丹参注射液对大鼠急性脊髓损伤后运动功能的作用及机制
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摘要
目的
(1)观察丹参注射液对大鼠急性脊髓损伤后运动功能的作用。
(2)探讨丹参注射液对大鼠急性脊髓损伤后运动功能的作用机制。
方法
1.动物造模、分组及干预方法
(1)动物造模
SD雄性大鼠144只,麻醉后俯卧位固定于手术台上,消毒后以T11为中心取后正中切口,咬除T10～T12椎板和棘突,用硬塑料片保护T10和T12脊髓,只暴露T11脊髓。采用改良Alleni去致伤脊髓：以10g不锈钢杆自三维立体定向仪上经套筒自由坠落4cm,撞击Tll脊髓,然后移去不锈钢杆,打击区脊髓硬脊膜下可见充血,观察到鼠尾痉挛性摆动,双下肢及躯体痉挛收缩,示造模成功。另选取SD雄性大鼠48只作为假手术组,采用上述手术方法,不撞击脊髓。
(2)分组144造模大鼠,随机分为观察组、对照组和SCI组,每组各48只,3组又各分为造模后1、3、7及14天组,每组12只。
(3)干预方法观察组：于造模后1h给予丹参注射液1.78mL/kg/天,腹腔内注射,每天1次,按存活时间分别注射1、3、7、14天。对照组：采用大剂量冲击疗法,于造模后1h腹腔注射甲基强的松龙30mg/kg,45min后按5.4mg/kg/h计算23h总量,分4次腹腔注射。假手术组和SCI组：不进行任何干预。分别于手术后1天、3天、7天、14天,分组分批取材。
2.实验指标检测
(1)各组大鼠一般状态比较
(2)行为学评分采用改良Rivlin斜板法评分来评价大鼠的脊髓功能。
(3)组织病理学观察光学显微镜下观察脊髓造模后1天、3天、7天、14天的细胞结构变化。
(4)原位杂交检测包括胶质细胞源性神经营养因子(GDNF)、乙酰胆碱转化酶(ChAT)、突触体素(synaptophysin).突触素(synapsin)、突触结合蛋白I(sytI)。
3.统计学处理
将所得数据用SPSS11.0版统计软件进行统计。
结果
1.各组大鼠一般状态比较
损伤1天后,各组大鼠毛发散乱,后肢无法运动,呼吸较浅,饮食减少,尿失禁或尿潴留。损伤3天后观察组与对照组毛色散乱,后肢能轻微活动,但不能支撑爬行,SCI组后肢毛色干枯、散乱,无任何活动,均呼吸较浅、饮食减少、尿失禁或尿潴留。损伤7天后,观察组和对照组动物毛色变润泽、整齐,后肢活动增强,无法支撑爬行,呼吸正常,饮食有所增加,尿失禁或尿潴留有所改善,SCI组无明显变化。损伤14天后观察组和对照组动物毛色润泽、整齐,后肢活动增强,稍可支撑爬行,呼吸正常,饮食接近正常,排尿趋于正常,SCI组毛发散乱,后肢轻微活动,呼吸接近正常,饮食有所增加,尿失禁或尿潴留有所改善。
2.行为学评分
各组损伤前斜板试验临界角比较,差异无统计学意义(P>0.05)。造模后1天,观察组斜板试验临界角低于治疗前及对照组同期(P<0.01)；造模后3天,观察组斜板试验临界角与造模后1天比较,差异无统计学意义(P>0.05);造模后7天,观察组斜板试验临界角高于造模后3天及SCI组同期(P<0.01),低于对照组(P<0.05)；造模后14天,观察组斜板试验临界角高于造模后7天及SCI组同期(P<0.01,P<0.05),与对照组无显著差异(P>0.05)。
3.组织病理学改变
脊髓造模后1天,SCI组脊髓损伤灰质区明显出血、水肿,部分神经元变性坏死；观察组和对照组部分神经元坏死,但出血、水肿较轻。造模后3天,SCI组脊髓损伤灰质区仍明显出血、水肿,神经元坏死增多；观察组出血、水肿减轻,神经元坏死稍增多；对照组出血、水肿减轻,神经元坏死增多。造模后7天、14天,SCI组脊髓损伤灰质区出血、水肿减轻：观察组和对照组出血、水肿均明显减轻。
4.原位杂交检测结果
(1)胶质细胞源性神经营养因子(GDNF)表达造模后1天,观察组GDNF阳性产物吸光度值低于对照组同期(P<0.05),高于SCI组同期(P<0.01)；造模后3天,高于造模后1天及SCI组同期(P<0.01,P<0.05),低于对照组同期(P<0.05)；造模后7天,与造模后3天及对照组同期无显著差异(P>0.05,P>0.05),高于SCI组同期(P<0.01)；造模后14天,与造模后7天及对照组同期无显著差异(P>0.05,P>0.05),高于SCI组同期(P<0.01)。
(2)乙酰胆碱转化酶(ChAT)表达造模后1天,观察组的ChAT阳性产物吸光度值低于对照组(P<0.01),与SCI组无显著差异(P>0.05)；在造模后3天、7天的乙酰胆碱转化酶阳性产物吸光度值低于对照组(P<0.05),高于SCI组(P<0.01)；在造模后14天与对照组无显著差异(P>0.05),高于SCI组(P<0.01)。
(3)突触体素(synaptophysin)表达造模后1天、3天,观察组的synaptophysin阳性产物吸光度值与对照组和SCI组无显著差异(P>0.05),在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P>0.05)。
(4)突触素I(synapsinI)表达造模后1天、3天,观察组的synaptophysin吸光度值与对照组和SCI组无显著差异(P>0.05),在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P>0.05)。
(5)突触结合蛋白I(synaptotagmin, SytI)表达观察组在造模后1天sytI阳性产物吸光度值与对照组和SCI组无显著差异(P>0.05)；造模后3天低于对照组(P<0.05),高于SCI组(P<0.01)；在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P<0.05)。
结论
(1)丹参注射液对急性脊髓损伤运动功能具有保护作用
(2)丹参注射液对急性脊髓损伤灰质的保护机制：可能通过促进脊髓灰质突触体素、突触素Ⅰ、突触结合蛋白Ⅰ、胶质细胞源性神经营养因子、乙酰胆碱转化酶合成,加快脊髓灰质突触的功能恢复。
Objective
To observe effect of Danshen injections on Acetylcholine transferase, Glial cell line-derived neurotrophic factor, synaptophysin, synapsinI and Synaptic adhesion proteins I in the gray matter of rat after acute spinal cord injury. To deduce the mechanism about the effect of Salvia miltiorrhiza on acute spinal cord injury.
Methods
1.Grouping and making rat models with acute spinal cord injury:144Male SD rats were randomly divided into observation group, control group and SCI group (48in each group) Spinal cords of rats in these groups were injured with Modified Allen method. Other spinal cords of48rats in the sham group were not injured in addition to the same surgical procedure as that in SCI group.
2. Delivery method
(1) Observation group:Salvia miltiorrhiza injection was injected into rats'abdominal cavity in one hour (Once a day, and respectively injected for one time, three times, seven times, fourteen times according to different groups)
(2) Control group:Used large dose of shock therapy, methylprednisolone was injected into rats' abdominal cavity with30mg/kg first, and then respectively injected into rats' abdominal cavity in0.5hour, lhour,2hour and4hour with4.5*23/4mg/kg.
