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目的观察百草枯急性染毒大鼠肺组织细胞因子水平的变化,探讨氯沙坦对大鼠百草枯急性肺损伤的干预作用。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和14 d。各组分别于第15d处死并取肺组织,常规制备肺组织病理切片,苏木素-伊红(HE)染色后光学显微镜观察肺组织病理学改变。制备组织匀浆并离心取上清液,采用酶联免疫吸附法(ELISA)测定大鼠肺组织中IFN-γ、TNF-α、IL-8、IL-10的含量。结果 (1)病理检查结果显示,PQ急性染毒后大鼠肺泡间隔弥漫性显著增宽,部分区域可见炎性细胞浸润,间质小血管壁增厚,经氯沙坦干预后病理改变有一定程度的逆转。(2)与NS组比较,PQ染毒后大鼠肺组织中IL-8和TNF-α含量升高(P<0.05),而IL-10和IFN-γ的含量明显降低(P<0.05)。与PQ组比较,氯沙坦干预7和14 d组IL-8、TNF-α、IL-10和INF-γ含量均逐渐升高(P<0.05);与NS组比较,氯沙坦干预7和14 d组IL-10和INF-γ含量基本恢复正常(P>0.05)。结论炎症因子可能参与PQ急性肺损伤过程,且氯沙坦对PQ引起的肺组织炎性因子异常改变具有一定的逆转作用。
Objective To observe the changes of cytokines in the lungs of acute paraquat-exposed rats, and to explore the intervention of losartan in acute lung injury of paraquat in rats. Methods Thirty-two adult SD rats were randomly divided into control group (NS group), paraquat (PQ) group and losartan group (7 and 14 d). The rats in NS group were given gavage daily with normal saline. PQ group was treated with PQ 40 mg / kg once a day for gavage, and normal saline was given daily. In losartan group, PQ 40 mg / kg Saxan 10 mg / kg · d continuous gavage 7 and 14 d. The rats in each group were sacrificed on the 15th day and the lungs were taken out. The lungs were routinely prepared for histopathology. The pathological changes of the lungs were observed by light microscopy after hematoxylin and eosin staining. The tissue homogenates were prepared and the supernatant was centrifuged. The contents of IFN-γ, TNF-α, IL-8 and IL-10 in the lung tissue were determined by enzyme-linked immunosorbent assay (ELISA) Results (1) The results of pathological examination showed that after acute exposure to PQ, the diffuse alveolar septa of rats were significantly broadened, infiltration of inflammatory cells was observed in some areas, and thickened interstitial small blood vessel wall. The pathological changes after intervention with losartan were definite The degree of reversal. (2) Compared with NS group, the levels of IL-8 and TNF-αin lung tissues of PQ-treated rats were significantly increased (P <0.05), while the levels of IL-10 and IFN- . Compared with PQ group, the levels of IL-8, TNF-α, IL-10 and INF-γ in Losartan intervention group were significantly increased at 7 and 14 d (P <0.05); Compared with NS group, Losartan intervention 7 The levels of IL-10 and INF-γin the 14th and 14th days were basically normal (P> 0.05). Conclusion Inflammatory cytokines may be involved in the process of acute lung injury induced by PQ, and losartan may reverse the abnormal changes of inflammatory factors induced by PQ in lung tissues.