川芎嗪通过调节 PI3K/Akt/GSK-3β 信号通路发挥抗急性心肌缺血损伤的保护作用。
Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway.
机构信息
1Blood Transfusion Department, First Hospital of Jilin University, Changchun, Jilin China.
2Preclinical School of North Sichuan Medical College, Nanchong, Sichuan China.
出版信息
Cell Mol Biol Lett. 2019 Feb 26;24:17. doi: 10.1186/s11658-019-0141-5. eCollection 2019.
OBJECTIVE
We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO).
MATERIALS AND METHODS
Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg) and ISO + TMP (20 mg/kg). The rats in the three ISO + groups were pretreated with propranolol or TMP, while the rats in the control and ISO groups were pretreated with an equal volume of saline. Afterwards, the rats in the four administration groups were subcutaneously injected with ISO for two consecutive days. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the serum were measured using ELISA. The expressions of B-cell lymphoma-associated X-2 (Bax-2), B-cell lymphoma-2 (Bcl-2), phosphoinositide-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK-3β), MDA5 and SOD1 were determined using western blotting assay. The phosphorylation of PI3K, Akt and GSK-3β were also determined using western blotting assay. The left ventricles of the rats were extracted and stained using hematoxylin and eosin (H&E). The ST segment was recorded using electrocardiograms (ECGs).
RESULTS
Administration of TMP (10, 20 mg/kg) reduced the levels of MDA and CK and the activities of SOD and LDH in the serum. Pretreatment with TMP significantly reduced the levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Treatment with TMP also improved the histopathological alteration and decreased the ST elevation. Furthermore, TMP ameliorated the expressions of Cu, SOD1, MDA5, Bax-2, Bcl-2, p-PI3K, p-Akt and p-GSK-3β in ISO-induced rats.
CONCLUSIONS
Tetramethylpyrazine protected against injury due to AMI by regulating the PI3K/Akt /GSK-3β signaling pathway.
目的
研究川芎嗪（TMP）对异丙肾上腺素（ISO）诱导的急性心肌缺血（AMI）相关损伤的保护作用。
材料和方法
大鼠随机分为五组：对照组、ISO 组、ISO+心得安（10mg/kg）组、ISO+TMP（10mg/kg）组和 ISO+TMP（20mg/kg）组。ISO+三组大鼠预先给予心得安或 TMP 预处理，而对照组和 ISO 组大鼠给予等量生理盐水预处理。随后，四个给药组大鼠连续两天皮下注射 ISO。采用酶联免疫吸附法（ELISA）测定血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）水平。采用 Western blot 法测定 B 细胞淋巴瘤相关 X-2（Bax-2）、B 细胞淋巴瘤-2（Bcl-2）、磷酸肌醇 3-激酶（PI3K）、蛋白激酶 B（Akt）、糖原合酶激酶 3β（GSK-3β）、MDA5 和 SOD1 的表达。采用 Western blot 法测定 PI3K、Akt 和 GSK-3β的磷酸化。提取大鼠左心室，用苏木精和伊红（H&E）染色。采用心电图（ECG）记录 ST 段。
结果
TMP（10、20mg/kg）给药降低了血清 MDA 和 CK 水平及 SOD 和 LDH 活性。TMP 预处理显著降低了促炎细胞因子（包括 IL-1β、IL-6 和 TNF-α）的水平。TMP 治疗还改善了组织病理学改变并降低了 ST 抬高。此外，TMP 改善了 ISO 诱导的大鼠中 Cu、SOD1、MDA5、Bax-2、Bcl-2、p-PI3K、p-Akt 和 p-GSK-3β 的表达。
结论
川芎嗪通过调节 PI3K/Akt/GSK-3β信号通路，对 AMI 损伤起到保护作用。
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