,于炎冰,林朋,等.正中神经显微减压术治疗糖尿病性上肢周围神经病.[J].中华神经外科疾病研究杂志,2009,8：453-455.
[8.Ducic I, Felder JM, Iorio LM. The roleof peripheral nerve surgery in diabetic limb salvage. [J]. Plastic Reconstr Surg.2011,127:259S-269S.
9.Nickerson DS. Low recurrence rate of diabetic foot ulcer after nerve decompression. [J]. J Am Podiatr Med Assoc.2010,100:111-115.
10. Sumner CJ, Sheth S, Griffin JW, et al. The spectrum of neuropathy in diabetes and impaired glucosetolerance. [J]. Neurology,2003,60:108-111.
11.Shun CT, Chang YC, Wu HP, et al. Skin denervation in type2 diabetes: correlations with diabetic duration and functional impairments. [J]. Brain,2004,127:1593-1605.
1.曹延林,靳安民,张辉,等.脑源性神经生长因子基因转染对脊髓神经干细胞分化的影响[J].中华神经医学杂志,2011,10(3)：238-240.
2.李爽,马信龙,孙晓雷,等.改良冷喷注法纯化大鼠雪旺细胞的实验研究[J].中华神经医学杂志,2011,10(10)：1000-1004.
3.Han Is, Seo TB, Kim KH, et al. Cde2-mediated Schwann cell migration during peripheral nerve regeneration[J]. J Cell Sci,2007,120(2):246-255.
4. Tan W, Rouen S, Barkus K M, et al. Nerve growth factor blocks the glucose-induced down-regulation of caveolin-1 expression in Schwann cells via p75 neurotrophin receptor signaling[J]. J Biol Chem,2003,278 (25):23151-23162.
5.Shettar A, Muttagi G. Developmental regulation of insulin receptor gene in sciatic nerves and role of insulin on glycoprotein PO in the Schwann cells[J]. Peptides,2012,36(1):46-53.
6.赵步长.脑心同治——心脑血管疾病防治进展[M].北京：人民卫生出版社,2006：9.
7.牟春芬,韩丽丽.DH联合弥可保治疗糖尿病周围神经病变40例[J]. 光明中医,2010,25(2)：279-280.
8.吕树泉,张淑芳,苏秀海,等.糖尿病周围神经病变中医药治疗近况[J].现代中西医结合杂志,2013,22(4)：447-448.
9.赵云平.DH联合西药对糖尿病周围神经病变神经传导速度及神经生长相关因子的影响观察[J].世界中医药,2013,8(7)：750-752.
10.杨小艳,余昌胤,范瑞明,等.糖尿病大鼠缺血再灌注脑组织脑源性神经生长因子和碱性成纤维细胞生长因子的表达及意义[J].贵州医药,2008,32(2)：99-101.
11.劳杰,姜良福,顾玉东,等.脑源性神经营养因子在激活态许旺细胞中表达的初步实验研究[J].中华手外科杂志,2003,19(2)：109-111.
12.许珊丹,曾婧,陈冠民,等.神经生长因子在周围神经系统疾病中的临床应用[J]. 中国新药杂志,2004,13(7)：587-589.
13. Hidaka, H, M. Hagiwara, T. Chijiwa. Molecular pharmacology of protein kinases[J]. Neurosci. Res.1989,15(4):431-434.
14. A. Nitta, R. Murai, N. Suzuki, et al. Diabetic neuropathies in brain are induced by deficiency of BDNF [J]. Neurotoxicology and Teratology,2002, 24(5):695-701.
15.刘秀华,唐朝枢.细胞外信号引起细胞核反应的细胞信号转导系统[M].国外医学生理、病理科学与临床分册,1999,19(2)：88-91
16. Z Li,J Zhang, Z Liu, et al. Downregulation of Bim by brain-derived neurotrophic factor activation of TrKB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death [J]. Cell death and differentiation,2007,14:318-326.
17. David E, Dostal, George W, et al. Antiotensin II signaling pathways in cardiac fibroblasts:Conventional versus novel mechanisms in mediating cardiac growth and function[J]. Molecular and Cellular Biochemistry,1996,157:15-21.
