氯沙坦对百草枯急性染毒大鼠肺组织氧化损伤的影响

Intervention of losartan on lung oxidative injury induced by paraquat in rats

目的探讨氯沙坦对百草枯(PQ)急性染毒大鼠肺组织氧化损伤的影响。方法选择成年雄性SD大鼠随机分为正常对照组、PQ染毒组(一次性ig给予PQ 40 mg·kg-1)及染毒后氯沙坦干预7和14 d组(一次性ig给予PQ后,每天ig给予氯沙坦10 mg·kg-1连续7和14 d)。第16天处死大鼠取肺组织,常规制备肺组织病理切片,HE染色观察肺组织病理改变。用分光光度法测定肺组织匀浆中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及总抗氧化能力(T-AOC)和脂质过氧化物(LPO)含量。采用实时荧光定量PCR检测肺组织NF-κB mRNA表达水平。结果病理观察结果显示,PQ急性染毒后大鼠出现明显的肺损伤和肺组织纤维化,经氯沙坦干预后病理改变均有一定程度的逆转。与正常对照组比较,PQ染毒组大鼠肺组织匀浆中SOD和CAT活性明显降低(P<0.05),T-AOC下降(P<0.05),LPO含量明显升高(P<0.05)。与PQ染毒组比较,氯沙坦干预7和14 d组SOD和CAT活性及T-AOC升高(P<0.05),LPO含量明显降低(P<0.05),其中氯沙坦干预7和14 d组T-AOC和LPO含量以及氯沙坦干预14 d组SOD和CAT活性基本恢复接近至正常水平。实时荧光定量PCR结果表明,PQ染毒后肺组织NF-κB mRNA表达水平明显升高(P<0.05)。与PQ染毒组比较,氯沙坦干预7和14 d组NF-κB mRNA表达降低(P<0.05),恢复接近正常水平。结论氧化应激参与PQ急性肺损伤过程,氯沙坦通过提高肺组织的抗氧化能力和降低NF-κB mRNA表达而发挥对肺组织的保护作用。

OBJECTlVE To expIore the intervention effect of Iosartan on the Iung oxidative injury in-duced by paraquat（PQ）. METHODS Adult male SD rats were randomIy divided into 4 groups：normal control group,PQ intoxication group（rats were treated with singIe ig PQ 40 mg·kg-1 ）,Iosartan inter-vention for 7 and 14 d groups（rats were ig given Iosartan 10 mg·kg-1 daiIy for 7 and 14 consecutive days after PQ was given）. AII rats were sacrificed on the 16th day to obtain Iung tissues. HE staining was used to observe the Iung pathological changes. The activities of superoxide dismutase（SOD）,catalase （CAT）and total antioxidant capacity（T-AOC）and content of Iipid peroxide（LPO）were detected by spectrophotometry. Real-time quantitative PCR was used to investigate the NF-κB mRNA expression in Iung tissue. RESULTS Pathological examination showed that acute Iung injury and significant Iung fibro-sis appeared in PQ intoxication group but were reversed by Iosartan. The Ievels of SOD,CAT and T-AOC decreased whiIe the content of LPO in PQ intoxication group increased significantIy compared with control group（P﹤0.05）. Compared with PQ intoxication group,the Ievels of SOD,CAT and T-AOC in-creased and the content of LPO decreased in Iosartan intervention for 7 and 14 d groups（P﹤0.05）,and the Ievels of T-AOC and LPO in Iosartan intervention for 7 and 14 d groups and the activities of SOD and CAT in Iosartan intervention for 14 d group nearIy returned to normal. The mRNA expression of NF-κB was upregulated after rats were exposed to PQ,downregulated in Iosartan intervention for 7 and 14 d groups in rat Iung tissues（ P﹤0.05）,but nearIy returned to normal. CONCLUSlON Oxidative stress may be involved in the acute PQ poisoning process and Iosartan might have intervention effect on acute PQ Iung damage by improving the antioxidant capacity and downregulating the mRNA expression of NF-κB.