Abstract:

Objective：To investigate the effects and possible mechanism of fluvastatin（FLV） on expression of β1 integrin in PAN-treated podocytes.  Methodology：Cultured human podocytes were divided into 4 groups：They were ①normal control group; ②DMSO（1mg/ml） control group; ③PAN (1.0ug/ml) group：PAN treated podocytes for 12h, 24h, 48h, and 72h respectively; and ④PAN(1.0ug/ml) +FLV(1×10-8～1×10-5 M) group: podocytes were treated with PAN plus different concentrations of FLV for 48h. The expression of β1 integrin and reactive oxygen species (ROS) in all groups was detected by Western Bolt and DCFHDA (2’7’-Dichlorofluoresecein 3’6’-diacetate) respectively. Podocytes were also divided into 5 groups to determine the cellular viability by MTT colorimetry at 12h, 24h, 48h, and 72h respectively.  Results：Compared with the normal control group, the expression of β1 integrin decreased significantly in podocytes treated with PAN at the time of 24h, 48h, and 72h（P<0.05）, while the synthesis of ROS increased definitely（P<0.05）. Fluvastatin significantly upregulated the expression of β1 integrin and down regulated ROS at the concentration of 1×10-7 M（P<0.05）.The expression of β1 integrin had an inverse correlation with the synthesis of ROS in PAN group and PAN+FLV group. The results of MTT revealed that DMSO and lower concentration of fluvastatin (1×10-8M and 1×10-7M) had no significant effect on viability of podocyte（P>0.05), while lower podocyte viability was found in higher concentration of fluvastatin (1×10-6M and 1×10-5M) group, PAN group and PAN+FLV group at 24h（P<0.05）. Compared with the PAN group, the viability of podocyte was improved significantly in PAN+FLV group when the concentration of fluvastatin was 1×10-7 M（P<0.05）at the time of 48h. Conclusion：The expression of β1 integrin was decreased in PAN-treated podocytes, which was improved by treating with fluvastatin . The mechanism may be associated with inhibiting the activity of ROS.