槲皮素对大鼠脊髓损伤的保护作用及机制探讨

Protective effects of quercetin on spinal cord injury in rats and its mechanism

目的探讨槲皮素对大鼠急性脊髓损伤的保护作用及其可能机制。方法将72只雌性SD大鼠随机分为模型组(SCI组)、槲皮素组(Que组)和假手术组(Sham组),每组各24只。采用改良Allen's打击法建立脊髓损伤模型,术后评估大鼠后肢运动功能(BBB评分),酶联免疫吸附试验(Elisa)检测脊髓组织匀浆髓过氧化物酶(myeloperoxidase,MPO)活性、脂质过氧化产物(malonydialdehyde,MDA)含量及超氧化物歧化酶(superoxide dismutase,SOD)活性,取血清检测肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素10(IL-10)含量。HE染色观察脊髓组织的病理变化,全血细胞分析检测血液白细胞水平变化。结果与模型组相比,槲皮素组大鼠脊髓损伤后6 h脊髓组织MPO含量由(65.5±12.3)nmol/mg降至(42.2±10.3)nmol/mg,MDA含量由(62.9±2.7)U/g降至(50.3±1.8)U/g,SOD水平由(212.4±10.3)U/mg升至(310.6±11.3)U/mg,血清TNF-α水平由(398.1±7.4)pg/ml降至(284.4±7.6)pg/ml,血清IL-6水平由(359.1±20.9)pg/ml降至(242.9±5.2)pg/ml,血清IL-10水平由(288.3±4.8)pg/ml升至(347.9±5.9)pg/ml,全血白细胞计数由(6.6±1.2)/视野降至(3.4±0.8)/视野,脊髓损伤后14 d时BBB评分由6.7±0.4升至9.1±0.7,差异均有统计学意义(P<0.05)。光镜下脊髓组织损伤程度降低。结论槲皮素对大鼠急性脊髓损伤具有保护作用,其机制可能是通过抑制炎性因子从而调节炎症反应及自由基而实现的。

Objective To investigate the protective effects of quercetin on spinal cord injury model of rats and its potential mechanism. Methods Totally 72 adult SD rats were randomly divided into three groups： sham group（n=24）, spinal cord injury（SCI） group（n=24） and quercetin（Que） group（n=24）. Model of spinal cord injury was established by modified Allen＇s assay. From first day after injury, motor function of rats＇ hind limb was evaluated by BBB（Basso Beattie and Bresnahan） scores. Content of myeloperoxidase（MPO）, malondialdehyde（MDA）, superoxide dismutase（SOD） in spinal cord tissue and levels of tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6）, interleukin-10（IL-10） in serum were determined by Elisa and white blood cell（WBC） count was evaluated by whole blood cell analysis. Pathological changes of spinal cord tissues were observed with HE staining. Results Compared with model group, the content of MPO in injured spinal cord at 6 h after injury in Que group decreased from（65.5±12.3） nmol/mg to（42.2±10.3） nmol/mg, MDA levels decreased from（62.9±2.7） U/g to（50.3±1.8） U/g, TNF-α levels in serum decreased from（398.1±7.4） pg/ml to（284.4±7.6） pg/ml, IL-6 levels decreased from（359.1±20.9） pg/ml to（242.9±5.2） pg/ml, and WBC counts（cells per field of view） decreased from（6.6±1.2） to（3.4±0.8）, while SOD activity increased from（212.4±10.3） U/mg to（310.6±11.3） U/mg, IL-10 levels increased from（288.3±4.8） pg/ml to（347.9±5.9） pg/ml（P〈0.05）. Compared with SCI group, BBB scores improved significantly from（6.7±0.4） to（9.1±0.7） at 14 d after injury in Que group（P〈0.05）. The pathological injury of spinal cord was relieved in Que group. Conclusion Quercetin administration results in the improvement of motor function after spinal cord injury. Its potential mechanism may be related with its effect on attenuating the recruitment of neutrophils to the injury site and lowering the content of MPO, MDA released in the injured tissue is likely to decrease the extent of secondary spinal cord injury.