18. Baines CP, Zhang J, Wang GW, et al. Mitochondrial PKCepsilon and MAPK form signaling molecules in the murine heart:enhanced mitochondrial PKCepsilon- MAPK interactions and differential MAPK activation in PKCepsilon- induced cardioprotection T[J]. Circ Res,2002,90(4):390-397.
1.王忠诚,主编.神经外科学.武汉：湖北科学技术出版社,2005：1092.
2. Lonze BE, Ginty DD.Function and regulation of CREB family transcription factors in the nervous system. Neuron,2002,35:605-623.
3.Ma W, Quirion R. Increased phosphorylation of cyclin AMP response element-binding protein(CREB) in the superficial dorsal horn neurons following partial sciatic nerve ligation. Pain,2001,93:295-301.
4.姚永兴,祝继洪,宋学军,等.慢性神经病理性疼痛大鼠背根神经节和脊髓背角pCREB表达的变化.中华麻醉学杂志,2006,26：173-176.
5.刘耀波,李昕,李尧华,等.外周神经损伤大鼠背根神经节中Ephrin B1及RYK受体表达的变化.基础医学与临床,2007,27(6)：605-609.
6. Devor M, Janig W, Michaelis M, et al. Modulation of activity in DRG neurons by sympathetic activation in nerve-injured rats. J Neurophysiol,1994,71(1):38.
7.胡道松,曹福元,徐清贵,等.外周神经损伤后对大鼠脊髓运动神经元及背根节感觉神经元的影响.同济医科大学学报,1999,28(6)：478-481.
8.谭爱娟,令狐清溪,王瑞.周围神经损伤后大鼠背根神经节细胞NMDA受体表达的可塑性改变.山西医科大学学报,2002,33(2)：97-98.
9. Radh akrishna M, Almazan G. Protein kinases mediate basicf ibroblast growth factors stimulation of proliferation and c-fos inductionin oligodend rocyte progenitors[J]. Brain ResMol Brain Res,1994,24:118.
10. Takemoto 0, Tomimoto H, Yanagihara T. Induction of c-fos and c-jun gene products and heat shock protein after brief and prolongedcerebral ischemia in gerbils[J]. Stoke,1995,26:1639.
11.Kovacs KJ.Invited review c-fos as a transcription factor:a stressfulreview from functional map. [J]. Neurochemistry International, 1998,33:287.
12.姚旭,丁新生,唐金荣,等.尼莫地平对急性损伤后大鼠背根神经节细胞c-fos、c-junmRNA表达的影响.临床神经病学杂志,2007,20(4)：295-298
13.Farlie PG, Dringen R, Rees SM, et al. Bcl-2 transgene expression can protect neurons against developmental and induced cell death. Proc Natl Acad Sci,1995,92:4001-4397.
14. Oltvai ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil death wishes. Cell,1994,79:189-192.
15.张文捷,周跃.坐骨神经损伤对背根节细胞凋亡及细胞凋亡相关蛋白表达的影响.中华手外科杂志,2001,17(3)：159-162.
16. Wen X, Tresco PA. Effect of Filament Diameterand Extracellular Matrix Molecule Precoating on Neurite Outgrowth and Schwann Cell Behavior on Multifilament Entubulation Bridging Device in Vitro [J]. J Biomed Mater Res A(S1549-3296),2006,76 (3):626-637.
17. Liang GS, Demiguel M, GOMEZH ERN NDEZJM, et al. Severe Neuropathy with Leaky Connex in32Hemichannels[J].Ann Neurol (S0364-5134), 2005,57 (5):749-754.
18. Azanchi R, Bernal G, Gupta R, etal. Combined demyelination plus Schwann cell transplantation therapy increasesspread of cells and axonal regeneration following contusion injury. J Neurotrauma,2004,21 (6):775-788.
19. TuszynskiMH, Grill R, Jones LL, et al. Spon taneous andaugmented growth of axons in the primate spinal cord:effectsof local injury and nerve growth factor-secreting cell grafts. JComp Neu rol,2002,449(1):88-101.
