Résumé
Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.
Résumé
Objective To explore effect of cannabinoid receptor type 2(CB2R)on the expression of autophagy-related proteins LC3 and Beclin-1 in the hippocampal CA1 region of rats with status epilepticus ( SE). Methods SE model was established by treating lithium chloride-pilocarpine intraperitoneally injection in Sprague-Dawley(SD) rats. All the rats were randomly divided into four groups including Control group, Epilepsy group,Epilepsy + JWH-133 group and Epilepsy + AM630 group. JWH-133, AM630, and DMSO were injected 60 min before pilocarpine injection by intracerebroventricular injection ( Control group and Epilepsy group with DMSO,Epilepsy+JWH-133 group with JWH-133 and Epilepsy+AM630 group with AM630). At 24 h after SE,the epileptic symptoms were observed. HE staining was performed to observe the number changes of neurons in the hippocampal CA1 region. The spatiotemporal expressions of LC3 and Beclin-1 in the hippocampal CA1 region were observed using Double-label immunofluorescence and Western blot. Results Epileptic symptoms showed that rats in the control group had no obvious epileptic seizures. Those in Epilepsy group presented seizures about (13. 50 ± 0. 61)min after treated with pilocarpine and racine scale was (4. 33 ± 0. 47) scores. The latency period in Epilepsy+JWH-133 group was(19. 33 ± 0. 42) min and longer than that in the Epilepsy group(P<0. 05);Racine scale in Epilepsy+JWH-133 group was 3. 33 ± 0. 59 and less than the Epilepsy group( P<0. 05). The opposite effect was observed in Epilepsy+AM630 group. HE staining showed that compared with the Epilepsy group,the number of the hippocampal CA1 neu-rons increased in Epilepsy+JWH-133 group and decreased in Epilepsy+AM630 group. Immunofluorescence and Western blot showed that LC3 and Beclin-1 were mainly expressed in neurons,and the expression of LC3 and Beclin-1 in Epilepsy group were up-regulated dynamically than that in the control group at 24 h after SE (P<0. 05). Furthermore compared with the Epilepsy group,the expression of LC3 and Beclin-1 in Epilepsy+JWH-133 group were higher but lowered in Epilepsy+AM630 group. Conclusion We demonstrate that CB2R may play a role in autophagy of the hippocampal neurons at the early stage of pilocarpine-induced SE and hinted CB2R may become a treatment target for epilepsy.
Résumé
Objective To investigate the characteristic of movement disorders,so as to improve their diagnosis and treatment. Methods The clini?cal data of patients with movement disorders that admitted in the dystonia and Botox outpatient department were analyzed. Results Cases of involun?tary movement were significantly more than the primary dystonia,and case of primary hemifacial spasm was dominant(163 cases,61.05%). Among the 66 cases of primary dystonia,blepharospasm was ranked the first(19 cases),the second was spasmodic torticollis(18 cases),and the third was Meige syndrome(12 cases).There was no statistical significance in the gender distribution among primary hemifacial spasm,blepharospasm,spas?modic torticollis and Meige syndrome. Instead,there was statistical significance in the treatment methods(P<0.05),and there was statistical signifi?cance in the mean treatment and onset age(P<0.05). Of the 163 cases with primary hemifacial spasm,the mean onset age was 44.22±12.22 years, and the ratio of men to women was 1∶2.4. There were statistical significances in the mean onset age and duration among the patients with different severity degrees(all P<0.05). Conclusion Primary hemifacial spasm,blepharospasm,spasmodic torticollis and Meige syndrome are the com?mon disease in outpatient department. The primary hemifacial spasm is dominant,women are more than men,and the onset age and/or duration are proportional to the severity degree.