Qian-Zheng-San promotes regeneration after sciatic nerve crush injury in rats
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摘要
Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San(1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that QianZheng-San has a positive effect on peripheral nerve regeneration.
Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San(1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that QianZheng-San has a positive effect on peripheral nerve regeneration.
Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San(1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that QianZheng-San has a positive effect on peripheral nerve regeneration.
引文
Adam KR,Schmidt H,Stampfli R,Weiss C(1966)The effect of scorpion venom on single myelinated nerve fibres of the frog.Br J Pharmacol Chemother 26:666-677.
Allen SJ,Watson JJ,Shoemark DK,Barua NU,Patel NK(2013)GDNF,NGF and BDNF as therapeutic options for neurodegeneration.Pharmacol Ther 138:155-175.
Catapano J,Zhang J,Scholl D,Chiang C,Gordon T,Borschel GH(2017)N-acetylcysteine prevents retrograde motor neuron death after neonatal peripheral nerve injury.Plast Reconstr Surg 139:1105-1115.
Chen J,Chu YF,Chen JM,Li BC(2010)Synergistic effects of NGF,CNTF and GDNF on functional recovery following sciatic nerve injury in rats.Adv Med Sci 55:32-42.
Demir R,Yayla M,Akpinar E,Cakir M,Calikoglu C,Ozel L,Ozdemir G,Mercantepe T(2014)Protective effects of alpha-lipoic acid on experimental sciatic nerve crush injury in rats:assessed with functional,molecular and electromicroscopic analyses.Int J Neurosci124:935-943.
Gong XG,Sun HM,Zhang Y,Zhang SJ,Gao YS,Feng J,Hu JH,Gai C,Guo ZY,Xu H,Ma L(2014)Da-Bu-Yin-Wan and Qian-Zheng-San to neuroprotect the mouse model of Parkinson’s disease.Evid Based Complement Alternat Med 2014:729195.
Gordon T(2010)The physiology of neural injury and regeneration:The role of neurotrophic factors.J Commun Disord 43:265-273.
He X,Gao YS,Sun HM,Wu HX,Xu H,Wang ZY(2010)Effect of Dabuyin Pill and Qianzheng Powder on activity of mitochondrial enzyme complexes in mice with Parkinson’s disease.Jiangsu Zhongyi 42:72-73.
He XZ,Wang W,Hu TM,Ma JJ,Yu CY,Gao YF,Cheng XL,Wang P(2016)Peripheral nerve repair:theory and technology application.Zhongguo Zuzhi Gongcheng Yanjiu 20:1044-1050.
Hu X,Huang J,Ye Z,Xia L,Li M,Lv B,Shen X,Luo Z(2009)A novel scaffold with longitudinally oriented microchannels promotes peripheral nerve regeneration.Tissue Eng 15:3297-3308.
Huang EJ,Reichardt LF(2001)Neurotrophins:roles in neuronal development and function.Annu Rev Neurosci 24:677-736.
Huang J,Zhang Y,Lu L,Hu X,Luo Z(2013)Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.Eur J Neurosci 38:3691-3701.
Jiang B,Zhang P,Zhang D,Fu Z,Yin X,Zhang H(2006)Study on small gap sleeve bridging peripheral nerve injury.Artif Cells Blood Substit Immobil Biotechnol 34:55-74.
Jiang BG,Yin XF,Zhang DY,Fu ZG,Zhang HB(2007)Maximum number of collaterals developed by one axon during peripheral nerve regeneration and the influence of that number on reinnervation effects.Eur Neurol 58:12-20.
Kou Y,Wang Z,Wu Z,Zhang P,Zhang Y,Yin X,Wong X,Qiu G,Jiang B(2013)Epimedium extract promotes peripheral nerve regeneration in rats.Evid Based Complement Alternat Med 954798.
Lewin GR,Rueff A,Mendell LM(1994)Peripheral and central mechanisms of NGF-induced hyperalgesia.Eur J Neurosci 6:1903-1912.
Li Q,Li T,Cao XC,Luo DQ,Lian KJ(2016)Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion.Neural Regen Res 11:835-841.
Mozhaeva GN,Naumov AP(1980)Kinetics of the reaction between scorpion toxin and the sodium channels of nodes of Ranvier.Neirofiziologiia 12:619-626.
Ni Q,Chen W,Tong L,Cao J,Ji C(2016)Preparation of novel biodegradable ropivacaine microspheres and evaluation of their efficacy in sciatic nerve block in mice.Drug Des Devel Ther 10:2499-2506.