20. Hanls, seo TB, Kim HK, et al. Cde2-mediated Schwann cell migration during peripheral nerve regeneration[J]. J Cell Sci,2007,120:246-255.
21. Tan W, Rouen S, Barkus KM, et al. Nerve growth factor blocks the glucose-induced down-regulation of caveolin-1 experssion in Schwann cells via p75 neurotrophin receptor signal ing[J]. J Biol Chem,2003,278: 23151-23162.
22. Dobmwsky RT, Rouen S, Yu C. Altered neurotrophism in diabeticneuropathy: Spelunking the caves of peripheral nerve. Pharmacol ExpTher,2005,313: 485-491.
23.Zhu H, Yu WJ, Le Y, et al. High glucose levels increase the expression of neurotrophic factors associated with p-p42/p44 MAPK in Schwann cells in vitro. Mol Med Rep.2012 Jul;6:179-84.
24.朱敏,沈爱国,丁斐,等.β-1,4半乳糖基转移酶-Ⅰ在大鼠坐骨神经损伤后的表达变化[J].中国组织化学与细胞化学杂志,2003,12(3)：317-322.
25.朱敏,沈爱国,丁斐,等.Galβ-1,4-GlcNAc在钳夹伤后大鼠坐骨神经中的表达变化[J].中国临床解剖学杂志,2006,24(6)：658-661.
26. Ohta M, Ohi T, Nishmura M, et al. Distribution of and age-related changes in ciliary neurotrophic factor protein in rat tissues. Biochem Mol Biol Int,1996,40(4):671-678.
27.Daves A M. Role of neurotrophic factor in development. Trends Gene,1988, 4(5):139-143.
28. Oliveira RB, Ochoa MT, Sieling PA,et al. Expression of Toll-like receptor 2 on human Schwann cells:a mechanism of nerve damage in leprosy. Infect Immun,2003,71:127-1433.
29. Kawai T, Akirre S. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci,2008,1143:1-20.
30. Goethals S, Ydens E, Timmerman V, et al. Toll-like receptor expression in the peripheral nerve. Glia,2010,58:1701-1709
31.Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration:gaining perspective on inflammatory events after peripheral nerve injury.J Neuroinflammation,2011,8:110.
32.Lee H,Jo EK, Choi SY,et al.Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3:implication in Wallerian degeneration. Biochem Biophys Res Commun,2006,350(3):742-743
33.王国英,胡耀民,钟世镇.巨噬细胞在周围神经损伤和再生中的行为及其作用.神经解剖学杂志,1994,10：83-88.
34. Perry VH, Brown MC. Role of macrophages in peripheral nervedegeneration and repair. Bioessays,1992,14:401-406
35.黄涛,秦建强,刘大庸,等.外周神经损伤后许旺氏细胞激活巨噬细胞的实验研 究.中华显微外科杂志,2002,25(3)：192-193
36. Parrinello S, Napoli I, Ribeiro S, Digby 1 PW, Fedorova M, Parkinson DB, Doddrell RD, Nakayama M, Adams RH,Lloyd AC. EphB signaling directs peripheral nerve regenerationthrough Sox2-dependent Schwann cell sorting. Cell,2010,143(1):145-155.
2.王汉兵,王焱林,欧伟明,等.糖尿病周围神经病变大鼠疼痛模型的建立[J].中国疼痛医学杂志,2007,13(1)：45—46.
3. Ohman CL, Coppey LJ, Gellett JS, et al. Progression of vascularand neuraldysfunctionin sciatic nervesof Zucker diabeticfattyand Zucker rats[J]. AmJPhysiol Endocrinol Metab,2005,289(1):E113-122.
4. Katarzyna Kotulska, Wieslaw Marrcol, Magdalena Larysz-Brysz, et al. Impaired regeneration of Bcl-2 lacking peripheral nerves. Neurological Research,2005,27(12):843-849.
5. Srinivasuwa SM, Ahmad M, Ternandes-Alnermri. Molicular ordering of the Fas-apoptotic pathway:the Fas/APO-1 protease Mch5 is a Crma-inhibitable protease that activates multiple Ced-3/ICE-like cystein protease[J]. Pro. Natl. Acad. Sci. USA,1996,9 (2) 3:14486-14491.
