孕酮对蛛网膜下腔出血后早期脑损伤的保护作用

目的探讨孕酮(progesterone,PG)对大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期脑损伤(early brain injury,EBI)的保护作用及其机制。方法健康雄性SD大鼠48只按随机数字表法分为假手术组(Sham组)、蛛网膜下腔出血组(SAH组)和孕酮组(PG组)。采用枕大池自体血注入法建立蛛网膜下腔出血模型。各组于处理后48 h经苏木素-伊红染色观察海马神经元的组织形态学变化。应用原位末端标记法(TUNEL)检测海马神经元凋亡。运用免疫组织化学法检测大鼠海马中抗凋亡蛋白Bcl-2和促凋亡蛋白Bax的表达。结果与SAH组相比,PG组海马凋亡细胞数显著减少(P<0.05),Bcl-2表达升高(P<0.05),Bax表达下降(P<0.05)。结论孕酮可能通过促进Bcl-2的表达和降低Bax的表达(即提高Bcl-2/Bax比值),而抑制海马神经元的凋亡,对蛛网膜下腔出血后早期脑损伤发挥保护作用。

Protective effects of progesterone on early brain injury in rats after subarachnoid hemorrhage

Objective To investigate the effects of progesterone on early brain injury in rats after subarachnoid hemorrhage(SAH) and the possible mechanism involved.Methods Forty-eight adult male SD rats were randomly divided into three groups: the Sham operation group,the SAH group and the progesterone group(PG).An SAH model was established by injecting autologous blood into the cisterna magna.After 48 h,the morphology of hippocampal neural cells was examined in sections stained with hematoxylin and eosinfor all groups.Neuronal apoptosis in the hippocampus was assessed by TUNEL.Expression of Bcl-2(an anti-apoptotic protein) and Bax(a pro-apoptotic protein) was investigated with immunohistochemistry.Results Compared with the SAH group,the PG group exhibited significantly low rates of apoptosis in the hippocampus neurons(P<0.05),with expression of Bcl-2 up-regulated(P<0.05) and Bax down-regulated(P<0.05).Conclusion Progesterone apparently enhances Bcl-2 expression and inhibits Bax expression(thus increasing the Bcl-2/Bax ratio),leading to low apoptosis rates in hippocampus neuronal cells.This is likely responsible for the observed protective effects of progesterone on the EBI after SAH.