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江伟,温恩懿,龚敏,瞿平,毕杨,张赟,魏小平,刘友学,陈洁,李廷玉.ATRA和9-cis-RA对缺氧缺糖损伤PC12细胞凋亡的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(24):2595-2598.
Jiang Wei,Wen Enyi,Gong Min,Qu Pin,Bi Yang,Zhang Yun,Wei Xiaoping,Liu Youxue,Chen Jie,Li Tingyu.Effect of all-trans retinoic acid and 9-Cis-RA on apoptosis of PC12 cells after oxygen and glucose-deprivation injury[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(24):2595-2598.
江伟,温恩懿,龚敏,瞿平,毕杨,张赟,魏小平,刘友学,陈洁,李廷玉.ATRA和9-cis-RA对缺氧缺糖损伤PC12细胞凋亡的影响[J].陆军军医大学学报(原第三军医大学学报),2010,32(24):2595-2598. DOI:
Jiang Wei,Wen Enyi,Gong Min,Qu Pin,Bi Yang,Zhang Yun,Wei Xiaoping,Liu Youxue,Chen Jie,Li Tingyu.Effect of all-trans retinoic acid and 9-Cis-RA on apoptosis of PC12 cells after oxygen and glucose-deprivation injury[J].J Amry Med Univ (J Third Mil Med Univ),2010,32(24):2595-2598. DOI:
目的 探讨不同构型视黄酸[全反式视黄酸(all-trans retinoic acid
ATRA);9顺式视黄酸(9-cis-retinoic acid
9-Cis-RA)]对缺氧缺糖损伤的PC12细胞凋亡的影响,且通过何种受体途径作用。 方法 实验分组为:未刺激组(0 μmol/L RA);1、5、10 μmol/L,20 μmol/L ATRA;1、5、10、20 μmol/L 9-CisRA。倒置显微镜观察缺氧缺糖损伤前后细胞形态变化,流式细胞术研究经不同浓度ATRA和9-Cis-RA刺激的缺氧缺糖损伤PC12细胞凋亡水平。ELISA监测ATRA和9-Cis-RA处理4 h后PC12细胞的LDH释放水平以了解其细胞膜损伤水平的差异。 结果 ATRA组细胞凋亡率在1 μmol/L 浓度时与未刺激组无显著差异(P0.05),从5 μmol/L起随着浓度的增高凋亡率显著增高(P0.05),在10、20 μmol/L 浓度组均显著高于相同浓度的9-Cis-RA组(P0.05)和未刺激组(P0.05);而9-Cis-RA在20 μmol/L组凋亡率低于未刺激组,但无显著性差异(P0.05)。乳酸脱氢酶(LDH)释放水平在ATRA刺激组从5 μmol/L起随浓度的增高而显著性增高(P0.01),在5、10、20 μmol/L浓度均显著高于未刺激组和9-Cis-RA组(P0.05),而在各浓度9-Cis-RA组与未刺激组均无显著性差异(P0.05)。在RA信号系统中ATRA特异激活retinoic acid receptors (RARs)
而9-Cis-RA同时激活RARs和retinoid X receptors (RXRs)。 结论 在缺氧缺糖损伤的PC12细胞ATRA可通过激活RARs受体途径发挥促凋亡效应,但这种效应可以被激活RXRs受体途径而抑制。
Objective To investigate the effect of different retinoic acid (RA) configurations
all-trans retinoic acid (ATRA) and 9-Cis-RA on apoptosis of PC12 cells after oxygen and glucose-deprivation (OGD) injury
and explore the receptor pathway involved in. Methods Cell morphology before and after OGD injury was observed with inverted microscopy
and the apoptotic rate of PC12 cells treated with different concentrations of ATRA and 9-Cis-RA was studied by flow cytometr after OGD injuryy. Finally
LDH release from PC12 cells was measured by ELISA after 4 hours’ RA treatment for degree of membrane damage. There were 9 groups: A (0 μmol/L RA); B (1 μmol/L ATRA); C (1 μmol/L 9-CisRA); D (5 μmol/L ATRA); E (5 μmol/L 9-CisRA); F (10 μmol/L ATRA); G (10 μmol/L 9-CisRA); H (20 μmol/L ATRA); I (20 μmol/L 9-CisRA). Results ATRA at a dose of 1 μmol/L had no effect on the apoptosis of PC12 cells after OGD injury
as the cells without RA treatment (P0.05). But the apoptotic rate were significant increasing when the concentration of ATRA was elevated from 5 μmol/L to 20 μmol/L (P0.05). The apoptotic rates in 10 and 20 μmol/L groups were significantly higher than those of the 9-Cis-RA groups with same stimulus concentration (P0.05) and 0 μmol/L group (P0.05). However
the apoptotic rate in 20 μmol/L 9-Cis-RA was lower than that of 0 μmol/L group (P0.05)
but was not significantly. The levels of LDH release of ATRA stimulation groups were significantly increasing from 5 μmol/L with the concentration rising (P0.01)
and were significantly higher than that of control and 9-Cis-RA stimulation groups (P0.05). There was no significant difference in LDH release between 0 μmol/L group
and each 9-Cis-RA group (P0.05). Conclusion ATRA improves the apoptosis of PC12 cells after OGD injury through activating retinoic acid receptors (RAR)
while this effect might be inhibited by 9-Cis-RA via retinoid X receptors (RXRs).
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