3.Indexes detection
(1)Behavioral score:Assessing the spinal cord function with inclined plate method improved by Rivlin
(2) Histopathology:With optical microscope, observating the change in cell structure in1days、3days、7days and14days after acute spinal injury.
(3)hybridization in situ:Including acetylcholine transferase, glial cell line-derived neurotrophic factor, synaptophysin, synapsinI and synaptic adhesion proteinsl.
4. Statistical analysis:The data will be calculated with SPSS11.0.
Results
1. Behavioral score:The critical angle of inclined plane test was significantly reduced in observation group and control group on the first day, the third day after modeling. There was not significant difference between observation group and control group(P>0.05). There was a slight rebound in critical angle on the seventh day and the fourteenth day after modeling. The critical angle in control group was greater than that of the observation group on the seventh day(P<0.05). There was not significant difference between observation group and control group in the critical angle of inclined plane test on the fourteenth day(P>0.05).
2. Histopathology:Bleeding, edema, thin nissl bodies in cytoplasm were found in damage zone of gray matter of observation group and control group on the first day after modeling, with part of denatured and necrotic neurons. Bleeding and edema were reduced in observation group on the third day, with slightly increased neuronal necrosis. Bleeding and edema were reduced in control group on the third day, with increased neuronal necrosis. Bleeding and edema were significantly reduced in damage zone on the seventh day and the fourteenth day, with thick nissl bodies in cytoplasm.
4. Glial cell line-derived neurotrophic factor(GDNF):The absorbance value of GDNF positive products in observation group was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the first day after modeling. It was less than that of control group(P<0.05), but more than that of SCI group(P<0.05)on the third day. It was not significant difference from control group(P>0.05), but more than that of SCI group(P<0.01)on the seventh day and the fourteenth day(P>0.05).
3. Acetylcholine-converting enzyme(ChAT):The absorbance value of ChAT positive products in observation group was less than that of control group(P<0.01), but not significant difference from SCI group(P>0.05)on the first day after modeling. It was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the third day and the seventh day. It was more than that of SCI group(P<0.01), but was not significant difference from control group(P>0.05)on the fourteenth day.
5. synaptophysin:The absorbance value of synaptophysin positive products in observation group was not significant difference compared with control group and SCI group on the first day and the third day after modeling(P>0.05). It was more than that of SCI group(P<0.01), but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
6. synapsin I:The absorbance value of synapsin I positive products in observation group was not significant difference compared with control group and SCI group on the first day and the third day after modeling(P>0.05). It was more than that of SCI group(P<0.01),but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
7. Synaptic adhesion proteins I (syt I):The absorbance value of syt I positive products in observation group was not significant difference compared with control group and SCI group on the first day after modeling(P>0.05). It was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the third day. It was more than that of SCI group(P<0.01), but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
Conclusion
1. Animal model in this experimentation was repeatable, reliable and controllable.
2. Protection of Salvia for spinal cord gray matter after acute spinal cord injury
Salvia could increase ChAT, GDNF, synaptophysin, synapsinI and sytI in spinal cord gray matter after acute spinal cord injury. The mechanisms maybe that Salvia increases the active of ChAT to restore the motor function of spinal cord gray matter, and increases the active of associated protein in synaptic to promote the transfer of nerve impulses.
(1)观察丹参注射液对大鼠急性脊髓损伤后运动功能的作用。
(2)探讨丹参注射液对大鼠急性脊髓损伤后运动功能的作用机制。
方法
1.动物造模、分组及干预方法
(1)动物造模
SD雄性大鼠144只,麻醉后俯卧位固定于手术台上,消毒后以T11为中心取后正中切口,咬除T10～T12椎板和棘突,用硬塑料片保护T10和T12脊髓,只暴露T11脊髓。采用改良Alleni去致伤脊髓：以10g不锈钢杆自三维立体定向仪上经套筒自由坠落4cm,撞击Tll脊髓,然后移去不锈钢杆,打击区脊髓硬脊膜下可见充血,观察到鼠尾痉挛性摆动,双下肢及躯体痉挛收缩,示造模成功。另选取SD雄性大鼠48只作为假手术组,采用上述手术方法,不撞击脊髓。
(2)分组144造模大鼠,随机分为观察组、对照组和SCI组,每组各48只,3组又各分为造模后1、3、7及14天组,每组12只。
(3)干预方法观察组：于造模后1h给予丹参注射液1.78mL/kg/天,腹腔内注射,每天1次,按存活时间分别注射1、3、7、14天。对照组：采用大剂量冲击疗法,于造模后1h腹腔注射甲基强的松龙30mg/kg,45min后按5.4mg/kg/h计算23h总量,分4次腹腔注射。假手术组和SCI组：不进行任何干预。分别于手术后1天、3天、7天、14天,分组分批取材。
2.实验指标检测
(1)各组大鼠一般状态比较
(2)行为学评分采用改良Rivlin斜板法评分来评价大鼠的脊髓功能。
(3)组织病理学观察光学显微镜下观察脊髓造模后1天、3天、7天、14天的细胞结构变化。
(4)原位杂交检测包括胶质细胞源性神经营养因子(GDNF)、乙酰胆碱转化酶(ChAT)、突触体素(synaptophysin).突触素(synapsin)、突触结合蛋白I(sytI)。
3.统计学处理
将所得数据用SPSS11.0版统计软件进行统计。
结果
1.各组大鼠一般状态比较
损伤1天后,各组大鼠毛发散乱,后肢无法运动,呼吸较浅,饮食减少,尿失禁或尿潴留。损伤3天后观察组与对照组毛色散乱,后肢能轻微活动,但不能支撑爬行,SCI组后肢毛色干枯、散乱,无任何活动,均呼吸较浅、饮食减少、尿失禁或尿潴留。损伤7天后,观察组和对照组动物毛色变润泽、整齐,后肢活动增强,无法支撑爬行,呼吸正常,饮食有所增加,尿失禁或尿潴留有所改善,SCI组无明显变化。损伤14天后观察组和对照组动物毛色润泽、整齐,后肢活动增强,稍可支撑爬行,呼吸正常,饮食接近正常,排尿趋于正常,SCI组毛发散乱,后肢轻微活动,呼吸接近正常,饮食有所增加,尿失禁或尿潴留有所改善。
2.行为学评分
各组损伤前斜板试验临界角比较,差异无统计学意义(P>0.05)。造模后1天,观察组斜板试验临界角低于治疗前及对照组同期(P<0.01)；造模后3天,观察组斜板试验临界角与造模后1天比较,差异无统计学意义(P>0.05);造模后7天,观察组斜板试验临界角高于造模后3天及SCI组同期(P<0.01),低于对照组(P<0.05)；造模后14天,观察组斜板试验临界角高于造模后7天及SCI组同期(P<0.01,P<0.05),与对照组无显著差异(P>0.05)。
3.组织病理学改变
脊髓造模后1天,SCI组脊髓损伤灰质区明显出血、水肿,部分神经元变性坏死；观察组和对照组部分神经元坏死,但出血、水肿较轻。造模后3天,SCI组脊髓损伤灰质区仍明显出血、水肿,神经元坏死增多；观察组出血、水肿减轻,神经元坏死稍增多；对照组出血、水肿减轻,神经元坏死增多。造模后7天、14天,SCI组脊髓损伤灰质区出血、水肿减轻：观察组和对照组出血、水肿均明显减轻。
4.原位杂交检测结果
(1)胶质细胞源性神经营养因子(GDNF)表达造模后1天,观察组GDNF阳性产物吸光度值低于对照组同期(P<0.05),高于SCI组同期(P<0.01)；造模后3天,高于造模后1天及SCI组同期(P<0.01,P<0.05),低于对照组同期(P<0.05)；造模后7天,与造模后3天及对照组同期无显著差异(P>0.05,P>0.05),高于SCI组同期(P<0.01)；造模后14天,与造模后7天及对照组同期无显著差异(P>0.05,P>0.05),高于SCI组同期(P<0.01)。
(2)乙酰胆碱转化酶(ChAT)表达造模后1天,观察组的ChAT阳性产物吸光度值低于对照组(P<0.01),与SCI组无显著差异(P>0.05)；在造模后3天、7天的乙酰胆碱转化酶阳性产物吸光度值低于对照组(P<0.05),高于SCI组(P<0.01)；在造模后14天与对照组无显著差异(P>0.05),高于SCI组(P<0.01)。
(3)突触体素(synaptophysin)表达造模后1天、3天,观察组的synaptophysin阳性产物吸光度值与对照组和SCI组无显著差异(P>0.05),在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P>0.05)。
(4)突触素I(synapsinI)表达造模后1天、3天,观察组的synaptophysin吸光度值与对照组和SCI组无显著差异(P>0.05),在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P>0.05)。
(5)突触结合蛋白I(synaptotagmin, SytI)表达观察组在造模后1天sytI阳性产物吸光度值与对照组和SCI组无显著差异(P>0.05)；造模后3天低于对照组(P<0.05),高于SCI组(P<0.01)；在造模后7天、14天高于SCI组(P<0.01),与对照组无显著差异(P<0.05)。
结论
