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首页> 外文期刊>Drug Design, Development and Therapy >Andrographolide attenuates bupivacaine-induced cytotoxicity in SH-SY5Y cells through preserving Akt/mTOR activity
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Andrographolide attenuates bupivacaine-induced cytotoxicity in SH-SY5Y cells through preserving Akt/mTOR activity

机译:穿心莲内酯通过保留Akt / mTOR活性减弱布比卡因诱导的SH-SY5Y细胞的细胞毒性

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Background: Bupivacaine (Bup) is the most commonly used local anesthetic. However, Bup induces cytotoxicity, especially in older patients. Recent reports have indicated that andrographolide (Andro) exhibits protective effects on human neurons. Nevertheless, whether Andro can inhibit Bup-induced cytotoxicity remains unclear. As such, we investigated the effect of Andro on Bup-induced cytotoxicity of SH-SY5Y cells in the present study. Methods: Western blotting was used to examine expression of Bax, Bcl2, active caspase 3, p-Akt, and p-mTOR in SH-SY5Y cells. In addition, ELISA was used to detect levels of total glutathione and reactive oxygen species in cells. Results: We found that Andro attenuated Bup-induced cytotoxicity of SH-SY5Y cells. In addition, Andro inhibited Bup-induced apoptosis via downregulating the expression of Bax and active caspase 3 and upregulating the proteins Bcl2, p-Akt, and p-mTOR in SH-SY5Y cells. Moreover, Andro alleviated Bup-induced oxidative damage in SH-SY5Y cells via downregulating the level of reactive oxygen species and upregulating of the level of total glutathione. More significantly, inhibition of Akt abolished the protective effect of Andro in Bup-treated SH-SY5Y cells. Conclusion: Our findings indicated that Andro played a neuroprotective role via preserving Akt/mTOR activity and increasing antioxidative status in Bup-treated SH-SY5Y cells. Therefore, Andro may be a potential agent for the treatment of human cytotoxicity induced by Bup.
机译:背景:布比卡因(Bup)是最常用的局部麻醉剂。但是,Bup会引起细胞毒性,尤其是在老年患者中。最近的报道表明穿心莲内酯(Andro)对人类神经元具有保护作用。然而,尚不清楚Andro是否可以抑制Bup诱导的细胞毒性。因此,在本研究中,我们研究了安德罗对Bup诱导的SH-SY5Y细胞的细胞毒性的作用。方法:采用蛋白质印迹法检测SH-SY5Y细胞中Bax,Bcl2,活性胱天蛋白酶3,p-Akt和p-mTOR的表达。此外,ELISA用于检测细胞中总谷胱甘肽和活性氧的水平。结果:我们发现安德罗减弱了Bup诱导的SH-SY5Y细胞的细胞毒性。此外,Andro通过下调Bax和活性胱天蛋白酶3的表达并上调SH-SY5Y细胞中的Bcl2,p-Akt和p-mTOR蛋白来抑制Bup诱导的凋亡。此外,Andro通过下调活性氧的含量和上调总谷胱甘肽的含量来减轻Bup诱导的SH-SY5Y细胞的氧化损伤。更重要的是,抑制Akt消除了Andro对Bup处理的SH-SY5Y细胞的保护作用。结论:我们的发现表明,安德罗在Bup处理的SH-SY5Y细胞中通过保留Akt / mTOR活性和增加抗氧化状态发挥神经保护作用。因此,Andro可能是治疗Bup诱导的人类细胞毒性的潜在药物。

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