R?ducan A,Miric?S,Duicu O,R?ducan S,Muntean D,Fira-Ml?dinescu O,Lighezan R(2013)Morphological and functional aspects of sciatic nerve regeneration after crush injury.Rom J Morphol Embryol 54:735-739.
Renno WM,AL-maghrebi M,Rao MS,Khraishah H(2015)(-)-Epigallocatechin-3-gallate modulates spinal cord neuronal degeneration by enhancing growth-associated protein 43,B-cell lymphoma 2,and decreasing B-cell lymphoma 2-associated x protein expression after sciatic nerve crush injury.J Neurotrauma 32:170-184.
Roam JL,Yan Y,Nguyen PK,Kinstlinger IS,Leuchter MK,Hunter DA,Wood MD,Elbert DL(2015)A modular,plasmin-sensitive,clickable poly(ethylene glycol)-heparin-laminin microsphere system for establishing growth factor gradients in nerve guidance conduits.Biomaterials 72:112-124.
Sacchetti M,Lambiase A(2017)Neurotrophic factors and corneal nerve regeneration.Neural Regen Res 12:1220-1224.
Shakhbazau A,Mohanty C,Shcharbin D,Bryszewska M,Caminade AM,Majoral JP,Alant J,Midha R(2013)Doxycycline-regulated GDNF expression promotes axonal regeneration and functional recovery in transected peripheral nerve.J Control Release 172:841-851.
Shan BE,Zhang JY,Li QX(2001)Human T cell and monocyte modulating activity of Rhizoma typhonii in vitro.Zhongguo Zhong Xi Yi Jie He Za Zhi 21:768-772.
Si HB,Zeng Y,Lu YR,Cheng JQ,Shen B(2017)Control-released basic fibroblast growth factor-loaded poly-lactic-co-glycolic acid microspheres promote sciatic nerve regeneration in rats.Exp Ther Med13:429-436.
Sun W,Sun C,Lin H,Zhao H,Wang J,Ma H,Chen B,Xiao Z,Dai J(2009)The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model.Biomaterials 30:4649-4656.
Tria MA,Fusco M,Vantini G,Mariot R(1994)Pharmacokinetics of nerve growth factor(NGF)following different routes of administration to adult rats.Exp Neurol 127:178-183.
Tsai CC,Lu MC,Chen YS,Wu CH,Lin CC(2003)Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration.Am J Chin Med 31:665-673.
Wang CZ,Chen YJ,Wang YH,Yeh ML,Huang MH,Ho ML,Liang JI,Chen CH(2014)Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.PLoS One 9:e103348.
Wang D,Li ZM,Zhao MJ,Xue RH,Xu H,Zhong LM(2018a)Neuroelectrophysiological characteristics of peripheral neuropathy in primary Sj?gren’s syndrome:study protocol for a prospective case series and pre-preliminary results.Asia Pac J Clin Trials Nerv Syst Dis 2018;3:68-73
Wang Z,Zhang P,Kou Y,Yin X,Han N,Jiang B(2013a)Hedysari extract improves regeneration after peripheral nerve injury by enhancing the amplification effect.PLos One 8:e67921.
Wang Z,Yang X,Zhang W,Zhang P,Jiang B(2018b)Tanshinone IIAattenuates nerve structural and functional damage induced by nerve crush injury in rats.PLoS One 13:e0202532.
Wang ZY,Zhang PX,Han N,Kou YH,Yin XF,Jiang BG(2013b)Effect of modified formula radix hedysari on the amplification effect during peripheral nerve regeneration.Evid Based Complement Alternat Med 2013:647982.
West CA,Davies KA,Hart AM,Wiberg M,Williams SR,Terenghi G(2007)Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury.Exp Neurol 203:22-33.
West CA,Ljungberg C,Wiberg M,Hart A(2013)Sensory neuron death after upper limb nerve injury and protective effect of repair:clinical evaluation using volumetric magnetic resonance imaging of dorsal root Ganglia.Neurosurgery 73:632-640.
Wojcikowski K,Gobe G(2014)Animal studies on medicinal herbs:predictability,dose conversion and potential value.Phytother Res28:22-27.
Wood MD,Gordon T,Kim H,Szynkaruk M,Phua P,Lafontaine C,Kemp SW,Shoichet MS,Borschel GH(2013)Fibrin gels containing GDNF microspheres increase axonal regeneration after delayed peripheral nerve repair.Regen Med 8:27-37.
Wood MD,Hunter D,Mackinnon SE,Sakiyama-Elbert SE(2010)Heparin-binding-affinity-based delivery systems releasing nerve growth factor enhance sciatic nerve regeneration.J Biomater Sci Polym Ed21:771-787.
