羟基红花黄色素A与芍药苷联用对脑缺血再灌注大鼠脑组织p-Akt蛋白的影响

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目的 探讨羟基红花黄色素A(HSYA)与芍药苷(PF)联用对脑缺血再灌注大鼠脑组织磷酸化蛋白激酶B(p-Akt)的影响。方法 将160只SD大鼠随机分成HSYA组(5 mg·kg~(-1))、PF组(5 mg·kg~(-1))、预防治疗组(HSYA+PF,各5 mg·kg~(-1))、治疗组(HSYA+PF,各5 mg·kg~(-1))、银杏内酯组(5 mg·kg~(-1))、模型组、假手术治疗组(HSYA+PF,各5 mg·kg~(-1))、假手术空白组。采用右侧大脑中动脉线栓法(MACO)复制急性局灶性脑缺血再灌注模型,预防治疗组从造模前3天开始通过尾静脉注射给药,余各组造模后连续给药7天。再灌注6h后及取材前进行神经行为评分;氯化三苯基四氮唑染色观察并测定脑梗死面积比;HE染色观察各组大鼠海马区病理组织学变化;免疫组化法检测脑组织皮层区p-Akt蛋白表达情况。结果与假手术组比,其余各组首次神经功能缺失评分均显著增加(P<0.05);与模型组比较,预防治疗组首次神经功能缺失评分显著降低(P<0.05),各给药组用药后神经功能缺失评分显著降低(P<0.05)。与假手术空白组比较,模型组梗死面积百分比显著增加(P<0.05);与模型组比较,各给药组梗死面积百分比显著减少(P<0.05)。与模型组比较,预防治疗组、治疗组、银杏内酯组的脑组织皮层内p-Akt阳性细胞表达率显著升高(P<0.05),而HSYA组、PF组与模型组的差异无统计学意义(P>0.05);与治疗组比较,预防治疗组的p-Akt阳性细胞表达明显增加(P<0.05)。结论 HSYA与PF联用较单用对脑缺血再灌注损伤有更强的保护作用,这可能与其上调PI3K/AKT通路中p-Akt蛋白的表达量有关,且预防用药的保护作用更强。 Objective To investigate the effect of hydroxysafflor yellow A (HSYA) combined with paeoniflorin (PF) on phosphorylation of protein kinase B (p-Akt) in rat brain after cerebral ischemia-reperfusion. Methods 160 SD rats were randomly divided into HSYA group (5 mg · kg -1), PF group (5 mg · kg -1), prophylaxis group (HSYA + PF, 5 mg · kg -1 (5 mg · kg ~ (-1)), ginkgolide group (5 mg · kg ~ (-1)), untreated group and sham operation group HSYA + PF, each 5 mg · kg -1), sham operation group. The model of acute focal cerebral ischemia-reperfusion was reproduced by the right middle cerebral artery occlusion (MACO). The prophylaxis and treatment groups were given intravenous injection from the tail vein 3 days before modeling, 7 days. The neurobehavioral score was measured 6 h after reperfusion and before the material was taken. The area ratio of cerebral infarction was observed and measured by triphenyltetrazolium chloride staining. The histopathological changes of hippocampus in each group were observed by HE staining. Cortical p-Akt protein expression. Results Compared with the sham-operation group, the scores of the first neurological deficit in the other groups were significantly increased (P <0.05). Compared with the model group, the first neurological deficit score of the prophylaxis group was significantly lower (P <0.05) Post-neurological deficit score was significantly lower (P <0.05). Compared with the sham operation group, the percentage of infarct area in the model group increased significantly (P <0.05). Compared with the model group, the percentage of infarction area in each group decreased significantly (P <0.05). Compared with the model group, the expression of p-Akt positive cells in the precancerous, therapeutic and ginkgolide groups was significantly increased (P <0.05), but there was no statistical difference between the HSYA group, the PF group and the model group (P> 0.05). Compared with the treatment group, the expression of p-Akt positive cells in the preventive treatment group was significantly increased (P <0.05). Conclusions HSYA combined with PF can protect cerebral ischemia-reperfusion injury more effectively than single-use, which may be related to its up-regulation of p-Akt protein expression in PI3K / AKT pathway and its preventive effect is stronger.
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