ANA-12在大鼠坐骨神经慢性压迫性损伤中对星形胶质细胞活化和自噬的作用

Effects of ANA-12 on astrocyte activation and autophagy in chronic compression injury of rat sciatic nerve

目的探究ANA-12在大鼠坐骨神经慢性压迫性损伤(chronic constriction injury,CCI)中对星形胶质细胞胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)活化和LC3B自噬水平的作用,为ANA-12在坐骨神经慢性压迫性损伤中的应用提供新的见解。方法18只大鼠随机分为3组:假手术组、坐骨神经慢性压迫性损伤大鼠模型组(CCI组)和ANA-12组(坐骨神经慢性压迫性损伤大鼠+ANA-12干预组),每组6只。大鼠麻醉后,通过外科手术建立大鼠坐骨神经慢性压迫性损伤模型,并给予ANA-12腹腔注射持续处理14 d。于CCI诱导后第0、3、5、7、14天测定机械性反射阈值(MWT)和热收缩潜伏期(TWL)。动物处死后取脊髓组织做GFAP和LC3B免疫荧光表达检测。结果与假手术组相比,CCI大鼠的术后MWT和TWL值显著降低(P<0.05),脊髓组织星形胶质细胞活化和LC3B表达水平显著升高(P<0.05)。ANA-12治疗促进了CCI大鼠术后MWT和TWL值的恢复(P<0.05),抑制了脊髓组织星形胶质细胞活化但促进了LC3B的表达(P<0.05)。结论ANA-12治疗改善了大鼠坐骨神经慢性压迫性损伤的机械和热缩足痛阈值,可能与抑制星形胶质细胞活化和促进LC3B的自噬作用有关。

【Objective】To explore the effects of ANA-12 on glial fibrillary acidic protein(GFAP)activation of astrocytes and autophagy level of LC3B in chronic constriction injury(CCI)in rats,providing new clinical insights for the application of ANA-12 in CCI.【Methods】Eighteen rats were randomly divided into three groups(n=6,each):sham operation group,rat model with CCI group(CCI group),and ANA-12 group(rats with CCI+ANA-12 intervention group).After anesthesia,CCI rat model was established by surgery,and ANA-12 was injected into the abdomen for 14 days.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured on day 0,3,5,7,and 14 after CCI induction.GFAP and LC3B expression were detected by immunofluorescence in spinal cord tissues.【Results】Compared with the sham group,the values of MWT and TWL in CCI rats were significantly decreased(P<0.05),and the activation of astrocytes and LC3B expression levels in spinal cord tissue were increased(P<0.05).ANA-12 treatment promoted the recovery of MWT and TWL(P<0.05),inhibited the activation of astrocytes and promoted the expression of LC3B in spinal cord of CCI rats(P<0.05).【Conclusion】ANA-12 treatment improved the values of MWT and TWL in CCI rats,which may be related to the inhibition of astrocyte activation and the promotion of LC3B autophagy.