Yang CC,Wang J,Chen SC,Jan YM,Hsieh YL(2015)Enhanced functional recovery from sciatic nerve crush injury through a combined treatment of cold-water swimming and mesenchymal stem cell transplantation.Neurol Res 37:816-826.
Yang JS(2010)Treatment for cold type facial paralysis by modified Qian Zheng San together with Ginger moxibustion.Zhongyi Zazhi7:71-74.
Yu H,Peng J,Guo Q,Zhang L,Li Z,Zhao B,Sui X,Wang Y,Xu W,Lu S(2009)Improvement of peripheral nerve regeneration in acellular nerve grafts with local release of nerve growth factor.Microsurgery29:330-336.
Zeng W,Rong M,Hu X,Xiao W,Qi F,Huang J,Luo Z(2014)Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor.PLoS One 9:e101300.
Zhang P,Zhang C,Kou Y,Yin X,Zhang H,Jiang B(2009)The histological analysis of biological conduit sleeve bridging rhesus monkey median nerve injury with small gap.Artif Cells Blood Substit Immobil Biotechnol 37:101-104.
Zhang P,Kou Y,Yin X,Wang Y,Zhang H,Jiang B(2011)The experimental research of nerve fibers compensation amplification innervation of ulnar nerve and musculocutaneous nerve in rhesus monkeys.Artif Cells Blood Substit Immobil Biotechnol 39:39-43.
Zhang P,Wang Z,Kou Y,Han N,Xu C,Yin X,Wang Y,Feng X(2014)Role of lumbricus extract in the nerve amplification effect during peripheral nerve regeneration.Am J Transl Res 6:876-885.
Zhang W,Zhou G,Gao Y,Zhou Y,Liu J,Zhang L,Long A,Zhang L,Tang P(2017)A sequential delivery system employing the synergism of EPO and NGF promotes sciatic nerve repair.Colloids Surf BBiointerfaces 159:327-336.
Zhang Y,Sun HM,He X,Wang YY,Gao YS,Wu HX,Xu H,Gong XG,Guo ZY(2013)Da-Bu-Yin-Wan and Qian-Zheng-San,two traditional Chinese herbal formulas,up-regulate the expression of mitochondrial subunit NADH dehydrogenase 1 synergistically in the mice model of Parkinson’s disease.J Ethnopharmacol 146:363-371.
Zhuang H,Bu S,Hua L,Darabi MA,Cao X,Xing M(2016)Gelatin-methacrylamide gel loaded with microspheres to deliver GDNFin bilayer collagen conduit promoting sciatic nerve growth.Int JNanomedicine 11:1383-1394.
Allen SJ,Watson JJ,Shoemark DK,Barua NU,Patel NK(2013)GDNF,NGF and BDNF as therapeutic options for neurodegeneration.Pharmacol Ther 138:155-175.
Catapano J,Zhang J,Scholl D,Chiang C,Gordon T,Borschel GH(2017)N-acetylcysteine prevents retrograde motor neuron death after neonatal peripheral nerve injury.Plast Reconstr Surg 139:1105-1115.
Chen J,Chu YF,Chen JM,Li BC(2010)Synergistic effects of NGF,CNTF and GDNF on functional recovery following sciatic nerve injury in rats.Adv Med Sci 55:32-42.
Demir R,Yayla M,Akpinar E,Cakir M,Calikoglu C,Ozel L,Ozdemir G,Mercantepe T(2014)Protective effects of alpha-lipoic acid on experimental sciatic nerve crush injury in rats:assessed with functional,molecular and electromicroscopic analyses.Int J Neurosci124:935-943.
Gong XG,Sun HM,Zhang Y,Zhang SJ,Gao YS,Feng J,Hu JH,Gai C,Guo ZY,Xu H,Ma L(2014)Da-Bu-Yin-Wan and Qian-Zheng-San to neuroprotect the mouse model of Parkinson’s disease.Evid Based Complement Alternat Med 2014:729195.
Gordon T(2010)The physiology of neural injury and regeneration:The role of neurotrophic factors.J Commun Disord 43:265-273.
He X,Gao YS,Sun HM,Wu HX,Xu H,Wang ZY(2010)Effect of Dabuyin Pill and Qianzheng Powder on activity of mitochondrial enzyme complexes in mice with Parkinson’s disease.Jiangsu Zhongyi 42:72-73.
He XZ,Wang W,Hu TM,Ma JJ,Yu CY,Gao YF,Cheng XL,Wang P(2016)Peripheral nerve repair:theory and technology application.Zhongguo Zuzhi Gongcheng Yanjiu 20:1044-1050.