6.Zochodne DW, ChengC. Neurotrophins andothergrowsfactors intheregenerativemilieu ofproximalnerve stumptips Anat.2002; 196:279-228.
7.Xu G, Sima AAF. Altered immediate early gene expression is injured in diabetic nerve:implications in re generation[J].J Neuro pathol Exp Neuro 1,2001,60(10):972-983.
8.Xu G,Murakawa Y, Pierson CR, et al. Altered (i-tubulin and neuro fila-ment expression and impaired axonal gro wth in diabetic nerve regenera-tion[J]. J Neuro path Exp Neuro 1,2002,61(2):164-175.
9. Gordois A, Oglesby A, Scuffham P, et al. The health care costs of diabetic peripheral neuropathy in the U.S. Diabetes Care,2003,26(6):1790-1795. 10. Dellon AL. Optimism in diabetic neuropathy. Ann Plast Surg,1988,20(2): 103-105.
11. Aszmann 0, Tassler PL, Dellon AL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53(6):517-522.
12.任荣.丹红注射液治疗糖尿病周围神经病变的疗效观察[J].中西医结合心脑血管病杂志,2008,6(12)：1489-1499.
13.陈济洲,赵健雄,乔成栋.丹红注射液治疗糖尿病性多发性神经病变临床研究[J].辽宁中医杂志2009,36(3)：388-289.
14.张卫芳,欧燕华.丹红注射液治疗糖尿病周围神经病变25例疗效观察[J].吉林医学,2009,30(3)：247.
1. Dellon AL. Optimism in diabetic neuropathy. Ann Plast Surg,1988,20(2): 103-105.
2. Aszmann 0, Tassler PL, Dellon AL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53(6):517-522.
3. Dellon AL, Ebmer J, Swier P. Anatomic variation related to decompression of the common peroneal nerve at the fibular head. Ann Plast Surg,2002, 48(1):30-34.
4.张黎,于炎冰,林朋,等.正中神经显微减压术治疗糖尿病性上肢周围神经病.中华神经外科疾病研究杂志,2009,8(5)：453-455.
5.张黎,于炎冰,林朋,等.肘管尺神经显微减压术治疗糖尿病性上肢周围神经病.中国临床神经外科杂志,2007,12(8)：457-459.
6.姚勇,孟繁凯,王任直.应用周围神经松解术治疗糖尿病周围神经病.中国老年学杂志.2006,26：1054-1055.
7. Biddinger KR, Amend KA. The role of surgical decompression for diabetic neuropathy. Foot Ankle Clin Am,2004,9(2):239-254.
8. Dellon AL. Diabetic neuropathy:Review of a surgical approach to restore sensation, relieve pain, and prevent ulceration and amputation. Foot Ankle Int,2004,25(10):749-755.
9. Aszmann 0, Tassler PL, DellonAL. Changing the natural history of diabetic neuropathy:incidence of ulcer/amputation in the contralateral limb of patients with a unilateral nerve decompression procedure. Ann Plast Surg, 2004,53 (6):517-522.
10. Dellon AL, Ebmer J, Swier P. Anatomic variationrelated to common peroneal nerve at the fibular head[J], Ann Plant Surg,2002,48:30-34.
11. Vinik AI. Diagnosis and management of diabetic neuropathy. Clin Geriatr Med,1999,15(2):293.
12. Aszmann OC, Kress KM, Dellon AL. Results of decompression of peripheral nerves in people with diabetes:a prospective, blinded study. Plast Reconstr Surg,2000,106(4):816-822.
13. Frykberg RG. Epidemiology of the diabetic foot:ulceration and amputation. Adv Wound Care,1999,12(3):139.
14. Matricali GA, Derook, Deremaeker G. Outcome and recurrence rate of diabetic foot ulcers treated by a total contact cast:short-term follow-up. Foot Ankle Int,2003,24(9)':680-684.
15. Ollendorf D, Kotsanos J, Wishner W. Potential economic benefits of lower-extremity amputation prevention strategies in diabetes. Diabetes Care,1998,21 (8):1240-1245.
