阿托伐他汀对百草枯致心肌纤维化和氧化应激的影响

Effect of atorvastatin on paraquat-induced myocardial fibrosis and oxidative stress

目的探讨心肌纤维化及氧化应激是否参与了百草枯导致的心肌损伤，以及阿托伐他汀能否减轻这种损伤。方法将50只SD大鼠随机分为5组：单纯染毒组、低剂量治疗组、中剂量治疗组、大剂量治疗组、正常对照组。前四组大鼠以80mg／kg百草枯溶液灌胃1h后，分别以生理盐水及阿托伐他汀20、40、80mg／kg连续灌胃7d。正常对照组以生理盐水连续灌胃7d。7d后取大鼠心肌组织，比色法测定超氧化物歧化酶（SOD）和丙二醛（MDA）的含量，RT—PCR法测定心肌中转化生长因子-β1（TGF—β1）和α-平滑肌肌动蛋白（α—SMA）的mRNA转录水平。结果单纯染毒组的TGF-β1和α-SMA的mRNA转录水平高于其他各组（P〈0．05）；治疗组较单纯染毒组有明显降低，治疗剂量越大，TGF-β1和α-SMA的mRNA转录水平越低（P〈0．05）。单纯染毒组SOD活力低于其他各组，而MDA含量升高（P〈0．05）；治疗组较单纯染毒组SOD活力升高，MDA含量下降（P〈0．05），但组间比较差异无统计学意义。结论心肌纤维化及氧化应激参与了百草枯导致的心肌损伤，阿托伐他汀可以减轻这种损伤。

Objective To investigate the roles of myocardial fibrosis and oxidative stress in the process of paraquat-induced myocardial injury, and whether atorvastatin can reduce this myocardial inju-ry. Methods Fifty SD rats were randomly divided into five groups： normal control group, simple ex-posure group（ PQ group）, low-dose treatment group （ LDT group）, medium-dose treatment group （MDT group） and high-dose treatment group （HDT group）. Normal control group were fed with warm saline once per day. The other four groups were fed with paraquat （80 mg/kg） , and after 1 h they were respectively fed with saline, atorvastatin 20 mg/kg, 40 mg/kg and 80 mg/kg each day. After 7 days, all rats＇ myocardium were harvested. The contents of superoxide dismutase （SOD） and malonaldehyde（MDA） in rats＇ myocardium were tested by colori-metric determination. The transcription levels of TGF-151 and α-smooth muscle actin（α-SMA） mR-NA in the myocardium were tested by RT-PCR. Results The transcription levels of TGF-β1 and α-SMA in rats＇ myocardium of PQ group were significantly higher than those of normal control group （ P 〈 0.05 ） , but lower than those of the three treatment groups （ P 〈 0.05 ）. The SOD contents of PQ group was significantly lower than that of normal control group （ P 〈 0.05 ） , but higher than that of the three treatment groups（ P 〈 0.05 ） , while the MDA contents was just the reverse（ P 〈 0.05 ）. Conclusions Myocardial fibrosis and oxidative stress take part in the process of paraquat-induced myocardial injury; atorvastatin can reduce paraquat-induced myocardial injury of rats, which may be related to improvement of tissue antioxidant capacity and reduce of mRNA transcription of TGF-β1 and α-SMA.