鞘内注射胶质细胞抑制剂对CCD大鼠脊髓星形胶质细胞的影响

Effect of Intrathecal Administration of Glia Cell Metabolic Inhibitor on Astrocytes in Spinal Dorsal Horn of CCD rats

[目的]研究鞘内注射氟代柠檬酸（fluorocitrate FC）和米诺四环素（minocychine MC）对背根节慢性压迫模型（the experi ment model for chronic compression of dorsal root ganglion,CCD）大鼠脊髓背角星形胶质细胞活化增殖的影响。[方法]采用大鼠脊髓背根节慢性压迫实验模型,96只鞘内置管SD大鼠分为第7天组（A组）和第14天组（B组）,每组随机分为六个亚组组,每小组（n=8）包括：假手术（sham）组,CCD组,溶剂磷酸盐缓冲生理盐水（PBS）组（0.01 mmol/L PBS 20μLi.t.）,FC组（1μmol/L FC20μLi.t.）,MC组（5 g/L MC 20μLi.t.）,MC＋FC组（1μmol/L FC和5 g/L MC混合液20μLi.t.）。术后每天给药一次,分别于术后d7和d14运用免疫荧光化学方法观察脊髓背角胶原纤维酸性蛋白（GFAP）的表达。[结果]脊髓背角GFAP阳性表达CCD、PBS、FC组在Ⅰ-Ⅳ层都表达明显,在数目上没有差异性;而MC、MC＋FC组主要集中在Ⅰ-Ⅱ层,Ⅲ、Ⅳ层在数目上有明显减少。CCD组和PBS组胞体比其余各组明显肥大。[结论]鞘内给药后,慢性神经痛大鼠脊髓背角星形胶质细胞GFAP表达减少,提示小胶质细胞抑制剂MC能很好的抑制星形胶质细胞的活化,小胶质细胞在星形胶质细胞活化的形成和维持中可能起重要作用。

[Objective]To study the effect of intrathecal injection（IT） of glia cell metabolic inhibitor fluorocitrate（FC） and minocychine（MC） on activation and proliferation of the astrocytes in spinal dorsal horn in chronic compression of dorsal root ganglia（CCD） rats.[Methods] A total of 96 SD rats with intrathecal catheter were divided into 7-day group（Group A） and 14-day group（Group B）.Each group was randomly divided into six groups（n=8） which included sham operation group,CCD group,PBS（solvent phosphate buffered saline） group（0.01mmol/L PBS 20μL i.t.）,FC group（1μmol/L FC 20μL i.t.）,MC group（5g/L MC 20μL i.t.） and MC＋FC group（the mixture of 1μmol/L FC and 5g/L MC 20μL i.t.）.On the 7th and 14th after operation,the animals were sacrificed and L4~5 segments of spinal cord were removed for detection of glia fibrillary acidic protein（GFAP） in the spinal dorsal horn by immunofluorescent techniques.[Results]The number of GFAP positive staining didn＇t change in the CCD,PBS and FC groups while there was significantly decreased in MC group and MC＋FC group in Ⅲ~Ⅳ laminae of spinal dorsal horn on the ipsilateral side under the microscopy.At the same time,cell body was more hypertrophic in the CCD group and PBS group than that in other groups.[Conclusion] After intrathecal administration,GFAP expression in the astrocytes in spinal dorsal horn of the affected side in neuralgia rats is decreased which suggests that microglia metabolic inhibitor minocychine can inhibit activation of astrocytes and the microglia cell may play an important role in the formation and maintenance of the activation of astrocytes.