1. Cefalu WT. Animal models of type 2 diabetes:clinical presentation and pathophysiological relevance to the human condition.[J].ILAR-J,2006,47: 186-198.
2. Lauriss G, Cornblathb DR, Johanssonc 0, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. [J]. Eur J Neurol,2005,13:747-758.
3. Mika Nakae, Hideki Kamiya, Keiko Naruse, et al. Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in rats. [J]. Diabetes,2006,55:1470-1477.
4. De Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. [J]. Exp Neurol,1982,77:634-643.
5. Upton AR, McComas AJ. Thedouble crush in nerve entrapment syndromes. [J]. Lancet,1973,2:359-362.
6.张黎,于炎冰,林朋,等.周围神经显微减压术治疗糖尿病性上肢周围神经病.[J].中华神经外科杂志,2009,25：315-317.
7.张黎,于炎冰,林朋,等.正中神经显微减压术治疗糖尿病性上肢周围神经病.[J].中华神经外科疾病研究杂志,2009,8：453-455.
[8.Ducic I, Felder JM, Iorio LM. The roleof peripheral nerve surgery in diabetic limb salvage. [J]. Plastic Reconstr Surg.2011,127:259S-269S.
9.Nickerson DS. Low recurrence rate of diabetic foot ulcer after nerve decompression. [J]. J Am Podiatr Med Assoc.2010,100:111-115.
10. Sumner CJ, Sheth S, Griffin JW, et al. The spectrum of neuropathy in diabetes and impaired glucosetolerance. [J]. Neurology,2003,60:108-111.
11.Shun CT, Chang YC, Wu HP, et al. Skin denervation in type2 diabetes: correlations with diabetic duration and functional impairments. [J]. Brain,2004,127:1593-1605.
1.曹延林,靳安民,张辉,等.脑源性神经生长因子基因转染对脊髓神经干细胞分化的影响[J].中华神经医学杂志,2011,10(3)：238-240.
2.李爽,马信龙,孙晓雷,等.改良冷喷注法纯化大鼠雪旺细胞的实验研究[J].中华神经医学杂志,2011,10(10)：1000-1004.
3.Han Is, Seo TB, Kim KH, et al. Cde2-mediated Schwann cell migration during peripheral nerve regeneration[J]. J Cell Sci,2007,120(2):246-255.
4. Tan W, Rouen S, Barkus K M, et al. Nerve growth factor blocks the glucose-induced down-regulation of caveolin-1 expression in Schwann cells via p75 neurotrophin receptor signaling[J]. J Biol Chem,2003,278 (25):23151-23162.
5.Shettar A, Muttagi G. Developmental regulation of insulin receptor gene in sciatic nerves and role of insulin on glycoprotein PO in the Schwann cells[J]. Peptides,2012,36(1):46-53.
6.赵步长.脑心同治——心脑血管疾病防治进展[M].北京：人民卫生出版社,2006：9.
7.牟春芬,韩丽丽.DH联合弥可保治疗糖尿病周围神经病变40例[J]. 光明中医,2010,25(2)：279-280.
8.吕树泉,张淑芳,苏秀海,等.糖尿病周围神经病变中医药治疗近况[J].现代中西医结合杂志,2013,22(4)：447-448.
9.赵云平.DH联合西药对糖尿病周围神经病变神经传导速度及神经生长相关因子的影响观察[J].世界中医药,2013,8(7)：750-752.
10.杨小艳,余昌胤,范瑞明,等.糖尿病大鼠缺血再灌注脑组织脑源性神经生长因子和碱性成纤维细胞生长因子的表达及意义[J].贵州医药,2008,32(2)：99-101.
11.劳杰,姜良福,顾玉东,等.脑源性神经营养因子在激活态许旺细胞中表达的初步实验研究[J].中华手外科杂志,2003,19(2)：109-111.
12.许珊丹,曾婧,陈冠民,等.神经生长因子在周围神经系统疾病中的临床应用[J]. 中国新药杂志,2004,13(7)：587-589.
