丙泊酚通过激活SIRT1/Nrf2信号抑制铁死亡保护大鼠脑缺血/再灌注损伤的作用及机制研究

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Abstract Objective To explore the mechanism of propofol in regulating ferroptosis through SIRT1/Nrf2 pathway in rats with cerebral ischemia/reperfusion (I/R) injury. Methods The rat brain I/R model was constructed and the mouse hippocampal neuron HT22 cells were treated with oxygen and glucose deprivation/reoxygenation (OGD/R) in vitro and pre-treated with propofol. Cerebral infarct volume was analyzed by TTC staining. Western blot was carried out to determine related protein levels of SIRT1/Nrf2 signaling and ferroptosis in the brain tissue of rats. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and Fe²⁺ levels in the brain tissue of rats were detected by corresponding kits. SIRT1 was silenced in rats and HT22 cells, and SIRT1 and Nrf2 were silenced simultaneously in HT22 cells. The changes of SIRT1/Nrf2 signaling related proteins and ferroptosis in rat brain tissue were detected. HT22 cells were treated with autophagy inhibitor 3-MA, and the expression of autophagy-related proteins and ferroptosis changes were detected. Results The cerebral infarct volume of the I/R group was higher than those of the Sham group, and the propofol group were lower than those of the I/R group. The protein expressions of SIRT1, Nrf2, HO-1 and NQO1 in brain tissue of rats in I/R group were higher than those in Sham group, and those in propofol group were lower than I/R group. Compared with Sham group, ROS, MDA, Fe²⁺ and Ptgs2 levels in the brain tissue of rats in I/R group were increased, and SOD and GPX-4 levels were decreased, and propofol reversed these results (P<0.01). Compared with the propofol group, SIRT1 silencing increased ROS, MDA and Fe²⁺ levels and decreased SOD level in the brain tissue of I/R rats and HT22 cells after ODG/R, and overexpression of Nrf2 reversed these results. After ODG/R, the ratio of LC3Ⅱ/Ⅰ were increased in HT22 cells, and propofol down-regulated these results. The silence of SIRT1 up-regulated the ratio of LC3Ⅱ/Ⅰ, and the autophagy inhibitor treatment down-regulated these results, reduced the levels of ROS, MDA and Fe²⁺, and increased the level of SOD. Conclusion Propofol inhibits autophagy and reduces ferroptosis through activation of SIRT1/Nrf2 pathway to protect brain I/R injury in rats.

Key words： propofol SIRT1/Nrf2 cerebral ischemia/reperfusion (I/R) injury autophagy ferroptosis

Received: 18 January 2023

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R363

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	XU Jiajia
	YE Liangliang
	HU Jian
	ZHOU Litian

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XU Jiajia,YE Liangliang,HU Jian等. Propofol alleviates cerebral ischemia/reperfusion injury in rats by activating SIRT1/Nrf2 signaling to inhibit ferroptosis[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(2): 22-29.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2023/V20/I2/22

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