(1)丹参注射液对急性脊髓损伤运动功能具有保护作用
(2)丹参注射液对急性脊髓损伤灰质的保护机制：可能通过促进脊髓灰质突触体素、突触素Ⅰ、突触结合蛋白Ⅰ、胶质细胞源性神经营养因子、乙酰胆碱转化酶合成,加快脊髓灰质突触的功能恢复。
Objective
To observe effect of Danshen injections on Acetylcholine transferase, Glial cell line-derived neurotrophic factor, synaptophysin, synapsinI and Synaptic adhesion proteins I in the gray matter of rat after acute spinal cord injury. To deduce the mechanism about the effect of Salvia miltiorrhiza on acute spinal cord injury.
Methods
1.Grouping and making rat models with acute spinal cord injury:144Male SD rats were randomly divided into observation group, control group and SCI group (48in each group) Spinal cords of rats in these groups were injured with Modified Allen method. Other spinal cords of48rats in the sham group were not injured in addition to the same surgical procedure as that in SCI group.
2. Delivery method
(1) Observation group:Salvia miltiorrhiza injection was injected into rats'abdominal cavity in one hour (Once a day, and respectively injected for one time, three times, seven times, fourteen times according to different groups)
(2) Control group:Used large dose of shock therapy, methylprednisolone was injected into rats' abdominal cavity with30mg/kg first, and then respectively injected into rats' abdominal cavity in0.5hour, lhour,2hour and4hour with4.5*23/4mg/kg.
3.Indexes detection
(1)Behavioral score:Assessing the spinal cord function with inclined plate method improved by Rivlin
(2) Histopathology:With optical microscope, observating the change in cell structure in1days、3days、7days and14days after acute spinal injury.
(3)hybridization in situ:Including acetylcholine transferase, glial cell line-derived neurotrophic factor, synaptophysin, synapsinI and synaptic adhesion proteinsl.
4. Statistical analysis:The data will be calculated with SPSS11.0.
Results
1. Behavioral score:The critical angle of inclined plane test was significantly reduced in observation group and control group on the first day, the third day after modeling. There was not significant difference between observation group and control group(P>0.05). There was a slight rebound in critical angle on the seventh day and the fourteenth day after modeling. The critical angle in control group was greater than that of the observation group on the seventh day(P<0.05). There was not significant difference between observation group and control group in the critical angle of inclined plane test on the fourteenth day(P>0.05).
2. Histopathology:Bleeding, edema, thin nissl bodies in cytoplasm were found in damage zone of gray matter of observation group and control group on the first day after modeling, with part of denatured and necrotic neurons. Bleeding and edema were reduced in observation group on the third day, with slightly increased neuronal necrosis. Bleeding and edema were reduced in control group on the third day, with increased neuronal necrosis. Bleeding and edema were significantly reduced in damage zone on the seventh day and the fourteenth day, with thick nissl bodies in cytoplasm.
4. Glial cell line-derived neurotrophic factor(GDNF):The absorbance value of GDNF positive products in observation group was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the first day after modeling. It was less than that of control group(P<0.05), but more than that of SCI group(P<0.05)on the third day. It was not significant difference from control group(P>0.05), but more than that of SCI group(P<0.01)on the seventh day and the fourteenth day(P>0.05).
3. Acetylcholine-converting enzyme(ChAT):The absorbance value of ChAT positive products in observation group was less than that of control group(P<0.01), but not significant difference from SCI group(P>0.05)on the first day after modeling. It was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the third day and the seventh day. It was more than that of SCI group(P<0.01), but was not significant difference from control group(P>0.05)on the fourteenth day.
5. synaptophysin:The absorbance value of synaptophysin positive products in observation group was not significant difference compared with control group and SCI group on the first day and the third day after modeling(P>0.05). It was more than that of SCI group(P<0.01), but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
6. synapsin I:The absorbance value of synapsin I positive products in observation group was not significant difference compared with control group and SCI group on the first day and the third day after modeling(P>0.05). It was more than that of SCI group(P<0.01),but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
7. Synaptic adhesion proteins I (syt I):The absorbance value of syt I positive products in observation group was not significant difference compared with control group and SCI group on the first day after modeling(P>0.05). It was less than that of control group(P<0.05), but more than that of SCI group(P<0.01)on the third day. It was more than that of SCI group(P<0.01), but was not significant difference compared with control group(P>0.05)on the seventh day and the fourteenth day.
Conclusion
1. Animal model in this experimentation was repeatable, reliable and controllable.
2. Protection of Salvia for spinal cord gray matter after acute spinal cord injury
Salvia could increase ChAT, GDNF, synaptophysin, synapsinI and sytI in spinal cord gray matter after acute spinal cord injury. The mechanisms maybe that Salvia increases the active of ChAT to restore the motor function of spinal cord gray matter, and increases the active of associated protein in synaptic to promote the transfer of nerve impulses.
引文
[1]Xiong Y, Rabchevsky AG, Hall ED.Role of peroxynitrite in secondary oxidative damage after spinal cord injury[J].Neurochem,2007,100(3):639-649.
[2]Doble A. The role of excitotoxicity in neurodegenerative disease:implications for therapy[J]. Pharmacol Ther,1999,81:163-221.
[3]Osterholm LJ, Mathews JG. Altered norepinephrine metabolism following experimental spinal cord injury[J]. Part 1 Relationship to hemorrhagic necrosis and post-wounding neurological deficits. J Neurosurg,1972,36(3):386-394.
[4]CashaS, Yu WR, Fehlings MG.FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury[J]. Exp Neurol,2005,196:390-400.
[5]Wagner FC Jr, Dohrmann GJ, Bucy PC. Histopathology of transitory traumatic paraplegia in the monkey[J]Neurosurg,1971,35(2):272-276.
[6]Hall ED.Wolf DL,Braughler JM. Effects of a single large dose of methylprednisolone sodium succinct on experimental posttraumatic spinal cord schema:Dose-reponse and time action analysis. J Neurosurg,1984,61(7):124-130.