13. Hidaka, H, M. Hagiwara, T. Chijiwa. Molecular pharmacology of protein kinases[J]. Neurosci. Res.1989,15(4):431-434.
14. A. Nitta, R. Murai, N. Suzuki, et al. Diabetic neuropathies in brain are induced by deficiency of BDNF [J]. Neurotoxicology and Teratology,2002, 24(5):695-701.
15.刘秀华,唐朝枢.细胞外信号引起细胞核反应的细胞信号转导系统[M].国外医学生理、病理科学与临床分册,1999,19(2)：88-91
16. Z Li,J Zhang, Z Liu, et al. Downregulation of Bim by brain-derived neurotrophic factor activation of TrKB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death [J]. Cell death and differentiation,2007,14:318-326.
17. David E, Dostal, George W, et al. Antiotensin II signaling pathways in cardiac fibroblasts:Conventional versus novel mechanisms in mediating cardiac growth and function[J]. Molecular and Cellular Biochemistry,1996,157:15-21.
18. Baines CP, Zhang J, Wang GW, et al. Mitochondrial PKCepsilon and MAPK form signaling molecules in the murine heart:enhanced mitochondrial PKCepsilon- MAPK interactions and differential MAPK activation in PKCepsilon- induced cardioprotection T[J]. Circ Res,2002,90(4):390-397.
1.王忠诚,主编.神经外科学.武汉：湖北科学技术出版社,2005：1092.
2. Lonze BE, Ginty DD.Function and regulation of CREB family transcription factors in the nervous system. Neuron,2002,35:605-623.
3.Ma W, Quirion R. Increased phosphorylation of cyclin AMP response element-binding protein(CREB) in the superficial dorsal horn neurons following partial sciatic nerve ligation. Pain,2001,93:295-301.
4.姚永兴,祝继洪,宋学军,等.慢性神经病理性疼痛大鼠背根神经节和脊髓背角pCREB表达的变化.中华麻醉学杂志,2006,26：173-176.
5.刘耀波,李昕,李尧华,等.外周神经损伤大鼠背根神经节中Ephrin B1及RYK受体表达的变化.基础医学与临床,2007,27(6)：605-609.
6. Devor M, Janig W, Michaelis M, et al. Modulation of activity in DRG neurons by sympathetic activation in nerve-injured rats. J Neurophysiol,1994,71(1):38.
7.胡道松,曹福元,徐清贵,等.外周神经损伤后对大鼠脊髓运动神经元及背根节感觉神经元的影响.同济医科大学学报,1999,28(6)：478-481.
8.谭爱娟,令狐清溪,王瑞.周围神经损伤后大鼠背根神经节细胞NMDA受体表达的可塑性改变.山西医科大学学报,2002,33(2)：97-98.
9. Radh akrishna M, Almazan G. Protein kinases mediate basicf ibroblast growth factors stimulation of proliferation and c-fos inductionin oligodend rocyte progenitors[J]. Brain ResMol Brain Res,1994,24:118.
10. Takemoto 0, Tomimoto H, Yanagihara T. Induction of c-fos and c-jun gene products and heat shock protein after brief and prolongedcerebral ischemia in gerbils[J]. Stoke,1995,26:1639.
11.Kovacs KJ.Invited review c-fos as a transcription factor:a stressfulreview from functional map. [J]. Neurochemistry International, 1998,33:287.
12.姚旭,丁新生,唐金荣,等.尼莫地平对急性损伤后大鼠背根神经节细胞c-fos、c-junmRNA表达的影响.临床神经病学杂志,2007,20(4)：295-298
13.Farlie PG, Dringen R, Rees SM, et al. Bcl-2 transgene expression can protect neurons against developmental and induced cell death. Proc Natl Acad Sci,1995,92:4001-4397.
14. Oltvai ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil death wishes. Cell,1994,79:189-192.
15.张文捷,周跃.坐骨神经损伤对背根节细胞凋亡及细胞凋亡相关蛋白表达的影响.中华手外科杂志,2001,17(3)：159-162.
