丹酚酸B促进大鼠急性脊髓损伤修复及量效关系探讨

目的 研究腹腔注射丹酚酸B(Sal B)对大鼠急性脊髓损伤(SCI)模型的神经保护作用和促功能恢复作用,探讨Sal B在急性SCI治疗的应用价值,并探讨其量效关系. 方法参照Allen法制作SD大鼠T9脊髓节段急性损伤模型,腹腔注射Sal B或PBS液,按照注射液的不同分为4组:Sal B高剂量组(20 mg/kg组),Sal B中剂量组(10 mg/kg组),Sal B低剂量组(2 mg/kg组)和对照组(注射PBS液),每组12只.用比色法检测髓过氧化物酶活性;用免疫组织化学染色法检测损伤脊髓节段MMP-1、c-Fos抗体表达情况,用干湿重法评价的水肿程度,并采用后肢功能评分(BBB)评分评价10 d内大鼠的运动功能恢复情况. 结果损伤后4 h Sal B治疗组髓过氧化物酶活性下降,损伤后1 dHE染色切片显示SalB组治疗后局部组织损伤减轻,炎性细胞浸润数量减少,损伤后1d免疫组化染色结果显示,Sal B治疗组比对照组MMP-1表达减少,c-Fos表达下调;Sal B治疗组水肿程度轻于对照组,从SCI后第7天起,SalB组高剂量组(20 mg/kg组)和对照组之间的BBB评分有显著性差异(P<0.05).各指标改善情况与Sal B剂量呈正相关性. 结论 Sal B可减轻大鼠SCI后的组织损伤,下调损伤相关因子MMP-1和c-Fos的表达,降低损伤局部髓过氧化物酶活性,减轻组织水肿,并能促进损伤大鼠的功能恢复.

Salvianolic acid B reduces acute spinal cord injury and promotes the motor function recovery in rats with spinal contusion

Objective To investigate the effect of salvianolic acid B (Sal B) against the secondary spinal cord injury and on the motor function recovery in rats with contusive spind cord injury (SCI). Methods Forty-eight rats with contusive SCI received intraperitoneal injections of Sal B at different doses (2, 10, and 20 mg/kg, n=12) or PBS as control (n=12). Myeloperoxidase (MPO) activity in the spinal cord was determined using colorimetric method 4 h after SCI. Immunohistochemical staining was used to detect the expressions of matrix metallopeptidase 1 (MMP-1) and the cellular proto-oncogene c-Fos 1 d after SCI. The water content in the injured segment of the spinal cord was estimated 3 days atter SCI, and the BBB scores were used to assess the motor function recovery 10 days after SCI. Results High-dose (20 mg/kg) Sal B treatment significantly reduced the MPO activity in comparison with that in the control group (P<0.05). A statistical difference in the BBB scores was noted between the Sal B-treated and control rats 14 days after the treatment (P<0.05). The spinal cord levels of MMP-1 and c-Fos were significantly reduced in high-dose Sal B-treated rats as compared with those in the control rats. Edema in the injured spinal cord was significantly alleviated in high-dose Sal B group in comparison with that in the control group (P<0.05). The BBB scores also differed significantly between the high-dose Sal B and control groups 7 days after the treatment (P<0.05). The improvements of the all the indexes showed positive correlations to the dose ofSal B administered. Conclusion Sal B can alleviate the secondary neural tissue injuries following SCI by attenuating MPO activity, lowering the expressions of MMP-1 and c-Fos and reducing the water content in the injured spinal cord. Sal B also promotes the recovery of limb motor function in rats following SCI.