丹酚酸A对大鼠脑缺血再灌注后细胞凋亡的保护作用及其机制

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摘要目的：探讨丹酚酸A（Sal A）对大鼠脑缺血再灌注后细胞凋亡的保护作用及其机制。方法：采用线拴法构建大脑中动脉缺血再灌注（MCA-IR）模型。将正常SD大鼠随机分为假手术组（对照组）、MCA-IR模型组（MCA-IR组)、Sal A+MCA-IR组（Sal A组）；Sal A组于建模前1周每日腹腔注射1.0、2.5、5.0 mg/kg Sal A。于再灌注后24 h取梗死脑组织用TUNEL法检测脑细胞凋亡，Western blot检测磷酸化Akt（p-Akt）和Akt的表达，免疫组织化学法检测海马区胞浆型磷脂酶A2（cPLA2）的表达。结果：Sal A组海马CA1区细胞凋亡率和MDA含量较MCA-IR组降低，而SOD量较MCA-IR组显著增加（P＜0.05），MCA-IR组海马区p-Akt表达较对照组显著下降（P＜0.05），而cPLA2较对照组显著增高（P＜0.05），1.0、2.5、5.0 mg/kg Sal A预处理后， MCA-IR模型大鼠海马区cPLA2表达显著降低（P＜0.05），而p-Akt表达显著增加（P＜0.05）。结论：Sal A降低缺血再灌注损伤后细胞凋亡，起到损伤保护作用，其机制与其降低cPLA2表达，激活Akt信号通路有关。

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关键词 ：丹酚酸A, 细胞凋亡, 蛋白激酶B, 脑缺血再灌注, 大鼠

Abstract：Objective: To investigate the protective effect of salvianolic acid A (Sal A) against apoptosis in cerebral ischemia-reperfusion model and its mechanism. Methods: SD rats were randomly divided into sham operation group (sham group), middle cerebral artery ischemia reperfusion model (MCA-IR) group (MCA-IR group), Sal A pretreatment and MCA-IR group (Sal A+MCA-IR group). MCA-IR was established in MCA-IR group and Sal A+MCA-IR group in which rats were pre-treated with 1.0, 2.5, 5.0 mg/kg Sal A via intraperitoneal injection daily for 1 week. The artery were reperfused for 24 h and rats were sacrificed. TUNEL was used to assayed the cell apoptosis, immunohistochemistry was implied to test the expression of cPLA2 and Western blot was undergone to analyzed p-Akt and total Akt. Immunohistochemistry was used to analyze the expression of cPLA2. Results: The apoptosis rate and MDA level in Sal A+MCA-IR group was lower, but SOD was higher than that in MCA-IR group (P<0.05). The expression of p-Akt in Hippocampus of MCA-IR model decreased, while the expression of cPLA2 increased significantly compared with control group. 1.0, 2.5, 5.0 mg/kg Sal A pretreatment reversed the decrease of p-Akt and increase of cPLA2. Conclusion: Sal A inhibits the apoptosis through decreasing the expression of cPLA2 and activating Akt pathway signaling in MCA-IR model.

Key words： salvianolic acid A apoptosis protein kinase B ischemia-reperfusion rats

收稿日期: 2017-01-15

基金资助:浙江省医药卫生科技计划项目（2017KY170）；丽水市公益性技术应用项目（2016GYX39、2016GYX25）。

通讯作者: 邱伟文，主任医师，Email：weiwenq@hotmail.com

作者简介: 彭潇（1983-），男，浙江丽水人，主治医师。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I9/674

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