改良大鼠尾椎间盘退变模型的建立
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摘要
目的：
改变固定椎体来避免营养障碍对尾椎间盘退变造成的影响并建立改良大鼠尾椎间盘退变模型。
方法：
第一部分：4月龄雌性SD大鼠24只,随机分为对照组和实验组,实验组鼠尾安装外固定支架,对照组不安装。Co7和Co10椎体各交叉并平行打入两根克氏针,克氏针垂直鼠尾且与矢状面呈45°,安装外固定支架,术后两组大鼠每日给与肌注青霉素(共计5天)及酒精滴孔以预防感染。两组分别于术前全部及术后1、2、3个月各随机抽取4只大鼠,取标本前行MRI检查并测量MEANS值,影像学检查后取出Co7～Co10椎间盘组织进行HE染色和Ⅰ型和Ⅱ型胶原免疫组化染色。
第二部分：动物及分组、手术操作过程、影像学检查、标本留取及病理学检查同第一部分,实验组大鼠鼠尾安装外固定支架并加压3N,对照组仅安装外固定支架不加压。
结果：
第一部分：对照组Co7～8、Co8～9和Co9～10髓核T2像上信号无明显变化,MEANS无明显变化；实验组T2像上Co7～8和Co9～10髓核信号随时间增加而降低,Co8～9无明显变化,Co7～8和Co9～10髓核MEANS值与对照组相比减少,术后3个月时两组之间MEANS值差异均有统计学意义,Co8～9髓核MEANS值术后3个月时比对照组略减少,但两组之间无统计学意义。对照组术后病理学上无明显差异,髓核组织中可见较多脊索细胞和类软骨细胞,细胞排列均匀,纤维环各层排列整齐,纤维环与髓核之间的过渡区较宽,实验组Co7～8和Co9～10在术后3个月时可见髓核细胞减少,纤维环排列尚规则,纤维环与髓核过渡区稍变窄,Co8～9无明显异常；对照组免疫组化染色显示髓核组织中Ⅰ型胶原和Ⅱ型胶原染色均呈较规整网状,实验组Co7～8和Co9～10在术后3个月时Ⅰ型胶原染色略加深,排列基本规则,Ⅱ型胶原染色正常,网状结构尚规则,Co8～9与对照组相比无明显异常。
第二部分：术后3个月时实验组椎间隙变窄,T2像上髓核信号明显降低,终板和髓核界限模糊,对照组无明显变化,实验组和对照组的MEANS值比较有统计学意义。实验组术后3个月时髓核细胞明显减少,出现退变坏死细胞,纤维环排列不规整,肿胀明显并呈结节样团样结构,出现裂隙及断裂,纤维环与髓核过渡区变窄明显变窄,对照组正常；实验组免疫组化染色显示髓核组织中Ⅰ型胶原染色较对照组深,同时Ⅱ型胶原染色较对照组浅,且形状不规则,网状结构破坏。
结论：
①采用外固定支架固定四节相邻尾椎及改变进针方向,从而避免椎体破坏和动静脉受压导致的椎间盘营养障碍,消除了营养障碍致椎间盘退变对异常应力致椎间盘退变的影响。②采用改良方法制作椎间盘退变模型获得成功,此模型为椎间盘退变的研究提供了较为满意的实验平台。
Objective:
①Rat caudal immobilized vertebrae were changed in order to avoid the nutritional effects of intervertebral disc degeneration.②Improved intervertebral disc degeneration model of rat caudal was established.
Methods:
PartⅠ:24 mature (4-month-old retired breeders) female Sprague-Dawley rats were divided into control and experimental groups. The apparatus was applied to the 7th and 10th caudal vertebrae of experimental group and the control group was not installed. Kirschner wire is perpendicular to the tail and leaving it with 45°angle of the sagittal. Intramuscular injection of penicillin and alcohol were used to prevent infection after surgery.4 rats each were randomly selected specimens of two groups at 1,2,3 months after surgery were taken the MRI examination and measured MEANS value. Purpose of intervertebral disc tissue was removed after the imaging examination and then examined pathologically.
PartⅡ:This part was basically the same with the first part. The apparatus was applied to the 7th and 10th caudal vertebrae of two groups. But it was compressed 3N of experimental group and the control group was not.
