辛伐他汀对急性百草枯中毒大鼠炎性细胞因子的影响

Effect of pretreatment with simvastatin on inflammatory factor in acute paraquat-intoxicated rats

目的观察辛伐他汀对急性百草枯中毒大鼠炎性细胞因子表达的影响,探讨他汀类药物对急性百草枯中毒大鼠全身炎症反应的抑制作用。方法 72只雌性SD大鼠随机分为对照组、中毒组和辛伐他汀组各24只。百草枯水剂按120mg/kg灌胃大鼠,建立大鼠急性百草枯中毒模型,辛伐他汀组在制备百草枯中毒模型前7d,以辛伐他汀20mg/(kg.d)+生理盐水稀释后灌胃,对照组与中毒组均留置胃管并注射10mL/(kg.d)生理盐水,连续7d,1次/d;于给药后6,24,72h采集血标本,采用ELISA法检测3组大鼠血清白细胞介素(interleukin,IL)-1β、IL-2和肿瘤坏死因子(tumor necrosis factor,TNF)-α水平。结果中毒组给药后6,24h时血清IL-1β水平明显高于对照组(P<0.05),给药后6h时血清IL-2水平明显高于对照组(P<0.05),给药后6,24,72h时血清TNF-α水平高于对照组(P<0.05);辛伐他汀组给药后6,24,72h时血清IL-1β及TNF-α水平明显低于中毒组(P<0.05),给药后6,72h时血清IL-2水平明显低于中毒组(P<0.05)。结论辛伐他汀预处理可抑制急性百草枯中毒大鼠血清TNF-α、IL-1β和IL-2的释放,对急性百草枯中毒大鼠全身炎症反应有一定抑制作用。

Objective To approach the inhibition effect of statins on inflammatory response in acute paraquatintoxicated （PQ） rats by observing the influence of simvastatin on plasma inflammatory factors. Methods Seventy-two healthy SD rats were randomly divided into three groups： control group, PQ group and simvastatin group, with 24 rats in each group. The PQ model was established by gavage of paraquat 120 mg/kg in both groups. The simvastatin group was pretreated with simvastatin （20 mg/（kg .d）） a week before gavage, and PQ group and control group were given normal saline 10 mL/kg by garage, once a day, for totally 7 days. The levels of interleukin-1 beta （IL-1β）, interleukin-2 （IL-2） and tumor necrosis factor-α （TNF-α） in serum were determined 6, 24 and 72 hours after treatment. Results The IL-1β level in serum in 6 and 24 hours, IL-2 level in 6 hours, and TNF-α levels in 6, 24 and 72 hours were higher in PQ group than those in control group （P〈0.05）. Compared with PQ group, the levels of IL-I~ and TNF-α in 6, 24 and 72 hours were lower in simvastatin group than those in PQ group （P^0.05）, and IL-2 level was lower in 6 and 72 hours in simvastatin group than that in PQ group （P^0.05）. Conclusion Simvastatin can inhibit the release of TNF-α, IL-1β and IL-2, and may suppress the systemic inflammatory response in acute PQ rats.