Hu X,Huang J,Ye Z,Xia L,Li M,Lv B,Shen X,Luo Z(2009)A novel scaffold with longitudinally oriented microchannels promotes peripheral nerve regeneration.Tissue Eng 15:3297-3308.
Huang EJ,Reichardt LF(2001)Neurotrophins:roles in neuronal development and function.Annu Rev Neurosci 24:677-736.
Huang J,Zhang Y,Lu L,Hu X,Luo Z(2013)Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.Eur J Neurosci 38:3691-3701.
Jiang B,Zhang P,Zhang D,Fu Z,Yin X,Zhang H(2006)Study on small gap sleeve bridging peripheral nerve injury.Artif Cells Blood Substit Immobil Biotechnol 34:55-74.
Jiang BG,Yin XF,Zhang DY,Fu ZG,Zhang HB(2007)Maximum number of collaterals developed by one axon during peripheral nerve regeneration and the influence of that number on reinnervation effects.Eur Neurol 58:12-20.
Kou Y,Wang Z,Wu Z,Zhang P,Zhang Y,Yin X,Wong X,Qiu G,Jiang B(2013)Epimedium extract promotes peripheral nerve regeneration in rats.Evid Based Complement Alternat Med 954798.
Lewin GR,Rueff A,Mendell LM(1994)Peripheral and central mechanisms of NGF-induced hyperalgesia.Eur J Neurosci 6:1903-1912.
Li Q,Li T,Cao XC,Luo DQ,Lian KJ(2016)Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion.Neural Regen Res 11:835-841.
Mozhaeva GN,Naumov AP(1980)Kinetics of the reaction between scorpion toxin and the sodium channels of nodes of Ranvier.Neirofiziologiia 12:619-626.
Ni Q,Chen W,Tong L,Cao J,Ji C(2016)Preparation of novel biodegradable ropivacaine microspheres and evaluation of their efficacy in sciatic nerve block in mice.Drug Des Devel Ther 10:2499-2506.
R?ducan A,Miric?S,Duicu O,R?ducan S,Muntean D,Fira-Ml?dinescu O,Lighezan R(2013)Morphological and functional aspects of sciatic nerve regeneration after crush injury.Rom J Morphol Embryol 54:735-739.
Renno WM,AL-maghrebi M,Rao MS,Khraishah H(2015)(-)-Epigallocatechin-3-gallate modulates spinal cord neuronal degeneration by enhancing growth-associated protein 43,B-cell lymphoma 2,and decreasing B-cell lymphoma 2-associated x protein expression after sciatic nerve crush injury.J Neurotrauma 32:170-184.
Roam JL,Yan Y,Nguyen PK,Kinstlinger IS,Leuchter MK,Hunter DA,Wood MD,Elbert DL(2015)A modular,plasmin-sensitive,clickable poly(ethylene glycol)-heparin-laminin microsphere system for establishing growth factor gradients in nerve guidance conduits.Biomaterials 72:112-124.
Sacchetti M,Lambiase A(2017)Neurotrophic factors and corneal nerve regeneration.Neural Regen Res 12:1220-1224.
Shakhbazau A,Mohanty C,Shcharbin D,Bryszewska M,Caminade AM,Majoral JP,Alant J,Midha R(2013)Doxycycline-regulated GDNF expression promotes axonal regeneration and functional recovery in transected peripheral nerve.J Control Release 172:841-851.
Shan BE,Zhang JY,Li QX(2001)Human T cell and monocyte modulating activity of Rhizoma typhonii in vitro.Zhongguo Zhong Xi Yi Jie He Za Zhi 21:768-772.
Si HB,Zeng Y,Lu YR,Cheng JQ,Shen B(2017)Control-released basic fibroblast growth factor-loaded poly-lactic-co-glycolic acid microspheres promote sciatic nerve regeneration in rats.Exp Ther Med13:429-436.
Sun W,Sun C,Lin H,Zhao H,Wang J,Ma H,Chen B,Xiao Z,Dai J(2009)The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model.Biomaterials 30:4649-4656.
Tria MA,Fusco M,Vantini G,Mariot R(1994)Pharmacokinetics of nerve growth factor(NGF)following different routes of administration to adult rats.Exp Neurol 127:178-183.
Tsai CC,Lu MC,Chen YS,Wu CH,Lin CC(2003)Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration.Am J Chin Med 31:665-673.
Wang CZ,Chen YJ,Wang YH,Yeh ML,Huang MH,Ho ML,Liang JI,Chen CH(2014)Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.PLoS One 9:e103348.
