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目的观察百草枯(paraquat,PQ)急性染毒大鼠血清细胞因子和氧化应激水平的变化,探讨氯沙坦对大鼠百草枯急性毒性的干预作用。方法选择成年SD大鼠32只,随机分为对照组(NS组)、百草枯(PQ组)以及氯沙坦干预7和14 d组。NS组每天灌胃生理盐水;PQ组为PQ 40 mg/kg一次性灌胃染毒,此后每天灌胃生理盐水;氯沙坦干预7 d组为PQ 40 mg/kg一次性灌胃染毒后,氯沙坦10 mg/(kg·d)连续灌胃给药7 d,此后7 d每天灌胃生理盐水;氯沙坦干预14 d组为PQ40 mg/kg一次性灌胃染毒后,氯沙坦10 mg/(kg·d)连续灌胃给药14 d。各组大鼠分别于第16天采集血样并分离血清,采用酶联免疫吸附法(ELISA)测定大鼠血清中IFN-γ、TNF-α、IL-8、IL-10的含量,用分光光度法测定血清中超氧化物歧化酶(T-SOD)和过氧化氢酶(CAT)活力以及羟自由基(HO·)含量。结果与对照组比较,PQ染毒后大鼠血清中IL-8含量升高(P<0.05),而IL-10和IFN-γ的含量明显降低(P<0.05)。血清中CAT活力和HO·含量升高(P<0.05),T-SOD活力明显降低(P<0.05)。氯沙坦干预7和14 d组IL-8和羟自由基含量、CAT活力以及氯沙坦14 d组仅IL-10和INF-γ含量基本恢复正常(P>0.05);与PQ组比较,氯沙坦干预7和14 d组IL-8和HO·含量以及CAT活力均降低,而IL-10和INF-γ含量逐渐升高(P<0.05)。TNF-α含量和T-SOD活力仅氯沙坦14 d组显著升高(P<0.05)。结论氧化应激及炎症因子可能参与急性PQ中毒过程,且氯沙坦对PQ急性毒性具有一定的逆转作用。
Objective To observe the changes of serum cytokines and oxidative stress in acute paraquat (PQ) -induced rats and explore the intervention of losartan on the acute toxicity of paraquat in rats. Methods Thirty-two adult SD rats were randomly divided into control group (NS group), paraquat (PQ group) and Losartan intervention group (7 and 14 d). The rats in NS group were intragastrically infused with normal saline. The PQ group was treated with PQ 40 mg / kg once a day for gavage. Normal saline was given to rats in NS group. The rats in PQ group received intragastric administration of PQ 40 mg / kg for 7 days. , And losartan 10 mg / (kg · d) for 7 days. After 7 days, losartan was intragastrically administrated with normal saline. After 14-day intervention of losartan, PQ40 mg / kg Saxan 10 mg / (kg · d) continuous oral administration of 14 d. Blood samples were taken from the rats on the 16th day respectively and the serum was separated. The contents of IFN-γ, TNF-α, IL-8 and IL-10 in the serum of the rats were determined by enzyme-linked immunosorbent assay (T-SOD), catalase (CAT) activity and hydroxyl radical (HO ·) content in serum were measured by spectrophotometry. Results Compared with the control group, the levels of IL-8 in serum of PQ-treated rats were significantly increased (P <0.05), while the levels of IL-10 and IFN-γ were significantly decreased (P <0.05). Serum CAT activity and HO · increased (P <0.05), T-SOD activity decreased significantly (P <0.05). IL-8 and hydroxyl radical content, CAT activity, and IL-10 and INF-γ levels in losartan group at 14 d after intervention with losartan were basically normal (P> 0.05). Compared with PQ group, The levels of IL-8 and HO · and the activities of CAT in Losartan intervention group decreased on the 7th and 14th days, while the levels of IL-10 and INF-γincreased (P <0.05). TNF-α content and T-SOD activity were significantly increased in losartan 14 d group (P <0.05). Conclusion Oxidative stress and inflammatory cytokines may be involved in the process of acute PQ poisoning, and losartan may reverse the acute toxicity of PQ.