[7]Osterholm LJ,Mathews JG. Altered norepinephrine metabolism following experimental spinal cord injury. Part 1. Relationship to hemorrhagic necrosis and post-wounding neurological deficits[J]. Neurosurg,1972,36(3):386-394.
[8]Mvorcia B. New view of spinal cord injury. Science,1996,274:466.
[9]秦川,主编.实验动物学.人民卫生山版社,203,2010年08月,第1版.
[10]Allen AR.Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocaion of spinal colum[J]. JAMA,1911,57:878-880.
[11]Tralov IM,Kinger H.Spinal cord compression studies[J].Arch Neuro psychiatry,1954,70:813-819.
[12]王颖,曹斌,王开友.神经节苷脂对大鼠急性脊髓损伤后运动诱发电位和后肢运动功能的影响[J].山东医药,2008,48(10)：28-29.
[13]承欧梅,钟士江,吴秀书,等.纳洛酮治疗非外伤性急性脊髓损伤的疗效观察[J].中国综合临床,2004,20(12)：1077-1078.
[14]Cayli SR, Kocak A, Yilmaz U, et al. Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury[J].Eur Spine J,2004,13(8):724-732.
[15]王钢,刘世清,陶海鹰.丹参对兔脊髓损伤段钙、水含量改变的保护作用[J].武汉大学学报(医版),2002,23(1)：51-52.
[16]唐莉,邓力.丹参注射液对血管内皮细胞低氧损伤的保护作用[J].时珍国医国药,2011,22(5)：1112-1114.
[17]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响[J].中国中西医结合杂志,2003,23(6)：167-169.
[18]余永桂,张功礼,施永彦,等.丹参注射液椎管内局部灌注对急性脊髓损伤的保护作用[J].中华实验外科杂志,2004,21(8)：993-994.
[19]杨春壮,刘长发,杨春佳.丹参注射液治疗急性脊髓损伤疗效观察[J].中医信药息.2003,20(6)：36.
[20]刘德明,刘曾旭,王文敏,等.复方丹参注射液对大鼠脊髓损伤后肢体运动功能的影响[J].中药药理与临床,2002,18(2)：6-8.
[21]宋跃明,沈彬丹参对牵张性脊髓损伤的防治作用[J].中华创伤杂志,1998,14(6)：389-392.
[22]Gale K Kerasidis H.Spinal cord contusion in the rat.Behavial of functional neurological impairment[J]. Exp Neurol,1985,88(1):123-131.
[23]Lin LF,Doherty DH,Lile JD,et al.GDNF:a glial cell line derived neurotrophic factor for midbrain dopaminergic neurons[J].Science,1993,260(5111):1130-1132.
[24]Lucini C,Maruccio L,Facello B,et al.Cellular localization of GDNF and its GFRalphal/RET receptor complex in the developing pancreas of cat[J].J Anat,2008,213(5):565-572.
[25]Yoong LF,Wan G,Too HP,et al. GDNF induced cell signaling and neurite outgrowths are differentially mediated by GFRalphal isoforms[J].Mol Cell Neurosci,2009,41(4):464-473.
[26]Sharma HS. Post traumatic application of brain derived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96:329-334.
[27]Grumbles RM,Sesodia S,Wood PM,et al.Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons[J].J Neuropathol Exp Neurol,2009,68(7):736-746.
[28]吴淑玉,王丽琴,宋学琴等.2034对体外运动神经元和感觉神经元的影响[J].中国应用生理学杂志,2004,20(1)：5-6.
[29]Paratcha G,Ledda F.GDNFandGFR α:a versatile molecular complex for developing neurons[J].Trends Neurosci,2008,31(8):384-391.
[30]Juger, Juger WG, CNTF and GDNF, but not NT-4, support corticol spinal motor meuron growth via direct mechanism[J]. Neuroreport,1998,9(16):3749-3754.
[31]袁源.胶质细胞源性神经营养因子与脊髓损伤修复[J].国外医学神经病学神经外科学分册,2003,30(1)：39-42.
[32]蒋朝勇,王静成,杨建东.胶质细胞源性神经营养因子与脊髓损伤治疗[J].国际骨科学杂志,2011,32(5)：302-303.
[33]Gomes CA, Simoes PF, Canas PM, et al. GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A receptors[J]. Neurochem,2009,108(1):1208-1019.
[34]Miquel B, Pineda JR, Cristina S, et al, Induction of GABAergic phenotype in a neural stem cell line for transplantation in an excitotoxic model of Huntington's disease[J]. Exp Neurol,2004,190(1):42-58.
[35]Sharma HS. Post traumatic application of brain derived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96:329-334.
[36]Pedersen LM, Jacobsen LM, Mollerup S, et al. Spinal cord long-term poteniation(LTP) is associated dorsal horn gene expression of IL-lbeta, GDNF and lnos[J].Eur Pain,2010,14(3):255-260.
[37]Hosaka M, Hammer RE, Sudhof TC (1999). A phospho-switch controls the dynamic association of synapsin with synaptic vesicles[J]. Neuron 24 (2):377-87.
[38]Fiumara F, Onofri F, Benfenati F, et al. (2001). Intracellular injcction of synapsin 1 induces transmitter release in Cl neurons of Helix pomatia contacting a wrong target[J]. Neuroscience 104(1):271-280.
[39]Stefani G, Onofri F, Valtorta F, Vaccaro P, Greengard P, et al. Kinetic analysis of the phosphorylation-dependent interactions of synapsin I with rat brain synaptic vesicles[J]. JOURNAL OF PHYSIOLOGY-LONDON.1997 NOV 1; 504 (3):501-515.
[40]Takei Y, Harada A, Takeda S, Kobayashi K, Terada S, et al. Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system[J]JOURNAL OF CELL BIOLOGY.1995 DEC;131(6):1789-1800.
[41]宿宝贵,潘三强,韩辉,等.大鼠海马结构在空间辨别性学习记忆时突触素表达的变化[J].中国病理生理杂志,2000,]6(5)：421-423.
[42]Molteni R, Ying Z, Gomez-Pinilla F. Differenlial effects of acute and chronic exercise on plasticity related genes in the rat hippocampus revealed by micmamy[J].Eur J Neursci,2002,16:1]07-1116.
[43]Wu A, Molteni R, Ying Z, et al. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain derived neurotrophic factor[J].Neuroscience,2003,119(2):365-375.
[44]Chin L,Li L, Ferreila A. Impairent of axonal development and synaptogenesis in hippocampal neurons of synpasin I-deficient mice[J].Pro Nat] Acad Sci USA,1995,92:9230-9234.
[45]李吕琪,刘丹,卢大华等.小鼠坐骨神经损伤后内源性BDNF对脊髓前角运动神经元内突触素mRNA表达的调节[J].神经解剖学杂志,2005,21(4)345-349.
[46]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervousA basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[47]Sudhof T C, Lottspeich F, Greengard P, et al. A synaptophysin aptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions[J]. Science,1987,238(4830):1142-1144.
[48]Phelan P,Gordon Weeks PR.Widespread distribution of synaptophysin aptophysin,a synaptophysin aptic vesicle glycoprotein,in growing neurites and growth cones[J].Eur J Neurosci,1992,4:1180-1190.
[49]Ovtscharoff W, Bergmann M, Marpurze-Pouey B, et al. Ontogeny of synaptophysin aptophysin and synaptophysin aptoporin in the central nervous system:differential expression in striatal neurons and their afferents during development[J]. Dev Brain Res,1993,72:219.
