Effects of combination of pioglitazone and rosuvastatin on rat adventitial fibroblasts oxidization and inflammation induced by Ang Ⅱ
TAO Yang-chen1, MIAO Pei-zhi2, ZHAO Li-fang2, GAO Ping-jin3, GU Shui-ming2
(1.School of Clinical Medicine，Jiangsu University, Zhenjiang Jiangsu 212001；2.Department of Cardiology, Xuhui District Central Hospital, Shanghai 200031; 3.Institute of Hypertension, Ruijin Hospital, Shanghai 200031, China)
Abstract：Objective: To investigate the effect and possible mechanism of peroxisome proliferators activated receptor(PPAR) γ agonists pioglitazone and rosuvastatin on rat aortas adventitial fibroblasts (AFs) oxidization and inflammation. Methods: Adventitial fibroblast(AF) were prepared from rat aortas using explant technique and cultured for passages. The fourth passage were used and into five groups: the control group, AngⅡ group, pioglitazone group, rosuvastatin group, pioglitazone and rosuvastatin group. The effects of AngⅡ on the NADPH oxidase subunits with or without rosuvastatin and pioglitazone were investigated by Western-blot. The levels of transcription factors NF-κB and activator protein-1(AP-1) were measured by electrophoretic mobility shift assay. PPARγ mRNA level was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). Results: ① AngⅡ induced the expressions of NADPH oxidase subunits p22phox and p67phox(P<0.01). PPARγ agonists pioglitazone alone or the combination with rosuvastatin inhibited these effects by AngⅡ(P<0.05). ② AngⅡ stimulated the activations of transcription factors NF-κB and AP-1, pioglitazone reduced NF-κB, rosuvastatin reduced AP-1, and the combination of pioglitazone and rosuvastatin reduced both NF-κB and AP-1 at the same time. ③ Pioglitazone and rosuvastatin alone or the combination induced the expression of PPARγ mRNA (P<0.01). The combination had the further effect(P<0.05). Conclusion: The combination of pioglitazone and rosuvastatin may further inhibit the oxidant and inflammatory effects on rat AFs induced by AngⅡ, which may be mediated with upregulating PPARγ mRNA level by statins.
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2013, Vol. 23 
