Effect of ULK1 inhibitor SBI-0206965 on autophagy and function of placental trophoblasts in preeclampsia
Objective To observe the effect of SBI-0206965,a selective inhibitor of unc-51-like kinase(ULK)1,on auto-phagy and related functions of HTR-8/Svneo cells under hypoxia/reoxygenation.Methods A hypoxia/reoxygenation cul-ture model of trophoblast HTR-8/Svneo cells was established to simulate the pathophysiological state of oxidative stress in preeclampsia in vitro.The HTR-8/Svneo cells were divided into the normal control group,the hypoxia/reoxygenation group and the observation group(the hypoxic/reoxygenated cells treated with 10 μM SBI-0206965).The ROS activity was detec-ted by the glossy sperm method,the MDA levels were detected by the thiobarbituric acid method,the cell viability was de-tected by CCK-8 kit,the expression of Beclin1 and LC3B was detected by real-time quantitative PCR,cell migration was de-tected by scratching test,and cell invasion ability was detected by Transwell chamber assay.Results Compared with the control group,the ROS activity(t=8.418,P＜0.001),MDA content(t=5.788,P＜0.001),Beclin1 mRNA expression(t=8.987,P＜0.001)and LC3B mRNA expression(t=10.000,P＜0.001)were significantly increased,while cell viability(t=4.747,P＜0.001),cell invasion(t=5.923,P＜0.001)and cell migration(t=12.306,P＜0.001)were significantly de-creased in the hypoxia/reoxygenation group.Compared with the hypoxia/reoxygenation group,the ROS activity(t=2.641,P=0.019),MDA content(t=2.216,P=0.043),Beclinl mRNA expression(t=3.245,P=0.005)and LC3B mRNA ex-pression(t=3.194,P=0.006)were significantly decreased,while cell viability(t=2.234,P=0.041),cell invasion(t=2.847,P=0.012)and cell migration(t=4.549,P＜0.001)were significantly increased in the observation group.Conclu-sion ULK1 inhibitor SBI-0206965 can down-regulate the autophagy level of HTR-8/Svneo cells under oxidative stress in preeclampsia,and improve the activity and function of the damaged cells.
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