卡介苗通过抑制大鼠急性脊髓损伤中炎症级联反应保护脊髓的机制

Study on the mechanism of BCG vaccine to protect the spinal cord by inhibiting the inflammatory casccde in acute spinal cord injury in rats

目的探究卡介苗(BCG)对大鼠急性脊髓损伤(SCI)后炎症因子的影响。方法选取健康成年SD雄性大鼠72只,体重250~300 g,随机分为假手术组、模型组和BCG治疗组,各24只。假手术组仅行椎板切除,模型组和BCG治疗组均采用改良的Allen’S法制作脊髓损伤大鼠模型。BCG治疗组分别予模型建立后30 min、24 h、48 h大鼠腹腔注射BCG(105CFU),另外两组大鼠腹腔注射等剂量生理盐水。造模成功后应用BBB评分法对各组大鼠的后肢功能进行评分。14 d后处死大鼠,提取血清及脊髓组织标本,用HE染色观察病变组织浸润的中性粒细胞和巨噬细胞变化;用ELISA法检测脊髓匀浆促炎因子和抑炎因子变化。结果与假手术组相比,模型组大鼠后肢功能明显下降,而BCG治疗组较模型组有所改善;HE染色可见BCG治疗组炎症细胞较模型组减少、空洞较模型组减小。模型组中TNF-α、IL-1β及IL-6含量高于卡介苗治疗组(P<0.05),TGF-β和IL-10含量低于BCG治疗组(P<0.05)。结论BCG具有免疫调节及抗炎作用,进而抑制SCI后的免疫炎症反应,从而发挥脊髓保护作用。

Objective To investigate the effects of BCG vaccine on inflammatory factors after acute spinal cord injury in rats.Methods The total of 72 healthy adult SD male rats with a body weight of 250-300g were randomly divided into three groups which were sham operation group,model group and BCG treatment group,with 24 rats in each group according to random number table.The sham operation group was treated with laminectomy only,and the modified Allen's method was used as the model of spinal cord injury in the latter two groups.Rats in the BCG treatment group were intraperitoneally injected with BCG vaccine(105CFU)30 min,24 h and 48 h after the establishment of the model,respectively,and rats in the other two groups were intraperitoneally injected with equal dose of normal saline.After successful modeling,BBB scoring method was used to score the hind limb function of rats in each group.After 14 days,the rats were sacrificed,and serum and spinal cord tissue samples were extracted.HE staining was used to observe the changes of neutrophils and macrophages in the lesions.The changes of pro-inflammatory factor and anti-inflammatory factor in spinal cord homogenate were detected by ELISA.Results Compared with the control group,the hind limb function of rats in model group was significantly decreased,while that in BCG group was improved.HE staining showed that there were fewer inflammatory cells and cavities in the BCG treatment group than in the model group.Contents of TNF-α,IL-1βand IL-6 in model group were higher than those in BCG treatment group(P<0.05),while the contents of TGF-βand IL-10 in model group were lower than those in BCG treatment group(P<0.05).Conclusion BCG has immunoregulatory and anti-inflammatory effects,and can inhibit the immune inflammatory response after spinal cord injury,thus playing a protective role in spinal cord.