黄体酮对颅脑损伤大鼠脑组织中Nogo-A、胶质纤维酸性蛋白及胰岛素样生长因子-1表达影响的研究

Effect of progesterone on expression of Nogo-A,GFAP and IGF-1 in rats after traumatic brain injury

目的研究颅脑损伤及黄体酮干预对大鼠脑组织内Nogo-A、胶质纤维酸性蛋白(GFAP)及胰岛素样生长因子-1(IGF-1)表达的影响,探讨黄体酮对颅脑损伤的神经保护作用及相关机制。方法健康雄性SD大鼠75只,随机分为假手术组、模型组和黄体酮治疗组,每组25只,并依据检测时间点进一步随机分为1、3、7、14、28d共5个亚组。假手术组大鼠仅切开顶部头皮去除颅骨,模型组和黄体酮治疗组建立大鼠中度脑挫裂伤模型。黄体酮治疗组于建模成功6h后开始予黄体酮(10mg/kg)腹腔注射,1次/d,直至动物处死。假手术组与模型组用等量0.9%氯化钠注射液腹腔注射,1次/d,直至动物处死。通过免疫组化检测各时间点大鼠病灶周围组织Nogo-A、GFAP及IGF-1表达水平。结果免疫组化结果显示,假手术组中Nogo-A、GFAP和IGF-1在各时间点均有表达,变化幅度较小。模型组各时间点脑组织Nogo-A、GFAP和IGF-1表达阳性细胞数均高于假手术组(均P<0 05),GFAP在3d达峰值,Nogo-A和IGF-1在7d达峰值,随后逐渐下降,28d接近原有水平。黄体酮治疗组GFAP表达阳性细胞数在3d达峰值,Nogo-A和IGF-1在7d达峰值;Nogo-A和GFAP在各个时间点的表达阳性细胞数均低于假手术组和模型组(均P<0.05),而IGF-1峰值较假手术组和模型组更高,随后呈下降趋势,14d时IGF-1表达阳性细胞数仍略高于模型组,直到28d才与假手术组无统计学差异。结论黄体酮能抑制颅脑损伤大鼠脑组织中Nogo-A、GFAP表达,上调IGF-1表达,具有减轻轴突生长抑制和抑制胶质瘢痕屏障形成的作用,并能促进相关神经营养因子表达,能改善颅脑损伤患者的预后。

Objective To investigate the effect of progesterone on the expression of Nogo-A, GFAP and IGF-1 in rats after traumatic brain injury. Methods Seventy five adult male SD rats were randomly divided into three groups with 25 in each group. Moderate cerebral contusion was induced by Feeney method in model and treatment groups, rats in sham group under- went craniectomy. Rats in treatment group received intraperitoneal injection of progesterone （10mg/kg. d） 6h after the induction of brain injury, same volume of normal saline was given for rats in model and sham groups. Five rats in each group were sacrificed in batches at ld, 3d, 7d, 14d and 28d after model induction or craniectomy. The expression of Nogo-A, GFAP and IGF-1 was detected by immunohistochemistry at all time points. Results The expression of Nogo-A, GFAP and IGF-1 in model group was higher than that in sham group at all time points; the expression of GFAP reached peak on 3d, the expression of Nogo-A and IGF-1 reached peak on 7d, then decreased gradually. The expression in treatment group presented the similar trends as model group; however, the expression of Nogo-A and GFAP as lower than the sham group and the mode[ group, the peak expression of IGF-I was higher than that in sham group and the model group, which was decreased gradually. Conclusion Progesterone can inhibit the expression of Nogo-A and GFAP and enhance the expression of IGF-1, which is associated with improvement of the prognosis of traumatic brain injury.