Wang D,Li ZM,Zhao MJ,Xue RH,Xu H,Zhong LM(2018a)Neuroelectrophysiological characteristics of peripheral neuropathy in primary Sj?gren’s syndrome:study protocol for a prospective case series and pre-preliminary results.Asia Pac J Clin Trials Nerv Syst Dis 2018;3:68-73
Wang Z,Zhang P,Kou Y,Yin X,Han N,Jiang B(2013a)Hedysari extract improves regeneration after peripheral nerve injury by enhancing the amplification effect.PLos One 8:e67921.
Wang Z,Yang X,Zhang W,Zhang P,Jiang B(2018b)Tanshinone IIAattenuates nerve structural and functional damage induced by nerve crush injury in rats.PLoS One 13:e0202532.
Wang ZY,Zhang PX,Han N,Kou YH,Yin XF,Jiang BG(2013b)Effect of modified formula radix hedysari on the amplification effect during peripheral nerve regeneration.Evid Based Complement Alternat Med 2013:647982.
West CA,Davies KA,Hart AM,Wiberg M,Williams SR,Terenghi G(2007)Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury.Exp Neurol 203:22-33.
West CA,Ljungberg C,Wiberg M,Hart A(2013)Sensory neuron death after upper limb nerve injury and protective effect of repair:clinical evaluation using volumetric magnetic resonance imaging of dorsal root Ganglia.Neurosurgery 73:632-640.
Wojcikowski K,Gobe G(2014)Animal studies on medicinal herbs:predictability,dose conversion and potential value.Phytother Res28:22-27.
Wood MD,Gordon T,Kim H,Szynkaruk M,Phua P,Lafontaine C,Kemp SW,Shoichet MS,Borschel GH(2013)Fibrin gels containing GDNF microspheres increase axonal regeneration after delayed peripheral nerve repair.Regen Med 8:27-37.
Wood MD,Hunter D,Mackinnon SE,Sakiyama-Elbert SE(2010)Heparin-binding-affinity-based delivery systems releasing nerve growth factor enhance sciatic nerve regeneration.J Biomater Sci Polym Ed21:771-787.
Yang CC,Wang J,Chen SC,Jan YM,Hsieh YL(2015)Enhanced functional recovery from sciatic nerve crush injury through a combined treatment of cold-water swimming and mesenchymal stem cell transplantation.Neurol Res 37:816-826.
Yang JS(2010)Treatment for cold type facial paralysis by modified Qian Zheng San together with Ginger moxibustion.Zhongyi Zazhi7:71-74.
Yu H,Peng J,Guo Q,Zhang L,Li Z,Zhao B,Sui X,Wang Y,Xu W,Lu S(2009)Improvement of peripheral nerve regeneration in acellular nerve grafts with local release of nerve growth factor.Microsurgery29:330-336.
Zeng W,Rong M,Hu X,Xiao W,Qi F,Huang J,Luo Z(2014)Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor.PLoS One 9:e101300.
Zhang P,Zhang C,Kou Y,Yin X,Zhang H,Jiang B(2009)The histological analysis of biological conduit sleeve bridging rhesus monkey median nerve injury with small gap.Artif Cells Blood Substit Immobil Biotechnol 37:101-104.
Zhang P,Kou Y,Yin X,Wang Y,Zhang H,Jiang B(2011)The experimental research of nerve fibers compensation amplification innervation of ulnar nerve and musculocutaneous nerve in rhesus monkeys.Artif Cells Blood Substit Immobil Biotechnol 39:39-43.
Zhang P,Wang Z,Kou Y,Han N,Xu C,Yin X,Wang Y,Feng X(2014)Role of lumbricus extract in the nerve amplification effect during peripheral nerve regeneration.Am J Transl Res 6:876-885.
Zhang W,Zhou G,Gao Y,Zhou Y,Liu J,Zhang L,Long A,Zhang L,Tang P(2017)A sequential delivery system employing the synergism of EPO and NGF promotes sciatic nerve repair.Colloids Surf BBiointerfaces 159:327-336.
Zhang Y,Sun HM,He X,Wang YY,Gao YS,Wu HX,Xu H,Gong XG,Guo ZY(2013)Da-Bu-Yin-Wan and Qian-Zheng-San,two traditional Chinese herbal formulas,up-regulate the expression of mitochondrial subunit NADH dehydrogenase 1 synergistically in the mice model of Parkinson’s disease.J Ethnopharmacol 146:363-371.
Zhuang H,Bu S,Hua L,Darabi MA,Cao X,Xing M(2016)Gelatin-methacrylamide gel loaded with microspheres to deliver GDNFin bilayer collagen conduit promoting sciatic nerve growth.Int JNanomedicine 11:1383-1394.
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