牛磺熊去氧胆酸对大鼠急性脊髓损伤后的神经保护作用及其对caspase-12表达的影响
Neuroprotective effects and impact on caspase-12 expression of tauroursodeoxycholic acid after acute spinal cord injury in rats.
作者信息
Dong Yi, Miao Lei, Hei Long, Lin Leilei, Ding Huiqiang
机构信息
Ningxia Medical University Yinchuan 750004, P. R. China.
Department of Spinal Surgery, General Hospital of Ningxia Medical University Yinchuan 750004, P. R. China.
出版信息
Int J Clin Exp Pathol. 2015 Dec 1;8(12):15871-8. eCollection 2015.
OBJECTIVE
To observe the effects of tauroursodeoxycholic acid (TUDCA) on nerve function after acute spinal cord injury (SCI) in rats, observe its effect on neuronal apoptosis and caspase-12 expression levels, and investigate the underlying mechanism.
METHODS
We used a modified Allen's weight-drop trauma method to establish a rat acute SCI model. The rats were randomly divided into three groups: group A (sham surgery group), group B (DMSO control group) and group C (TUDCA treatment group), with 36 rats in each group. At one minute and at 24 hours after successfully establishing the model, rats in group C received an intraperitoneal injection of TUDCA (200 mg/kg), while rats in group B received an equal amount of DMSO at the same time points. At 24 hours, three days, and five days after injury, a modified Tarlov scoring method and Rivlin's oblique plate test were used to evaluate rat spinal cord nerve function recovery. Animals were sacrificed at 24 hours, three days, and five days after injury. Specimens were obtained from the center of the injury sites; the pathological changes in spinal cord tissue were observed after hematoxylin-eosin (HE) staining; apoptosis was detected using the TUNEL method, and the expression of caspase-12 was measured at the protein level using immunohistochemistry and Western blots.
RESULTS
Group C differed significantly from group B in Tarlov scores and the oblique table test as early as 24 hours after the injury (P < 0.05). The TUNEL assay test results showed that neurons underwent apoptosis after SCI, which peaked at 24 hours. The ratios of apoptotic cells in group C were significantly lower than those in group B at 24 hours, three days, and five days after injury (P < 0.01). The immunohistochemistry and Western blot results showed that the caspase-12 expression levels of group C were lower than those of group B at 24 hours, three days, and five days after injury (P < 0.05).
CONCLUSION
TUDCA can inhibit the expression of caspase-12 in rat neurons after SCI, reduce cell apoptosis, and exert neuroprotective effects on rat secondary nerve injuries after SCI.
目的
观察牛磺熊去氧胆酸（TUDCA）对大鼠急性脊髓损伤（SCI）后神经功能的影响，观察其对神经元凋亡及半胱天冬酶 - 12表达水平的作用，并探讨其潜在机制。
方法
采用改良的Allen重物坠落创伤法建立大鼠急性SCI模型。将大鼠随机分为三组：A组（假手术组）、B组（二甲基亚砜对照组）和C组（TUDCA治疗组），每组36只。成功建立模型后1分钟及24小时，C组大鼠腹腔注射TUDCA（200mg/kg），B组大鼠在相同时间点注射等量的二甲基亚砜。在损伤后24小时、3天和5天，采用改良的Tarlov评分法和Rivlin斜板试验评估大鼠脊髓神经功能恢复情况。在损伤后24小时、3天和5天处死动物。从损伤部位中心获取标本；苏木精 - 伊红（HE）染色后观察脊髓组织的病理变化；采用TUNEL法检测细胞凋亡，采用免疫组织化学和蛋白质印迹法在蛋白质水平检测半胱天冬酶 - 12的表达。
结果
早在损伤后24小时，C组在Tarlov评分和斜板试验方面与B组有显著差异（P < 0.05）。TUNEL检测结果显示，SCI后神经元发生凋亡，在24小时达到峰值。损伤后24小时、3天和第5天，C组凋亡细胞比例显著低于B组（P < 0.01）。免疫组织化学和蛋白质印迹结果显示，损伤后24小时、3天和5天，C组半胱天冬酶 - 12表达水平低于B组（P < 0.05）。
结论
TUDCA可抑制大鼠SCI后神经元中半胱天冬酶 - 12的表达，减少细胞凋亡，对大鼠SCI后的继发性神经损伤发挥神经保护作用。
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