氟伐他汀通过抑制活性氧改善氨基核苷嘌呤霉素作用下足细胞β1整合素的表达

Fluvastatin attenuates the down-regulation of β1 integrin expression in PAN-treated podocytes byinhibiting ROS

目的探讨氟伐他汀对氨基核苷嘌呤霉素（PAN）作用下足细胞B1整合素表达的影响及其机制。方法将体外培养的永生化人足细胞分为PAN、不同浓度氟伐他汀、超氧化物歧化酶（SOD）、过氧化氢（H2O2）处理组。用Western印迹和2’，7’-二氯荧光素-3’，6’-二乙酸酯（DCFHDA）法分别检测各组足细胞B1整合素和活性氧（ROS）的表达；噻唑蓝（MTT）法检测足细胞活力。结果PAN和H2O2可显著下调足细胞B1整合素表达，上调ROS表达（均P〈0．05）。低浓度氟伐他汀、SOD可逆转PAN对足细胞的上述作用，显著上调B1整合素、抑制ROS的表达（均P〈0．05）。MTT结果显示PAN、高浓度氟伐他汀、H2O2显著降低足细胞活力（均P〈0．05）；低浓度氟伐他汀、SOD可改善PAN对足细胞活力的影响（均P〈0．05）。结论氟伐他汀可减轻PAN对足细胞的毒性，阻止足细胞B1整合素的下降，其机制可能与抑制PAN介导的ROS升高有关。

Objective To investigate the effect of fluvastatin （FLV） on the expression of β1 integrin in puromycin aminonueleoside （PAN） - treated podocytes and its mechanism. Methods Cultured human podocytes were divided into PAN, different concentrations of fluvastatin （1×10^-8 to 1×10^-5 mol/L） , SOD, H2O2 groups respectively. Expressions of β1 integrin and reactive oxygen species （ROS） in podocytes were detected by Western blotting and DCFHDA （2＇ 7＇ -Dichlorofluoresecein 3＇ 6＇ -diacetate） respectively. The viability of podocyte was determined by MTT colorimetry. Results PAN and H2O2 significantly decreased the expression of β1 integrin and increased the synthesis of ROS in podocytes （P〈0.05 respectively）. Lower concentration fluvastatin or SOD treatment upregulated β1 integrin and down- regulated ROS of podocytes induced by PAN （P〈0.05 respectively）. MTT revealed that lower podocyte viability was found in higher concentration fluvastatin, PAN and H2O2 groups. Lower concentration fluvastatin and SOD could protect podocytes against PAN. Conclusion Fluvastatin attenuates the injury of podocyte induced by PAN and increases the expression of β1 integrin, whose mechanism may be associated with the inhibition of the ROS activity.