Results:
PartⅠ:The vertebral space of two groups were normal at 3 months after surgery. The signal of control group nucleus pulposus in T2 imaging did not change significantly. The signal of experimental group Co7～8 and Co9～10 nucleus pulposus in T2 imaging decreased with time increase and Co8～9 no significant changing. The MEANS value of Co7～8 and Co9～10 nucleus pulposus of experimental group compared with the control group decreased. There was significant statistically between the MEANS value of control group and experimental group at 3 month after surgery. The MEANS value of Co8～9 nucleus pulposus of experimental group at 3 months slightly decreased, but no statistical significance between two group. The nucleus pulposus in the control group had more uniform arrangement of notochord cells and chondroid cells and annulus layers arranged in neat rows. The Co7～8 and Co9～10 nucleus pulposus cells of experimental group reduced at 3 months after surgery and Co8～9 was normal. The collagen of typeⅠand typeⅡwere more regular mesh in the nucleus pulposus of control group. The collagen of typeⅠwas deep in the Co7～8 and Co9～10 nucleus pulposus of experimental group and Co8～9 was normal. The collagen of typeⅡhad not significant difference at 3 months after surgery.
PartⅡ:The vertebral space of experimental group was narrowing at 3 months after surgery. The signal of nucleus pulposus in T2 imaging significantly decreased and the boundary between endplate and nucleus pulposus were blurred. The MEANS value of experimental group and the control group were statistically significant. The nucleus pulposus cells of experimental group significantly reduced at 3 months after surgery and necrotic cells appeared. Annulus was obvious swelling and irregular arrangement. The transition region was narrowing between annulus and nucleus. Collagen typeⅠof nucleus pulposus in the experimental group showed depth staining than the control group and collagen typeⅡshowed shallow. The network structure was damaged. The control group did not change significantly.
Conclusion:
①Four adjacent caudal vertebraes were fixed with the external fixation apparatus and needle direction was changed in order to avoid the nutritional effects of intervertebral disc degeneration. In this study, the influence of nutritional disorder to disc degeneration had been resolved.②Intervertebral disc degeneration animal models had been successfully used to establish modified methods. The satisfactory experimental platform had been provided to the study of intervertebral disc degeneration. This method of developing the animal experiment offers model to study the degeneration of lumbar intervertebra disc.
改变固定椎体来避免营养障碍对尾椎间盘退变造成的影响并建立改良大鼠尾椎间盘退变模型。
方法：
第一部分：4月龄雌性SD大鼠24只,随机分为对照组和实验组,实验组鼠尾安装外固定支架,对照组不安装。Co7和Co10椎体各交叉并平行打入两根克氏针,克氏针垂直鼠尾且与矢状面呈45°,安装外固定支架,术后两组大鼠每日给与肌注青霉素(共计5天)及酒精滴孔以预防感染。两组分别于术前全部及术后1、2、3个月各随机抽取4只大鼠,取标本前行MRI检查并测量MEANS值,影像学检查后取出Co7～Co10椎间盘组织进行HE染色和Ⅰ型和Ⅱ型胶原免疫组化染色。
第二部分：动物及分组、手术操作过程、影像学检查、标本留取及病理学检查同第一部分,实验组大鼠鼠尾安装外固定支架并加压3N,对照组仅安装外固定支架不加压。
结果：
第一部分：对照组Co7～8、Co8～9和Co9～10髓核T2像上信号无明显变化,MEANS无明显变化；实验组T2像上Co7～8和Co9～10髓核信号随时间增加而降低,Co8～9无明显变化,Co7～8和Co9～10髓核MEANS值与对照组相比减少,术后3个月时两组之间MEANS值差异均有统计学意义,Co8～9髓核MEANS值术后3个月时比对照组略减少,但两组之间无统计学意义。对照组术后病理学上无明显差异,髓核组织中可见较多脊索细胞和类软骨细胞,细胞排列均匀,纤维环各层排列整齐,纤维环与髓核之间的过渡区较宽,实验组Co7～8和Co9～10在术后3个月时可见髓核细胞减少,纤维环排列尚规则,纤维环与髓核过渡区稍变窄,Co8～9无明显异常；对照组免疫组化染色显示髓核组织中Ⅰ型胶原和Ⅱ型胶原染色均呈较规整网状,实验组Co7～8和Co9～10在术后3个月时Ⅰ型胶原染色略加深,排列基本规则,Ⅱ型胶原染色正常,网状结构尚规则,Co8～9与对照组相比无明显异常。
第二部分：术后3个月时实验组椎间隙变窄,T2像上髓核信号明显降低,终板和髓核界限模糊,对照组无明显变化,实验组和对照组的MEANS值比较有统计学意义。实验组术后3个月时髓核细胞明显减少,出现退变坏死细胞,纤维环排列不规整,肿胀明显并呈结节样团样结构,出现裂隙及断裂,纤维环与髓核过渡区变窄明显变窄,对照组正常；实验组免疫组化染色显示髓核组织中Ⅰ型胶原染色较对照组深,同时Ⅱ型胶原染色较对照组浅,且形状不规则,网状结构破坏。
结论：
①采用外固定支架固定四节相邻尾椎及改变进针方向,从而避免椎体破坏和动静脉受压导致的椎间盘营养障碍,消除了营养障碍致椎间盘退变对异常应力致椎间盘退变的影响。②采用改良方法制作椎间盘退变模型获得成功,此模型为椎间盘退变的研究提供了较为满意的实验平台。
Objective:
①Rat caudal immobilized vertebrae were changed in order to avoid the nutritional effects of intervertebral disc degeneration.②Improved intervertebral disc degeneration model of rat caudal was established.