[50]Navone F, Jahn R, Gioia G, et al. Protein P38:an integral membraneprotein specific for small vesicles of neurons and neuroendocrine cells[J]. Cell Biol,1986,103:2511.
[51]Bergmann M, hr G, yerhofer A, al. Expression of synaptophysin aptohpyson during the prenatal development of the rat spinal cord:correlation with basic differentiation processes of neurons[J]. Neuroscience,1991,42(2):569.
[52]Tarsa L, Goda Y. synaptophysin aptophysin regulates activity-dependent synaptophysin ase formation in cultured hippocampal neurons[J]. Proc Natl Acad Sci USA,2002,99(2):1012-1016.
[53]Janz R, sudhof TC, Hammer RE, et al. Essention rolesin synaptophysin aptic plascity for synaptophysin aptogyrin I and synaptophysin aptophysin [J]. Neuron,1999,24(3):687-700.
[54]黄如训,张艳,方燕南,等.大鼠脑梗死后运动功能可塑性物质基础及发生机制[J].中华医学杂志,2000,80(10)：769-772..
[55]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervousA basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[56]丰岩清,郭云良,梁秀龄.神经生长因子对脑缺血再灌注大鼠突触素表达的影响[J].中国动脉硬化杂志,2001,9(2)：123-125.
[57]Chapman ER. How does synaptotagmin trigger neurotransmitter release? [J].Annu Rev Biochem, 2008,77:615-641.
[48]Matthew WD, Tsavaler L,Reichardt LF. Identification of a synaptic vesicle-specific protein with a wide tissue distribution in neuronal and neurosecretory tissue[J].Cell Biol,1981,91(1):257-269.
[59]Sudhof TC. Synaptotagmins:why so many[J]. Biol Cell,2002,277 (10):7629-7632.
[60]Fernandez-Chacon R.Konigstorfer A.Gerber S H,et al. Synaptotagmin I functions as a calcium regulator of release probability[J]. Nature,2001,410(6824):41-49.
[61]Josep Rizo, Christian Rosenmund. Synaptic vesicle fusion[J]. Nat Struct Mol Biol,2008,15:665-674.
[62]王静,汪青松突触结合蛋白-1.突触结合蛋白-1与学习记忆的研究进展[J].神经解剖学杂志.2011,27(2)：35-37.
[63]Adolfen B.Littleton J T. Genetic and molecular analysis of the synaptotagmin family[J]. Cell Mol Life Sci,2001,58:393-402.
[64]朱美财,乙酰胆碱酯酶的结构和功能研究进展[J].生物化学与生物物理进展,1992,19(5)：338.
[65]Dong H, Xiang YY, Farchi N, et al. Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons[J]. J Neurosci,2004,24(41):8950-8960.
[66]Zhang XJ, Yan L, Zhao Q,et al. Induction of aoetylcholnesterase expression during apoptosis in various cell types[J]Cell Death Differ,2002,9(8):790-800.
[67]王新家,孔抗美,吴珊鹏等.减压脊髓神经恢复分子机制的研究[J].中华实验外科杂志,2005,22(8)：978-980.
[68]余世春,琚小龙,段广勋.丹参的化学成分和药理活性研究概况(综述)[J].安徽卫生职业技术学院学报,2002,1(2)：43.
[70]刘世清,王钢,陶海鹰,等.丹参对脊髓损伤后血清钙、镁、锌、铜含量的影响[J].中国中医骨伤科杂志,2001,9(3)：13-15.
[71]欧喜超,杨朝阳,刘玉军,等.大鼠脊髓损伤后运动功能的恢复及前角运动神经元功能的改变[J].中国康复与实践,2008,14(3)：231-233.
[72]宋跃明,沈彬.丹参对牵张性脊髓损伤的防治作用[J].中华刨伤杂志,1998.14(6)：389-392.
[73]周文辉.复方丹参滴丸治疗冠心病心绞痛160例疗效观察[J].中华临床医药杂志,2001,13(8)：1137.
[74]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响[J].中围中西医结合杂志,2003,23：167-169.
[75]王钢,刘世清,王志林.丹参对急性脊髓损伤患者血液流变学的影响.[J]中国微循环,2004,8(2)：101-102.
[76]黄迪南.复方丹参注射液对巨噬细胞NO合成的影响[J].中国老年杂志,1999,19(1)：41-42.
[77]Sharma HS. Post traumatic application of brainderived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96 (2):329-334.
[78]Sharma HS. Post traumatic application of brainderived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96 (2):329-334.
[79]YatoY, FujimuraY, NakamuraM,etal. Decreased choline acetyltransferase activity in the murine spinal cord motoneurons under chronicmechanical compression[J]. Spinal Cord,1997,35:729-734.
[80]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervous:A basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[81]刘世清,赵东明,王海斌,等.复方丹参对大鼠脊髓损伤后细胞凋亡的影响[J].中国临床康复,2004,8(29)：6434-6436.
[82]刘德明,王文敏,刘曾旭,等.复方丹参注射液对大鼠急性脊髓损伤后神经再生的影响[J].四川解剖学杂志,2002,10(4)：200-201.
[1]许翔,江曙.脊髓损伤后自由基变化及丹参对自由基影响的实验研究[J].中国骨伤,1999,12(5)：16-18.
[2]倪江东,丁仁奎,吕国华,等.中药丹参注射液对兔脊髓损伤的影响[J].医科大学学报,2002,27(6)：507-508.
[3]宋跃明,沈彬.丹参对牵张性脊髓损伤的防治作用[J].中华刨伤杂志,1998,14(6)：389-392
[4]马永刚,刘世清,彭吴,等.复方丹参对大鼠实验性脊髓损伤的保护作用[J].山东中医药大学学报,2002,26(3)：216-218.
[5]余永桂,张功礼,施永彦,等.丹参注射液椎管内局部灌注对急性脊髓损伤的保护作用[J].中华实验外科杂志,2004 21(8)：993-994.
[6]赵正据,欧阳静萍.复方丹参保护大鼠脊髓继发性损伤的实验研究[J].成宁医学院学报,2002,(16)4：238-241.
[7]刘曾旭,刘德明,王文敏,等.复方丹参对脊髓损伤大鼠一氧化氮合酶神经元的影响[J].解剖学杂志,2004,27(4)：401-404.
[8]郭岱琦,王大平,杨雷,等.肖建德丹参对脊髓损伤早期NO含量影响的实验研究[J].中西医结合脑血管病杂志,2004,7(2)：408-408.
[9]刘世清,赵东明,王海斌,等.复方丹参对大鼠脊髓损伤后细胞凋亡的影响[J].中国临床康复,2004,8(29)：6434-6436.
[10]胡培高,孔抗美,王新家,等.复方丹参和甲基强的松龙联合治疗对大鼠急性损伤脊髓细胞凋亡及NOS表达的影响[J].实用医学杂,2005,21(17)：1873-1875.
[11]蒋赞利,茅祖斌,吴小涛,等.复方丹参注射液对脊髓损伤大鼠细胞凋亡的影响[J].中国临床康复,2003,7(23)：3182-3183.
[12]Ferguson AR, Christensen RN, Gensel JC, et al. Cell death after spinal cord injury is exacerbated by rapid TNF alpha-induced trafficking of Glur2-lacking AMPARs to the plasma membrane[J].Neurosci:2008,28(44):11391-11400.
