P-糖蛋白
缺血
小胶质细胞
细胞凋亡
脑缺血
脑损伤
野生型
基因剔除小鼠
药理学
内分泌学
生物
内科学
免疫学
医学
炎症
基因
多重耐药
受体
生物化学
突变体
抗生素
作者
Michihiro Murozono,Takayuki Kobayashi,Shusuke Sekine,Takayasu Kakinuma
出处
期刊:Neuro endocrinology letters
日期:2020-12-01
卷期号:41 (5): 231-238
被引量:1
摘要
OBJECTIVES P-glycoprotein (P-gp), produced by the multidrug resistance (mdr1a) gene, is present in vascular endothelial cells, astrocytes, and microglia in the brain. We previously reported that P-gp aggravated cerebral infarct. Therefore, modulation of the function of P-gp is important for the treatment of brain ischemia. Here, we examined how P-gp exacerbates ischemic damage in the brain. METHODS Experiments were performed using mdr1a knockout (KO) mice and wild-type mice. Mice of both groups were subjected to transient focal ischemia and Bcl-2 family proteins, p-glycoprotein and cytokines were measured. RESULTS At 48 h after reperfusion, the expression of Bcl-2 protein in the brains of mdr1a KO mice was significantly greater compared with that of wild-type mice. The expression of brain Bax protein in mdr1a KO mice was significantly lower compared with that of wild-type mice. At 6 h after reperfusion, the expression of plasma IL-6 in mdr1a KO mice was significantly lower compared with that of wild-type mice. CONCLUSION These results indicate that P-gp derived from the mdr1a gene has pro-apoptotic functions mediated through Bcl family proteins and increased IL-6, which exacerbates ischemic damage in the brain. In summary, the inhibition of P-gp function is an effective strategy to protect against brain damage caused by ischemic damage.
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