丙戊酸对大鼠脊髓损伤后中央管周围星形胶质细胞增生的影响

Effect of valproic acid on astrocyte proliferation around the central canal in rats following spinal cord injury

目的探讨丙戊酸对大鼠脊髓损伤后中央管周围星形胶质细胞增生的作用及机制。方法45只Wister成年大鼠按随机数字表法分为正常对照组（5只）、损伤组（20只）和治疗组（20只）。损伤组和治疗组采用Allen打击模型（打击强度为10g×15mm），制备T10节段急性脊髓损伤，治疗组在损伤后30min给予丙戊酸治疗，按300mg·kg-1·d-1经腹腔分2次注射，直至各损伤时相点；损伤组以相同方法注射相同剂量等渗盐水。于损伤后1，3，7，14d各时相点进行后肢功能BBB评分；观察损伤脊髓中央管周围星形胶质细胞的增殖及胶质纤维酸性蛋白（glialfi-brousacidprotein，GFAP）表达的动态变化。结果正常对照组脊髓中央管周围星形胶质细胞数量较少，GFAP的表达也较低。而损伤组星形胶质细胞于伤后24h在中央管周围开始出现少量增加，GFAP荧光强度为24．6±3．6，3d时荧光强度达高峰为69．2±6．4，一直持续到7d的（56．7±5．6），14d为35．4±4．3，有所降低，但仍然高于正常对照组的（11．2±1．6）。而治疗组在伤后3，7d时脊髓中央管周围星型胶质细胞的增生低于损伤组，GFAP的表达分别为47．8±5．3，42．2±6．7，均低于损伤组（F=177．6，P〈0．05）。BBB评分在伤后3，7，14d损伤组分别为4．60±0．54，6．65±0．67，9．40±1．14，治疗组分别为7．80±0．83，12．00±1．58，16．60±1．12（F=1133．6，P〈0．05）。结论丙戊酸可通过抑制GFAP的表达减少脊髓损伤后中央管附近胶质细胞的增生，并对损伤脊髓的功能具有一定的修复作用。

Objective To investigate the effect and mechanism of valproic acid in preventing as- trocyte proliferation around the central canal of rats following spinal cord injury. Methods Forty-five Wister rats were divided into normal control group （ n = 5 ）, injury group （ n = 20 ） and treatment group （n = 20） according to random number table. Animal models of acute spinal cord injury were produced at T10 using Allen＇ s method by dropping a 10 g weight from a 15 mm height. Rats in treatment group received intraperitoneal injection of valproic acid （300 mg . kg-1 . d-1 in two divided doses） at 30 minutes postin- jury. Instead, rats in injury group were injected with an equal volume of saline in the same way. Hindlimb function was evaluated using BBB scoring system at 1, 3, 7, and 14 days postinjury. Astrocytes prolifera- tion around central canal and expression of glial fibrous acid protein （GFAP） were examined. Results In normal control group, few astrocytes around spinal central canal and a low expression of GFAP were de- tected. In injury group, astrocytes began to increase at 24 hours postinjury; fluorescence intensity for GFAP was 24.6 ± 3.6 at 24 hours, reached a peak of 69.2 ±6.4 at 3 days, maintained a high level of 56.7 ± 5.6 at 7 days, and reduced to 35.4 ± 4.3 at 14 days, a level that remained higher than that in normal control group （ 11.2 ±1.6）. Whereas in treatment group at 3 and 7 days, astrocyte proliferation around spinal central canal was lower than that in injury group; GFAP expressions （47.8± 5.3 and 42.2 ±6.7） were lower than those in injury group （ F = 177.6, P 〈 0.05 ）. At 3, 7, and 14 days, BBB scores in treatment group （7.80 ±0. 83, 12.00± 1.58, and 16.60 ± 1.12 respectively） were significantlyhigher than those in injury group （4.60 ± 0.54, 6.65 ± 0. 67, and 9.40 ±1.14 respectively） （ F = 1 113.6, P 〈 0.05）. Conclusion After spinal cord injury, valproic acid reduces astrocyte proliferation around central canal via inhibiting GFAP expression to promote functional recovery.