[13]田伟,孔岚,王征美,等.丹参舒颈丸对颈髓受压模型大鼠病理变化的影响[J].中国康复理论与实践,2009,15(5)：436-438.
[14]周文辉.复方丹参滴丸治疗冠心病心绞痛160例疗效观察[J].中华临床医药杂志,2001,13(8)：1137.
[15]韩晶研,秋叶保忠,崛江义则,等.复方丹参滴丸及其主要成分丹参、丹参素、三七、三七总皂苷对微循化障碍的多靶点改善作用[C].第三届全国复方丹参滴丸学术会议论文集,2005：15-22.
[16]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响.中国中西医结合杂志,2003,23：167-169.
[17]王钢,刘世清,王志林.丹参对急性脊髓损伤患者血液流变学的影响[J].中国微循环,2004,8(2)：101-102.
[18]刘德明,王文敏,刘曾旭,等.复方月参注射液对大鼠急性脊髓损伤后神经再生的影响[J].四川解剖学杂志,2002,10(4)：200-201.
[19]Miller RH. Building bridges with astrocytes for spinal cord repair. J Biol,2006,5:6-7.
[20]魏福堂,夏春林,张洪涛.复方月参对大鼠脊髓急性损伤后神经丝蛋白及胶质原纤维酸性蛋白表达的影响[J].中华实验外科杂志,2007,24(1)：112.
[21]王磊,刘云会.复方丹参对大鼠脊髓损伤后髓磷酯碱性蛋自基因表达的影响[J].中医药学刊,2006,24(8)：1537-1539.
[22]Demopoulos HB, et al. The free radical pathology and the microcirculation in the major central nervous system disorders[J]. Acca Physiol scand [Suppl].1980,(492):91.
[23]Young W. et al. Extracellular calcium ionic activity in Experimental spinal cord contusion[J].Brain Res,1982,253:105.
[24]Hall ED, et al. Effects Of intravenous methyprednisolone on spinal cord lipid peroxidation and(Na+-K+)-ATPase activity[J]. Dose-response analysis during an hour after contusion injury in the cat. J. Neurosurg,1982, (57):247.
[25]王钢,刘世清,陶海鹰.丹参对兔脊髓损伤段钙、水含量改变的保护作用[J].武汉大学学报(医学版),2002,23(1)：51-52.
[26]刘世清,王钢,陶海鹰,等.丹参对脊髓损伤后血清钙、镁、锌、铜含量的影响[J].中国中医骨伤科杂志,2001,9(3)：13-15.
[27]欧喜超,杨朝阳,刘玉军,等.大鼠脊髓损伤后运动功能的恢复及前角运动神经元功能的改变[J].中国康复与实践,2008,14(3)：231-233.
[28]刘德明,刘曾旭,王文敏,等.复方丹参注射液对大鼠脊髓损伤后肢体运动功能的影响[J].中药药理与临床,2002,18(2)：6-8.
[29]吴江,高建新,刘克敬,等.实验性大鼠脊髓损伤后运动能力及病理学变化的研究[J].山东大学学报(医学版),2006,44(3)：231-234.
[30]杨春壮,刘长发,杨春佳.丹参注射液治疗急性脊髓损伤疗效观察[J],中医信药息.2003,20(6)：36.
[2]Doble A. The role of excitotoxicity in neurodegenerative disease:implications for therapy[J]. Pharmacol Ther,1999,81:163-221.
[3]Osterholm LJ, Mathews JG. Altered norepinephrine metabolism following experimental spinal cord injury[J]. Part 1 Relationship to hemorrhagic necrosis and post-wounding neurological deficits. J Neurosurg,1972,36(3):386-394.
[4]CashaS, Yu WR, Fehlings MG.FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury[J]. Exp Neurol,2005,196:390-400.
[5]Wagner FC Jr, Dohrmann GJ, Bucy PC. Histopathology of transitory traumatic paraplegia in the monkey[J]Neurosurg,1971,35(2):272-276.
[6]Hall ED.Wolf DL,Braughler JM. Effects of a single large dose of methylprednisolone sodium succinct on experimental posttraumatic spinal cord schema:Dose-reponse and time action analysis. J Neurosurg,1984,61(7):124-130.
[7]Osterholm LJ,Mathews JG. Altered norepinephrine metabolism following experimental spinal cord injury. Part 1. Relationship to hemorrhagic necrosis and post-wounding neurological deficits[J]. Neurosurg,1972,36(3):386-394.
[8]Mvorcia B. New view of spinal cord injury. Science,1996,274:466.
[9]秦川,主编.实验动物学.人民卫生山版社,203,2010年08月,第1版.
[10]Allen AR.Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocaion of spinal colum[J]. JAMA,1911,57:878-880.
[11]Tralov IM,Kinger H.Spinal cord compression studies[J].Arch Neuro psychiatry,1954,70:813-819.
[12]王颖,曹斌,王开友.神经节苷脂对大鼠急性脊髓损伤后运动诱发电位和后肢运动功能的影响[J].山东医药,2008,48(10)：28-29.
[13]承欧梅,钟士江,吴秀书,等.纳洛酮治疗非外伤性急性脊髓损伤的疗效观察[J].中国综合临床,2004,20(12)：1077-1078.
[14]Cayli SR, Kocak A, Yilmaz U, et al. Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury[J].Eur Spine J,2004,13(8):724-732.
[15]王钢,刘世清,陶海鹰.丹参对兔脊髓损伤段钙、水含量改变的保护作用[J].武汉大学学报(医版),2002,23(1)：51-52.
[16]唐莉,邓力.丹参注射液对血管内皮细胞低氧损伤的保护作用[J].时珍国医国药,2011,22(5)：1112-1114.
[17]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响[J].中国中西医结合杂志,2003,23(6)：167-169.
[18]余永桂,张功礼,施永彦,等.丹参注射液椎管内局部灌注对急性脊髓损伤的保护作用[J].中华实验外科杂志,2004,21(8)：993-994.
[19]杨春壮,刘长发,杨春佳.丹参注射液治疗急性脊髓损伤疗效观察[J].中医信药息.2003,20(6)：36.
[20]刘德明,刘曾旭,王文敏,等.复方丹参注射液对大鼠脊髓损伤后肢体运动功能的影响[J].中药药理与临床,2002,18(2)：6-8.
[21]宋跃明,沈彬丹参对牵张性脊髓损伤的防治作用[J].中华创伤杂志,1998,14(6)：389-392.
[22]Gale K Kerasidis H.Spinal cord contusion in the rat.Behavial of functional neurological impairment[J]. Exp Neurol,1985,88(1):123-131.
[23]Lin LF,Doherty DH,Lile JD,et al.GDNF:a glial cell line derived neurotrophic factor for midbrain dopaminergic neurons[J].Science,1993,260(5111):1130-1132.
[24]Lucini C,Maruccio L,Facello B,et al.Cellular localization of GDNF and its GFRalphal/RET receptor complex in the developing pancreas of cat[J].J Anat,2008,213(5):565-572.
[25]Yoong LF,Wan G,Too HP,et al. GDNF induced cell signaling and neurite outgrowths are differentially mediated by GFRalphal isoforms[J].Mol Cell Neurosci,2009,41(4):464-473.
[26]Sharma HS. Post traumatic application of brain derived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96:329-334.
[27]Grumbles RM,Sesodia S,Wood PM,et al.Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons[J].J Neuropathol Exp Neurol,2009,68(7):736-746.
