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脑缺血为高发的脑血管疾病,且常给病人带来不可逆性伤害.作为传统的抗炎药物,小檗碱(BBR)近年来显示出对脑缺血的防治作用,但是其作用机制尚未完全清楚.为此,我们从体内体外对其作用机制进行了研究.我们发现PPARγ是小檗碱的作用靶点之一:小檗碱在缺血再灌损伤中可以上调PPARγ表达.抑制PPARγ可以减弱小檗碱对缺血再灌损伤神经细胞的保护作用.此外,我们还发现脑缺血损伤过程中BBR可以降低DAN甲基化,下调甲基化转移酶DNMT1和DNMT3a的表达.同时可以降低PPARγ启动区甲基化水平.上述结果提示,PPARγ是BBR的主要作用靶点之一.在脑缺血再灌注损伤中,BBR促进PPARγ表达的作用机制与其抑制启动子区的甲基化水平有关.“,”Cerebral ischemia has higher incidence and causes irreversible damage to people.As a traditional drug for anti-inflammation,berberine (BBR) has recently been reported to have protective effect against cerebral ischemia.However,the mechanism has not been explored thoroughly.By employing in vivo and in vitro models for cerebral ischemia and reperfusion,we studied the mechanism of BBR against the ischemia-reperfusion.We found that BBR regulated the expression ofperoxisome proliferator-activated receptor (PPARγ) in a specific way upon ischemia-reperfusion injury.BBR enhanced the PPARγ expression during cerebral ischemia-reperfusion.By inhibiting PPARγ activity uisng GW9662,a PPARγ inhibitor,we confirmed that BBR protected the mouse brain against the ischemia in a PPARγ-dependent mechanism.In addition,we found that BBR reduced the overall global methylation,declined the expressions of DNMT 1 (DNA methyltransferases 1) and DNMT3a (DNA methyltransferases 3a) in the ischemia-reperfusion and reduced the methylation of PPARγ promoter region.Therefore,our data suggested that PPARγ was one of major targets of BBR,and such BBR-induced PPARγ expression during cerebral ischemia and reperfusion might be correlated to the reduced methylation of PPARγ promoter.