孕酮对小鼠认知能力及星形胶质细胞表达的影响

Effects of progesterone administration on cognitive function and astrocytes in mice

目的研究孕酮对成年雌性去卵巢小鼠认知能力的影响,及其与星形胶质细胞GFAP免疫阳性细胞表达是否存在关联性。方法 60只雌性昆明小鼠随机分为5组,除假手术对照组(SHAM组)外,其余各组小鼠行双侧卵巢切除术。术后对各组小鼠分别腹腔注射不同剂量孕酮或生理盐水。用Y-型电迷宫测试系统测定小鼠的认知功能变化,免疫组化法测定星形胶质细胞(astrocytes,AC)标志物胶质纤维酸性蛋白(GFAP)免疫阳性细胞的表达和变化。结果小鼠认知功能测定中,去卵巢对照组(OVX组)小鼠与SHAM组小鼠相比,在第2、3时段正确反应次数显著降低(P<0.05),高孕酮剂量组(HP组)小鼠与OVX组相比,在第3时段正确反应次数显著增高(P<0.05);GFAP表达测定中,OVX组与SHAM组小鼠相比,GFAP阳性细胞AOD和阳性细胞面积表达水平增加(P<0.05),孕酮中剂量组(MP组)和HP组与OVX组小鼠相比,GFAP阳性细胞AOD和阳性细胞面积表达水平降低(P<0.05)。结论雌、孕激素的缺乏会引起成年雌性小鼠认知障碍,孕酮的长期补充治疗可以改善小鼠认知能力,其作用机制与星形胶质细胞的变化相关。

Objective To investigate the effects of progesterone administration on cognitive impairment and astrocytes in ovariectomized mice.Methods Sixty female Kunming mice served as sham control or received bilateral ovariectomy followed by a 90-day regimen of different PROG（50 mg/kg,100 mg/kg,200mg/kg,respectively） or normal saline（10 mL/kg） beginning from 2 weeks after ovariectomy operation.PROG injections were given once per 5 days by intraperitoneal injection.Astrocytes were observed with immunohistochemistry for GFAP.The Y-type maze was used to test the cognitive function of mice.Results In measuring the cognitive function of the mice,compared with the sham group,the correct reaction times of the OVX group were significantly reduced at the 2nd and 3rd phase（P 0.05）.Compared with the OVX group,the correct reaction times of the HP group were distinctly increased at the 3rd phase（P 0.05）;In measuring the GFAP of the mice,compared with the sham group,there were obvious increase in the expression level of the AOD and positive cell area of the OVX group（P 0.05）,compared with the OVX group,there were decrease in the expression level of the AOD and positive cell area of the MP group and the HP group（P 0.05）.Conclusion Progesterone administration could suppress the activation of astrocytes at brain issues and also could improve the cognitive function of aging mice.