[28]吴淑玉,王丽琴,宋学琴等.2034对体外运动神经元和感觉神经元的影响[J].中国应用生理学杂志,2004,20(1)：5-6.
[29]Paratcha G,Ledda F.GDNFandGFR α:a versatile molecular complex for developing neurons[J].Trends Neurosci,2008,31(8):384-391.
[30]Juger, Juger WG, CNTF and GDNF, but not NT-4, support corticol spinal motor meuron growth via direct mechanism[J]. Neuroreport,1998,9(16):3749-3754.
[31]袁源.胶质细胞源性神经营养因子与脊髓损伤修复[J].国外医学神经病学神经外科学分册,2003,30(1)：39-42.
[32]蒋朝勇,王静成,杨建东.胶质细胞源性神经营养因子与脊髓损伤治疗[J].国际骨科学杂志,2011,32(5)：302-303.
[33]Gomes CA, Simoes PF, Canas PM, et al. GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A receptors[J]. Neurochem,2009,108(1):1208-1019.
[34]Miquel B, Pineda JR, Cristina S, et al, Induction of GABAergic phenotype in a neural stem cell line for transplantation in an excitotoxic model of Huntington's disease[J]. Exp Neurol,2004,190(1):42-58.
[35]Sharma HS. Post traumatic application of brain derived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96:329-334.
[36]Pedersen LM, Jacobsen LM, Mollerup S, et al. Spinal cord long-term poteniation(LTP) is associated dorsal horn gene expression of IL-lbeta, GDNF and lnos[J].Eur Pain,2010,14(3):255-260.
[37]Hosaka M, Hammer RE, Sudhof TC (1999). A phospho-switch controls the dynamic association of synapsin with synaptic vesicles[J]. Neuron 24 (2):377-87.
[38]Fiumara F, Onofri F, Benfenati F, et al. (2001). Intracellular injcction of synapsin 1 induces transmitter release in Cl neurons of Helix pomatia contacting a wrong target[J]. Neuroscience 104(1):271-280.
[39]Stefani G, Onofri F, Valtorta F, Vaccaro P, Greengard P, et al. Kinetic analysis of the phosphorylation-dependent interactions of synapsin I with rat brain synaptic vesicles[J]. JOURNAL OF PHYSIOLOGY-LONDON.1997 NOV 1; 504 (3):501-515.
[40]Takei Y, Harada A, Takeda S, Kobayashi K, Terada S, et al. Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system[J]JOURNAL OF CELL BIOLOGY.1995 DEC;131(6):1789-1800.
[41]宿宝贵,潘三强,韩辉,等.大鼠海马结构在空间辨别性学习记忆时突触素表达的变化[J].中国病理生理杂志,2000,]6(5)：421-423.
[42]Molteni R, Ying Z, Gomez-Pinilla F. Differenlial effects of acute and chronic exercise on plasticity related genes in the rat hippocampus revealed by micmamy[J].Eur J Neursci,2002,16:1]07-1116.
[43]Wu A, Molteni R, Ying Z, et al. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain derived neurotrophic factor[J].Neuroscience,2003,119(2):365-375.
[44]Chin L,Li L, Ferreila A. Impairent of axonal development and synaptogenesis in hippocampal neurons of synpasin I-deficient mice[J].Pro Nat] Acad Sci USA,1995,92:9230-9234.
[45]李吕琪,刘丹,卢大华等.小鼠坐骨神经损伤后内源性BDNF对脊髓前角运动神经元内突触素mRNA表达的调节[J].神经解剖学杂志,2005,21(4)345-349.
[46]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervousA basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[47]Sudhof T C, Lottspeich F, Greengard P, et al. A synaptophysin aptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions[J]. Science,1987,238(4830):1142-1144.
[48]Phelan P,Gordon Weeks PR.Widespread distribution of synaptophysin aptophysin,a synaptophysin aptic vesicle glycoprotein,in growing neurites and growth cones[J].Eur J Neurosci,1992,4:1180-1190.
[49]Ovtscharoff W, Bergmann M, Marpurze-Pouey B, et al. Ontogeny of synaptophysin aptophysin and synaptophysin aptoporin in the central nervous system:differential expression in striatal neurons and their afferents during development[J]. Dev Brain Res,1993,72:219.
[50]Navone F, Jahn R, Gioia G, et al. Protein P38:an integral membraneprotein specific for small vesicles of neurons and neuroendocrine cells[J]. Cell Biol,1986,103:2511.
[51]Bergmann M, hr G, yerhofer A, al. Expression of synaptophysin aptohpyson during the prenatal development of the rat spinal cord:correlation with basic differentiation processes of neurons[J]. Neuroscience,1991,42(2):569.
[52]Tarsa L, Goda Y. synaptophysin aptophysin regulates activity-dependent synaptophysin ase formation in cultured hippocampal neurons[J]. Proc Natl Acad Sci USA,2002,99(2):1012-1016.
[53]Janz R, sudhof TC, Hammer RE, et al. Essention rolesin synaptophysin aptic plascity for synaptophysin aptogyrin I and synaptophysin aptophysin [J]. Neuron,1999,24(3):687-700.
[54]黄如训,张艳,方燕南,等.大鼠脑梗死后运动功能可塑性物质基础及发生机制[J].中华医学杂志,2000,80(10)：769-772..
[55]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervousA basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[56]丰岩清,郭云良,梁秀龄.神经生长因子对脑缺血再灌注大鼠突触素表达的影响[J].中国动脉硬化杂志,2001,9(2)：123-125.
[57]Chapman ER. How does synaptotagmin trigger neurotransmitter release? [J].Annu Rev Biochem, 2008,77:615-641.
[48]Matthew WD, Tsavaler L,Reichardt LF. Identification of a synaptic vesicle-specific protein with a wide tissue distribution in neuronal and neurosecretory tissue[J].Cell Biol,1981,91(1):257-269.
[59]Sudhof TC. Synaptotagmins:why so many[J]. Biol Cell,2002,277 (10):7629-7632.
[60]Fernandez-Chacon R.Konigstorfer A.Gerber S H,et al. Synaptotagmin I functions as a calcium regulator of release probability[J]. Nature,2001,410(6824):41-49.
[61]Josep Rizo, Christian Rosenmund. Synaptic vesicle fusion[J]. Nat Struct Mol Biol,2008,15:665-674.
[62]王静,汪青松突触结合蛋白-1.突触结合蛋白-1与学习记忆的研究进展[J].神经解剖学杂志.2011,27(2)：35-37.
[63]Adolfen B.Littleton J T. Genetic and molecular analysis of the synaptotagmin family[J]. Cell Mol Life Sci,2001,58:393-402.
[64]朱美财,乙酰胆碱酯酶的结构和功能研究进展[J].生物化学与生物物理进展,1992,19(5)：338.
[65]Dong H, Xiang YY, Farchi N, et al. Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons[J]. J Neurosci,2004,24(41):8950-8960.
[66]Zhang XJ, Yan L, Zhao Q,et al. Induction of aoetylcholnesterase expression during apoptosis in various cell types[J]Cell Death Differ,2002,9(8):790-800.
[67]王新家,孔抗美,吴珊鹏等.减压脊髓神经恢复分子机制的研究[J].中华实验外科杂志,2005,22(8)：978-980.
[68]余世春,琚小龙,段广勋.丹参的化学成分和药理活性研究概况(综述)[J].安徽卫生职业技术学院学报,2002,1(2)：43.
[70]刘世清,王钢,陶海鹰,等.丹参对脊髓损伤后血清钙、镁、锌、铜含量的影响[J].中国中医骨伤科杂志,2001,9(3)：13-15.
