羟基红花黄素A对脑缺血再灌注后缺血半暗带自噬活性的调节作用

Modulation of autophagy in ischemic penumbra by hydroxysafflor yellow A after cerebral ischemia/reperfusion injury

目的:探讨脑缺血再灌注后羟基红花黄素A(hydroxysafflor yellow A,HYSA)对缺血半暗带自噬活性的调控机制。方法:构建雄性SD大鼠脑缺血90 min再灌注模型,分为假手术组、脑缺血再灌注(cerebral ischmia/reperfusion,I/R)组、I/R+HSYA组和假手术+HSYA组,分别在再灌注后6 h、1 d、3 d和7 d对大鼠进行改良神经功能缺损评分(modified neurological severity score,m NSS),同时检测缺血半暗带的自噬活性、凋亡及干扰素β(IFN-β)表达。结果:与假手术组比较,I/R组缺血半暗带在6 h^7 d内可见LC3-Ⅱ蛋白表达增高及SQSTM1/P62蛋白降解,提示自噬激活;与I/R组比较,I/R+HSYA组的自噬活性在1 d和3 d时明显升高(P<0.05),7 d时则明显降低(P<0.05)。同时,I/R组的IFN-β表达较假手术组在6 h时升高(P<0.05),1 d和3 d时降低(P<0.05),7 d时恢复正常;而I/R+HSYA组的IFN-β表达在1 d和3 d时明显高于假手术组和I/R组(P<0.05),并且3 d时的细胞凋亡少于I/R组,m NSS评分自4 d起明显低于I/R组(P<0.05)。结论:HSYA可动态调节缺血半暗带的自噬活性和IFN-β表达,从而改善脑缺血再灌注损伤。

AIM： To clarify the modulation of autophagy in ischemic penumbra by hydroxysafflor yellow A （ HSYA） after cerebral ischemia/reperfusion （ I/R） injury.METHODS：Male SD rats subjected to transient middle cere-bral artery occlusion for 90 min were randomly divided into 4 groups：sham-operation （sham） group, cerebral I/R （I/R） group, I/R＋HSYA group and sham＋HSYA group.Modified neurological severity score （mNSS） was used to evaluate the neurological deficits of the rats at 6 h, 1 d, 3 d and 7 d after reperfusion , accompanied by the detection of autophagy , apoptosis and mRNA expression of IFN-βin ischemic penumbra .RESULTS：Compared with sham group , upregulation of LC3-Ⅱand degradation of SQSTM1/P62 were observed in I/R group, indicating the activation of autophagy after I/R.The activation of autophagy in I/R＋HSYA group was significantly enhanced by HSYA on day 1 and day 3, and inhibited on day 7, as compared with I/R group （P〈0.05）.Besides, the mRNA expression of IFN-βin I/R group was significantly upregulated at 6 h, then downregulated on day 1 and day 3, and returned to basal level on day 7, as compared with sham group （P〈0.05）.In I/R＋HSYA group, the mRNA expression of IFN-βwas significantly upregulated on day 1 and day 3, accompanied by the inhibition of apoptosis on day 3 and the significantly decreased mNSS from day 4, as compared with I/R group （P〈0.05）.CONCLUSION：HSYA alleviates cerebral I/R injury by dynamically modulating the activation of autophagy and the expression of IFN-βin ischemic penumbra .