| 朱舜明,张荣怀,张学军,等.阿魏酸通过磷酸肌醇 3激酶 /丝氨酸 /苏氨酸蛋白激酶途径保护大鼠免受心肌缺血 /再灌注损伤[J].安徽医药,2022,26(11):2203-2208. |
| 阿魏酸通过磷酸肌醇 3激酶 /丝氨酸 /苏氨酸蛋白激酶途径保护大鼠免受心肌缺血 /再灌注损伤 |
| Ferulic acid protects rats from myocardial ischemia/reperfusion injury via the phosphoinositide 3-kinase/serine/threonine protein kinase pathway |
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| DOI：10.3969/j.issn.1009-6469.2022.11.019 |
| 中文关键词: 缺血再灌注 阿魏酸 PI3K/AKT信号通路 保护作用 |
| 英文关键词: Ischemia.reperfusion Ferulic acid PI3K/Akt signaling pathway Protective effect |
| 基金项目:陕西省自然科学基础研究计划( 2018JM7114) |
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| 中文摘要: |
| 目的研究阿魏酸对大鼠心肌缺血 /再灌注(I/R)损伤的保护作用及其可能的机制。方法将雄性 SD大鼠采用随机数字表法分为四组( n=12):假手术组( Sham组)， I/R模型组( I/R组)；阿魏酸 +I/R组( Fer+I/R组)；阿魏酸 +蛋白激酶抑制剂(LY294002)+I/R组( Fer+LY+I/R)。通过结扎左冠状动脉前降支 30 min，然后再灌注 2h，建立 I/R损伤大鼠模型。通过苏木精 -伊红( HE)染色分析大鼠的左心室病理学变化，结合透射电子显微镜观察其超微结构；通过 TUNEL/DAPI双重染色检测大鼠心肌细胞凋亡率。通过蛋白质印迹法( Western blotting)检测 PI3K/Akt信号通路关键调控因子的蛋白表达水平［包括 PI3K、p-Akt(Ser 473)、 Akt、eNOS、p-eNOS(Ser1177)和 p-mTOR(Ser2448)］以及血清超氧化物歧化酶( SOD)、丙二醛( MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素 6(IL-6)和 IL-1β水平。结果 HE染色，结果显示，相较于假手术组， I/R组大鼠心肌中表现出明显的炎性细胞浸润、细胞膜损伤、细胞坏死和水肿；而 Fer+I/R组大鼠表现心肌细胞坏死、炎性细胞浸润，细胞水肿均明显低于 I/R组，并且心肌纤维结构清晰完整。 TUNEL/DAPI双重染色结果显示， Fer+I/R组大鼠［(18.73±1.01)%］心肌细胞凋亡率明显低于 I/R组［(55.45±1.14)%］(P<0.001)。 Western blotting检测结果表明，与 I/R组相比， Fer+I/R组大鼠 Cleaved caspase-3蛋白表达水平显著降低( P<0.05)PI3K、p-Akt、Akt、p-eNOS(Ser1177)和 p-mTOR(Ser2448)蛋白表达明显上调( P<0.05)。相较于 I/R组，阿魏酸显著抑制 MDA5、T，NF-α、IL-6和 IL-1β的表达( P<0.05)并上调 SOD1蛋白表达水平( P<0.05)；而 LY294002处理逆转了阿魏酸在 I/R模型大鼠中对上述细胞因子的调控作用。结论阿，魏酸通过激活 PI3K/Akt信号通路抑制心肌细胞凋亡，减轻炎症反应和氧化应激水平，保护大鼠免受缺血 /再灌注诱导的心肌损伤。 |
| 英文摘要: |
| Objective To study the protective effect of ferulic acid on myocardial ischemia/reperfusion (I/R) injury in rats and its po. tential mechanism.Methods Male Sprague.Dawley (SD) rats were randomly divided into 4 groups (n=12): sham operation (sham)group, I/R group; ferulic acid+I/R (FER+I/R) group; and ferulic acid+LY294002 (protein kinase inhibitors)+I/R (FER+LY+I/R) group.A rat model of I/R injury was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for2 h. The pathological changes in the left ventricle of rats were analyzed by hematoxylin-eosin (HE) staining, and the ultrastructure wasobserved by transmission electron microscopy. The apoptosis rate of rat cardiomyocytes was detected by TUNEL/DAPI dual staining.Western blotting was used to detect the protein expression levels of key regulators of the PI3K/Akt signaling pathway, including PI3K,p-Akt (Ser473), Akt, eNOS, p-eNOS (Ser1177) and p-mTOR (Ser2448), and serum levels of superoxide dismutase (SOD), malondialde. hyde (MDA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and IL-1β.Results The results of HE staining showed that com. pared with the sham-operation group, the rats in the I/R group showed obvious inflammatory cell infiltration, cell membrane damage,cell necrosis and edema in the myocardium, while the rats in the Fer+I/R group showed myocardial cell necrosis, inflammatory cell in.filtration and cell edema that were significantly lower than those in the I/R group, and the myocardial fiber structure was clear and com.plete. The results of TUNEL/DAPI dual staining showed that the apoptosis rate of cardiomyocytes in the Fer+I/R group was (18.73±1.01)%, which was significantly lower than that in the I/R group (55.45±1.14)% (P < 0.001). Western blotting results showed that com. pared with the I/R group, the expression level of cleaved caspase-3 protein in the Fer+I/R group was significantly decreased (P < 0.05), PI3K, p-Akt, Akt, p-eNOS (Ser1177) and p-mTOR (Ser2448) protein expression was significantly upregulated (P < 0.05). Compared with the I/R group, ferulic acid significantly inhibited the expression of MDA, TNF-α, IL-6 and IL-1β (P<0.05) and upregulated the ex. pression level of SOD protein (P < 0.05). LY294002 treatment reversed the regulatory effect of ferulic acid on the aforementioned cyto. kines in I/R model rats.Conclusion Ferulic acid inhibited cardiomyocyte apoptosis by activating the PI3K/Akt signaling pathway, at.tenuated the level of the inflammatory response and oxidative stress, and protected rats from I/R-induced myocardial injury. |
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