[71]欧喜超,杨朝阳,刘玉军,等.大鼠脊髓损伤后运动功能的恢复及前角运动神经元功能的改变[J].中国康复与实践,2008,14(3)：231-233.
[72]宋跃明,沈彬.丹参对牵张性脊髓损伤的防治作用[J].中华刨伤杂志,1998.14(6)：389-392.
[73]周文辉.复方丹参滴丸治疗冠心病心绞痛160例疗效观察[J].中华临床医药杂志,2001,13(8)：1137.
[74]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响[J].中围中西医结合杂志,2003,23：167-169.
[75]王钢,刘世清,王志林.丹参对急性脊髓损伤患者血液流变学的影响.[J]中国微循环,2004,8(2)：101-102.
[76]黄迪南.复方丹参注射液对巨噬细胞NO合成的影响[J].中国老年杂志,1999,19(1)：41-42.
[77]Sharma HS. Post traumatic application of brainderived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96 (2):329-334.
[78]Sharma HS. Post traumatic application of brainderived neurotrophic factor and glia derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96 (2):329-334.
[79]YatoY, FujimuraY, NakamuraM,etal. Decreased choline acetyltransferase activity in the murine spinal cord motoneurons under chronicmechanical compression[J]. Spinal Cord,1997,35:729-734.
[80]Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in nervous:A basis for the pathophysiology of traumatic and ischemic central nervous system injury[J]. Neurosurgery.1996,38:1176.
[81]刘世清,赵东明,王海斌,等.复方丹参对大鼠脊髓损伤后细胞凋亡的影响[J].中国临床康复,2004,8(29)：6434-6436.
[82]刘德明,王文敏,刘曾旭,等.复方丹参注射液对大鼠急性脊髓损伤后神经再生的影响[J].四川解剖学杂志,2002,10(4)：200-201.
[1]许翔,江曙.脊髓损伤后自由基变化及丹参对自由基影响的实验研究[J].中国骨伤,1999,12(5)：16-18.
[2]倪江东,丁仁奎,吕国华,等.中药丹参注射液对兔脊髓损伤的影响[J].医科大学学报,2002,27(6)：507-508.
[3]宋跃明,沈彬.丹参对牵张性脊髓损伤的防治作用[J].中华刨伤杂志,1998,14(6)：389-392
[4]马永刚,刘世清,彭吴,等.复方丹参对大鼠实验性脊髓损伤的保护作用[J].山东中医药大学学报,2002,26(3)：216-218.
[5]余永桂,张功礼,施永彦,等.丹参注射液椎管内局部灌注对急性脊髓损伤的保护作用[J].中华实验外科杂志,2004 21(8)：993-994.
[6]赵正据,欧阳静萍.复方丹参保护大鼠脊髓继发性损伤的实验研究[J].成宁医学院学报,2002,(16)4：238-241.
[7]刘曾旭,刘德明,王文敏,等.复方丹参对脊髓损伤大鼠一氧化氮合酶神经元的影响[J].解剖学杂志,2004,27(4)：401-404.
[8]郭岱琦,王大平,杨雷,等.肖建德丹参对脊髓损伤早期NO含量影响的实验研究[J].中西医结合脑血管病杂志,2004,7(2)：408-408.
[9]刘世清,赵东明,王海斌,等.复方丹参对大鼠脊髓损伤后细胞凋亡的影响[J].中国临床康复,2004,8(29)：6434-6436.
[10]胡培高,孔抗美,王新家,等.复方丹参和甲基强的松龙联合治疗对大鼠急性损伤脊髓细胞凋亡及NOS表达的影响[J].实用医学杂,2005,21(17)：1873-1875.
[11]蒋赞利,茅祖斌,吴小涛,等.复方丹参注射液对脊髓损伤大鼠细胞凋亡的影响[J].中国临床康复,2003,7(23)：3182-3183.
[12]Ferguson AR, Christensen RN, Gensel JC, et al. Cell death after spinal cord injury is exacerbated by rapid TNF alpha-induced trafficking of Glur2-lacking AMPARs to the plasma membrane[J].Neurosci:2008,28(44):11391-11400.
[13]田伟,孔岚,王征美,等.丹参舒颈丸对颈髓受压模型大鼠病理变化的影响[J].中国康复理论与实践,2009,15(5)：436-438.
[14]周文辉.复方丹参滴丸治疗冠心病心绞痛160例疗效观察[J].中华临床医药杂志,2001,13(8)：1137.
[15]韩晶研,秋叶保忠,崛江义则,等.复方丹参滴丸及其主要成分丹参、丹参素、三七、三七总皂苷对微循化障碍的多靶点改善作用[C].第三届全国复方丹参滴丸学术会议论文集,2005：15-22.
[16]胡俊勇,刘世敬,杨远良,等.丹参对大鼠脊髓损伤后脊髓血流量及运动功能的影响.中国中西医结合杂志,2003,23：167-169.
[17]王钢,刘世清,王志林.丹参对急性脊髓损伤患者血液流变学的影响[J].中国微循环,2004,8(2)：101-102.
[18]刘德明,王文敏,刘曾旭,等.复方月参注射液对大鼠急性脊髓损伤后神经再生的影响[J].四川解剖学杂志,2002,10(4)：200-201.
[19]Miller RH. Building bridges with astrocytes for spinal cord repair. J Biol,2006,5:6-7.
[20]魏福堂,夏春林,张洪涛.复方月参对大鼠脊髓急性损伤后神经丝蛋白及胶质原纤维酸性蛋白表达的影响[J].中华实验外科杂志,2007,24(1)：112.
[21]王磊,刘云会.复方丹参对大鼠脊髓损伤后髓磷酯碱性蛋自基因表达的影响[J].中医药学刊,2006,24(8)：1537-1539.
[22]Demopoulos HB, et al. The free radical pathology and the microcirculation in the major central nervous system disorders[J]. Acca Physiol scand [Suppl].1980,(492):91.
[23]Young W. et al. Extracellular calcium ionic activity in Experimental spinal cord contusion[J].Brain Res,1982,253:105.
[24]Hall ED, et al. Effects Of intravenous methyprednisolone on spinal cord lipid peroxidation and(Na+-K+)-ATPase activity[J]. Dose-response analysis during an hour after contusion injury in the cat. J. Neurosurg,1982, (57):247.
[25]王钢,刘世清,陶海鹰.丹参对兔脊髓损伤段钙、水含量改变的保护作用[J].武汉大学学报(医学版),2002,23(1)：51-52.
[26]刘世清,王钢,陶海鹰,等.丹参对脊髓损伤后血清钙、镁、锌、铜含量的影响[J].中国中医骨伤科杂志,2001,9(3)：13-15.
[27]欧喜超,杨朝阳,刘玉军,等.大鼠脊髓损伤后运动功能的恢复及前角运动神经元功能的改变[J].中国康复与实践,2008,14(3)：231-233.
[28]刘德明,刘曾旭,王文敏,等.复方丹参注射液对大鼠脊髓损伤后肢体运动功能的影响[J].中药药理与临床,2002,18(2)：6-8.
[29]吴江,高建新,刘克敬,等.实验性大鼠脊髓损伤后运动能力及病理学变化的研究[J].山东大学学报(医学版),2006,44(3)：231-234.
[30]杨春壮,刘长发,杨春佳.丹参注射液治疗急性脊髓损伤疗效观察[J],中医信药息.2003,20(6)：36.