目的：探讨维甲酸受体（ RAR）在足细胞损伤中的作用。方法体外培养足细胞随机分为正常组和模型组，待6孔板足细胞融合90％后正常组在正常培养基培养24 h，模型组在含0．15μg／ml阿霉素（ ADR）的培养基中培养24 h建立损伤模型。造模后，光镜、电镜检查足细胞形态，实时荧光定量PCR和Western blot方法检测足细胞nephrin、podocin、转化生长因子β1（ TGF-β1）、α-平滑肌肌动蛋白（α-SMA ）、维甲酸受体α、β和γ（ RAR-α，β，γ）的mRNA及其蛋白表达变化。结果（1）与正常组比较，光镜下模型组足细胞肥大和细胞碎片增多，电镜下部分足细胞萎缩，足突融合、回缩，甚至消失；（2）与正常组比较，模型组足细胞的nephrin和podocin 的mRNA及其蛋白表达均显著降低（P均＜0．05），TGF-β1和α-SMA的mRNA及其蛋白表达均显著增高（P均＜0．05），RAR-α和RAR-γ的mRNA及其蛋白表达均显著下调（P均＜0．05），而RAR-β的mRNA及其蛋白表达无显著改变（P均＞0．05）；（3）模型组足细胞的RAR-α和RAR-γ蛋白表达与nephrin，podocin蛋白表达均呈显著正相关，与TGF-β1和α-SMA蛋白表达均呈显著负相关。结论在阿霉素致足细胞损伤中，足细胞的RAR-α和RAR-γ表达均显著降低，可能参与了足细胞损伤的发生发展。%Objective To investigate the effect of retinoic acid receptors (RARs) on injured podocytes induced by adriamycin(ADR).Methods Podocytes cultured in vitro were randomly divided into normal group and model group ,the former group was cultured in normal medium for 24 hours following the 6-well-plate podocytes fusion had achieved 90%,the latter group was suffered to ADR (0.15μg/ml) for 24 hours to establish injury model .Morphological changes were observed under light and electron microscope.Nephrin,podocin,transforming growth factor β1(TGF-β1),α-smooth muscle actin (α-SMA) and retinoic acid receptors (RAR-α,β,γ) mRNA and protein levels in podocytes were measured by RT-PCR and Western blot .Results ①Compared with normal group ,there were increased cell debris and hypertrophy observed under light microscope as well as shrinking of podocytes structure and foot processes fusion ,retraction ,even disappearing observed under electron microscope in the model group .② The levels of mRNA and protein of nephrin ,podocin,RAR-α,RAR-γdecreased significantly in the model group in contrast with those in the normal group (all P<0.05),while the levels of mRNA and protein of TGF-β1 and α-SMA increased significantly (all P<0.05).However,there were no significant differences in RAR-βmRNA and protein expressions between two groups(all P>0.05).③RAR-αand RAR-γprotein expressions positively correlated with nephrin and podocin protein expressions but negatively correlated with TGF-β1,α-SMA protein expressions in the model group(P<0.05).Conclusion The lower expressions of RAR-αand RAR-γin injured podocytes induced by adriamycin suggests that they might play an important role in the injury process of podocytes .
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