16. Wen X, Tresco PA. Effect of Filament Diameterand Extracellular Matrix Molecule Precoating on Neurite Outgrowth and Schwann Cell Behavior on Multifilament Entubulation Bridging Device in Vitro [J]. J Biomed Mater Res A(S1549-3296),2006,76 (3):626-637.
17. Liang GS, Demiguel M, GOMEZH ERN NDEZJM, et al. Severe Neuropathy with Leaky Connex in32Hemichannels[J].Ann Neurol (S0364-5134), 2005,57 (5):749-754.
18. Azanchi R, Bernal G, Gupta R, etal. Combined demyelination plus Schwann cell transplantation therapy increasesspread of cells and axonal regeneration following contusion injury. J Neurotrauma,2004,21 (6):775-788.
19. TuszynskiMH, Grill R, Jones LL, et al. Spon taneous andaugmented growth of axons in the primate spinal cord:effectsof local injury and nerve growth factor-secreting cell grafts. JComp Neu rol,2002,449(1):88-101.
20. Hanls, seo TB, Kim HK, et al. Cde2-mediated Schwann cell migration during peripheral nerve regeneration[J]. J Cell Sci,2007,120:246-255.
21. Tan W, Rouen S, Barkus KM, et al. Nerve growth factor blocks the glucose-induced down-regulation of caveolin-1 experssion in Schwann cells via p75 neurotrophin receptor signal ing[J]. J Biol Chem,2003,278: 23151-23162.
22. Dobmwsky RT, Rouen S, Yu C. Altered neurotrophism in diabeticneuropathy: Spelunking the caves of peripheral nerve. Pharmacol ExpTher,2005,313: 485-491.
23.Zhu H, Yu WJ, Le Y, et al. High glucose levels increase the expression of neurotrophic factors associated with p-p42/p44 MAPK in Schwann cells in vitro. Mol Med Rep.2012 Jul;6:179-84.
24.朱敏,沈爱国,丁斐,等.β-1,4半乳糖基转移酶-Ⅰ在大鼠坐骨神经损伤后的表达变化[J].中国组织化学与细胞化学杂志,2003,12(3)：317-322.
25.朱敏,沈爱国,丁斐,等.Galβ-1,4-GlcNAc在钳夹伤后大鼠坐骨神经中的表达变化[J].中国临床解剖学杂志,2006,24(6)：658-661.
26. Ohta M, Ohi T, Nishmura M, et al. Distribution of and age-related changes in ciliary neurotrophic factor protein in rat tissues. Biochem Mol Biol Int,1996,40(4):671-678.
27.Daves A M. Role of neurotrophic factor in development. Trends Gene,1988, 4(5):139-143.
28. Oliveira RB, Ochoa MT, Sieling PA,et al. Expression of Toll-like receptor 2 on human Schwann cells:a mechanism of nerve damage in leprosy. Infect Immun,2003,71:127-1433.
29. Kawai T, Akirre S. Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci,2008,1143:1-20.
30. Goethals S, Ydens E, Timmerman V, et al. Toll-like receptor expression in the peripheral nerve. Glia,2010,58:1701-1709
31.Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration:gaining perspective on inflammatory events after peripheral nerve injury.J Neuroinflammation,2011,8:110.
32.Lee H,Jo EK, Choi SY,et al.Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3:implication in Wallerian degeneration. Biochem Biophys Res Commun,2006,350(3):742-743
33.王国英,胡耀民,钟世镇.巨噬细胞在周围神经损伤和再生中的行为及其作用.神经解剖学杂志,1994,10：83-88.
34. Perry VH, Brown MC. Role of macrophages in peripheral nervedegeneration and repair. Bioessays,1992,14:401-406
35.黄涛,秦建强,刘大庸,等.外周神经损伤后许旺氏细胞激活巨噬细胞的实验研 究.中华显微外科杂志,2002,25(3)：192-193
36. Parrinello S, Napoli I, Ribeiro S, Digby 1 PW, Fedorova M, Parkinson DB, Doddrell RD, Nakayama M, Adams RH,Lloyd AC. EphB signaling directs peripheral nerve regenerationthrough Sox2-dependent Schwann cell sorting. Cell,2010,143(1):145-155.