Methods:
PartⅠ:24 mature (4-month-old retired breeders) female Sprague-Dawley rats were divided into control and experimental groups. The apparatus was applied to the 7th and 10th caudal vertebrae of experimental group and the control group was not installed. Kirschner wire is perpendicular to the tail and leaving it with 45°angle of the sagittal. Intramuscular injection of penicillin and alcohol were used to prevent infection after surgery.4 rats each were randomly selected specimens of two groups at 1,2,3 months after surgery were taken the MRI examination and measured MEANS value. Purpose of intervertebral disc tissue was removed after the imaging examination and then examined pathologically.
PartⅡ:This part was basically the same with the first part. The apparatus was applied to the 7th and 10th caudal vertebrae of two groups. But it was compressed 3N of experimental group and the control group was not.
Results:
PartⅠ:The vertebral space of two groups were normal at 3 months after surgery. The signal of control group nucleus pulposus in T2 imaging did not change significantly. The signal of experimental group Co7～8 and Co9～10 nucleus pulposus in T2 imaging decreased with time increase and Co8～9 no significant changing. The MEANS value of Co7～8 and Co9～10 nucleus pulposus of experimental group compared with the control group decreased. There was significant statistically between the MEANS value of control group and experimental group at 3 month after surgery. The MEANS value of Co8～9 nucleus pulposus of experimental group at 3 months slightly decreased, but no statistical significance between two group. The nucleus pulposus in the control group had more uniform arrangement of notochord cells and chondroid cells and annulus layers arranged in neat rows. The Co7～8 and Co9～10 nucleus pulposus cells of experimental group reduced at 3 months after surgery and Co8～9 was normal. The collagen of typeⅠand typeⅡwere more regular mesh in the nucleus pulposus of control group. The collagen of typeⅠwas deep in the Co7～8 and Co9～10 nucleus pulposus of experimental group and Co8～9 was normal. The collagen of typeⅡhad not significant difference at 3 months after surgery.
PartⅡ:The vertebral space of experimental group was narrowing at 3 months after surgery. The signal of nucleus pulposus in T2 imaging significantly decreased and the boundary between endplate and nucleus pulposus were blurred. The MEANS value of experimental group and the control group were statistically significant. The nucleus pulposus cells of experimental group significantly reduced at 3 months after surgery and necrotic cells appeared. Annulus was obvious swelling and irregular arrangement. The transition region was narrowing between annulus and nucleus. Collagen typeⅠof nucleus pulposus in the experimental group showed depth staining than the control group and collagen typeⅡshowed shallow. The network structure was damaged. The control group did not change significantly.
Conclusion:
①Four adjacent caudal vertebraes were fixed with the external fixation apparatus and needle direction was changed in order to avoid the nutritional effects of intervertebral disc degeneration. In this study, the influence of nutritional disorder to disc degeneration had been resolved.②Intervertebral disc degeneration animal models had been successfully used to establish modified methods. The satisfactory experimental platform had been provided to the study of intervertebral disc degeneration. This method of developing the animal experiment offers model to study the degeneration of lumbar intervertebra disc.
引文
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