Loss of benefit from estrogen replacement therapy in diabetic ovariectomized female rats subjected to transient forebrain ischemia.
Loss of benefit from estrogen replacement therapy in diabetic ovariectomized female rats subjected to transient forebrain ischemia.
复制标题
患有短暂前脑缺血的糖尿病卵巢切除雌性大鼠失去雌激素替代疗法的益处。
DOI：
10.1016/s0006-8993(02)03484-4
复制
发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Pelligrino,DaleA
中科院分区：
文献类型：
--
作者：
Santizo,RobertoA;Xu,HaoLiang;Ye,Shuhua;Baughman,VernaL;Pelligrino,DaleA
在非糖尿病动物中，雌激素在局灶性和短暂性前脑缺血模型中显示出显著的神经保护作用。然而，这种神经保护作用在糖尿病患者中可能会减弱或丧失。在这项研究中，我们比较了完整的，卵巢切除（OVX）和17β-雌二醇（E2）治疗的OVX雌性大鼠的脑损伤水平，这些大鼠通过链脲佐菌素（STZ）导致糖尿病和慢性（约4周）高血糖。使大鼠经受20分钟的单侧短暂前脑缺血（皮质CBF减少至基线的20%）。每天分析神经功能，并在再灌注72小时时评价脑组织病理学（在H& E染色切片中）。从其他TUNEL染色切片中获得补充组织病理学信息。当比较三组的神经学结果评分时，E2处理的OVX雌性动物显示出最高程度的功能障碍，而完整雌性动物显示出最低程度的功能障碍（未用E2处理的OVX大鼠居中），完整组和E2处理组之间的差异具有统计学显著性。在H& E染色组织的区域组织病理学分析中经常观察到相同的顺序。与完整雌性动物相比，在海马CA 4区和皮质中观察到两个OVX组的神经元丢失幅度显著更高。此外，在背侧丘脑的E2处理组的细胞损失显着大于在完整的女性。这些结果通常通过TUNEL分析得到证实，67%的E2处理组、33%的对照OVX组和仅17%的完整雌性动物在多个区域显示TUNEL阳性细胞。总之，目前的研究结果强烈表明，雌激素替代疗法的神经保护作用可能会失去糖尿病雌性大鼠。
In nondiabetic animals, estrogen has been shown to provide significant neuroprotection in focal and transient forebrain ischemia models. However, that neuroprotection may be diminished or lost in the diabetic. In this study, we compared the level of brain damage in intact, ovariectomized (OVX) and 17β-estradiol (E2)-treated OVX female rats rendered diabetic and chronically (∼ 4 weeks) hyperglycemic via streptozotocin (STZ). Rats were subjected to 20 min of unilateral transient forebrain ischemia (reduction in cortical CBF to 20% of baseline). Neurologic function was analyzed daily and brain histopathology (in H&E-stained sections) was evaluated at 72 h of reperfusion. Supplemental histopathologic information was obtained from additional TUNEL-stained sections. When comparing neurologic outcome scores in the three groups, E2-treated OVX females displayed the highest degree of dysfunction and intact females the least (OVX rats not treated with E2were intermediate), with the difference between the intact and E2-treated groups being statistically significant. That same order was often observed with the regional histopathologic analyses of H&E-stained tissue. A significantly higher magnitude of neuronal loss in both OVX groups, when compared to intact females, was observed in the CA4 sector of the hippocampus and in the cortex. In addition, cell loss in the dorsal thalamus of the E2-treated group was significantly greater than in the intact females. Those results were generally corroborated by TUNEL-analysis, with 67% of the E2-treated, 33% of the control OVX, and only 17% of the intact females displaying TUNEL-positive cells in multiple regions. In conclusion, the present findings strongly suggest that the neuroprotective benefits of estrogen replacement therapy may be lost in the diabetic female rat.