Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill(YGP), a 10-component tradi...Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill(YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated m RNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated m RNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.展开更多
目的通过研究重组人红细胞生成素(recombinant human erythropoietin,rhEPO)对局灶性脯缺血再灌注大鼠基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和BCL-2表达的影响,探讨EPO脑保护作用的可能机制。方法应用线栓法建立...目的通过研究重组人红细胞生成素(recombinant human erythropoietin,rhEPO)对局灶性脯缺血再灌注大鼠基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和BCL-2表达的影响,探讨EPO脑保护作用的可能机制。方法应用线栓法建立大鼠大脑中动脉闭塞再灌注(middle cerebral artery occlusion/reperfusion,MCAO/R)模型,腹腔注射rhEPO进行干预,通过HE染色光镜观察组织病理学变化,应用免疫组化技术检测缺血侧大脑皮质MMP-9和BCL-2的表达。结果HE染色:在各时间点,rhEPO组存活神经细胞数量显著较多,损伤程度显著较轻。MMP-9免疫组化染色:正常对照组和假手术组偶见阳性细胞;生理盐水对照组缺血侧脑组织MMP-9阳性细胞在再灌注后6h开始出现,24h达高峰,72h开始减少;rhEPO组MMP-9阳性细胞变化趋势与生理盐水对照组相似,但在同一时间点显著少于生理盐水对照组(t分别为12.0236、12.6350和12.7796,P均〈0.01)。BCL-2免疫组化染色:对照组和假手术组末见阳性细胞;牛理盐水对照组缺血侧脑组织BCL-2阳性细胞数在再灌注后6h达高峰,24h数量减少,72h进一步减少;rhEPO组BCL-2阳性细胞变化趋势与生理盐水对照组相似,但在同一时间点显著多于生理盐水对照组(t分别为5.7631、8.1101和5.7987,P均〈0.01)。结论rhEPO町能通过抑制MMP-9表达和上调BCL-2表达抑制缺血侧皮质神经细胞凋亡而发挥保护作用。展开更多
基金supported by the National Natural Science Foundation of China,No.30471576,and 30872277a grant from the Innovative Research Program in Universities of the Ministry of Education of China,No.IRT0760
文摘Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill(YGP), a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated m RNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated m RNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.