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

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(P0.05),7 d时则明显降低(P0.05)。同时,I/R组的IFN-β表达较假手术组在6 h时升高(P0.05),1 d和3 d时降低(P0.05),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(P0.05),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(P0.05)。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。

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

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 cerebral 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-β in 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-β in 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-β was 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-β in ischemic penumbra.