黄体酮对大鼠缺血再灌注脑组织细胞凋亡及Bcl-2、Bax表达的影响

Effect of progesterone on apoptosis and expression of Bcl-2 and Bax protein in rats during focal cerebral ischemia/reperfusion injury

目的探讨黄体酮对缺血再灌注脑损伤的保护机制。方法采用SD大鼠局灶性脑缺血再灌注模型(MCAO),将48只SD大鼠随机等分为6组假手术组、脑缺血再灌注组、溶剂(DMSO)对照组、黄体酮(PROG)预防组、PROG治疗组、PROG防治组,应用免疫组织化学和原位末端标记(ISEL)法检测脑组织细胞凋亡及凋亡相关蛋白Bcl-2、Bax的表达情况。结果假手术组每高倍视野下凋亡细胞数为1.88±0.25,缺血再灌注组为41.38±3.85,DMSO组为38.13±5.69,预防组为22.88±2.70,治疗组为25.63±2.93,防治组为20.88±2.30;缺血再灌注组每高倍视野下Bcl-2蛋白阳性细胞数为9.50±1.69,DMSO组为10.25±2.61,预防组为17.13±1.13,治疗组为16.63±1.30,防治组为23.50±1.93;缺血再灌注组每高倍视野下Bax蛋白阳性细胞数为28.13±2.75,DMSO组为27.75±3.06,预防组为14.25±1.83,治疗组为13.00±1.85,防治组为11.38±1.41。各PROG处理组(预防组、治疗组及防治组)3项指标与缺血再灌注组、DMSO组之间比较,差异均有统计学意义(P<0.05)。结论PROG可抑制脑神经细胞中Bax表达,上调Bcl-2表达,从而抑制脑细胞凋亡,发挥脑保护作用。

Aim： To study the neuroprotective effects and molecular mechanism of progesterone on ischemia/reperfusion injury. Methods：The rats with middle cerebral artery ocelusion （MACO） was described by Zea-Longa for 2 h and reperfusion for 24 h. A total of 48 male rats were divided randomly into sham operation group, ischmia/reperfusion （I/R） group, dimethl sulfoxide （DMSO） group,and PROG pretreatment group, PROG posttreatment group, PROG pre ＋ posttreament group. The neurological deficit was measured by Zea-Longa method,and the immunohistoehemical method and ISEL reaction were used to facilitate the quantities of Bcl-2 and Bax protein and apoptosis in the brain tissue. Results： There were 9.50±1.69 cells in Bcl-2 immunostaining in the I/R group, 10.25±2.61 ceils in DMSO group, 17.13±1.13 cells in the the pretreatment group, 16.63± 1.30 cells in the posttreatment group, 23.50 ±1.93 cells in the pre ＋ posttreament group. There were 28. 13 ± 2.75 ceils in Bax immunostaining in the I/R group, 27.75 ± 3.06 eells in DMSO group, 14.25±1.83 cells in the the pretreatment group, 13.00±1.85 cells in the posttreatment group, 11.38±1.41 cells in the pre ＋ posttreament group. The number of apoptosic ceils was 1.88± 0.25 in the sham-operation group, 41.38 ±3.85 in the I/R group, 38.13± 5.69 in the DMSO group, 22.88 ±2.70 in the the pretreatment group, 25.63±2.93 in the posttreatment group, 20.88±2.30 in the pre ＋ posttreament group. There were singnificant differences between pretreament, posttreament, pre ＋ posttreament and control groups（ I/R, DMSO ） （ P 〈 0.05 ）. Conclusion ： PROG may protect the ischemic brain during reperfusion injury. Reducing the expression of Bax protein and apoptosis and increasing the expression the Bcl-2 protein would be one of the molecular mechanism.