百草枯中毒大鼠急性肺损伤机制及姜黄素的干预研究

目的探讨急性百草枯中毒大鼠肺组织氧化应激及脂质过氧化损伤机制及姜黄素的干预作用。 方法将120只成年雄性SD大鼠按不同造模方法用随机数字表法分成对照组、百草枯中毒组、姜黄素干预组，每组大鼠40只。百草枯中毒组腹腔注射百草枯15 mg/kg，姜黄素干预组腹腔注射姜黄素200 mg/kg，15 min后腹腔注射百草枯15 mg/kg，对照组腹腔注射等容量的生理盐水。百草枯中毒组及姜黄素干预组于染毒后（对照组于腹腔注射后）3 h、6 h、24 h、3 d、7 d分别随机抽取8只大鼠取材。荧光实时定量PCR法测定各组大鼠肺组织中的转化生长因子（TGF）-β₁ mRNA的表达量，硫代巴比妥酸比色法、分光光度计比色法、黄嘌呤氧化酶法分别测定肺组织匀浆中丙二醛、髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）活性，光镜下观察各组肺组织病理变化。 结果染毒后6 h、24 h、3 d、7 d，与对照组相比，百草枯中毒组和姜黄素干预组肺组织TGF-β₁ mRNA的表达量明显升高（F = 136.928、32.282、52.008、30.940，P均< 0.05），丙二醛（F = 132.896、64.988、30.622、30.192）、MPO（F = 34.738、202.578、122.019、119.626）含量升高（P均< 0.05），而SOD活力降低（F = 34.738、202.578、122.019、119.626，P均< 0.05）；与百草枯中毒组相比，姜黄素干预组各时间点肺组织TGF-β₁ mRNA表达量、丙二醛及MPO含量均降低（P均< 0.05），肺组织SOD活力均升高（P均< 0.05）。 结论氧化应激及细胞膜脂质过氧化过程的启动可能是百草枯中毒急性肺损伤的机制之一，姜黄素可能通过阻止该过程减轻肺损伤的程度。

Mechanism of acute lung injury induced by paraquat and the intervention effect of curcumin in rats

ObjectiveTo observe the oxidative stress and lipid peroxidation damage in lung of rats with acute paraquat (PQ) poisoning, and investigate the intervention effect of curcumin on it. MethodsTotally 120 adult male Sprague-Dauley rats in the study were divided into the control, PQ-poisoned and curcumin-intervened groups (40 rats in each group). Rats in the PQ-poisoned group were intraperitoneally (i.p.) administered with PQ (15 mg/kg). Curcumin 200 mg/kg was injected i.p. at 15 min before administered with PQ (15 mg/kg, i.p.) in rats of the curcumin-intervened group. The same (15 mg/kg, i.p.) in rats of the curcumin-intervened group. The same volume of saline were injected i.p. in rats of the control group. Eight rats from each group were sacrificed at 3 h, 6 h, 24 h, 3 d, and 7 d after poisoning, respectively. The expression of TGF-β₁ mRNA in lungs of rats were measured with fluorescence real-time quantitative PCR. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) in lung of rats were measured with thiobarbituric acid colorimetric, spectrophotometer colorimetry and xanthine oxidase method, respectively. Pathological changes in lung were observed by light microscope. ResultsCompared with the control group, TGF-β1 mRNA expression in lung of rats increased significantly at 6 h, 24 h, 3 d, and 7 d after PQ poisoning (F = 136.93, 32.28, 52.01, 30.94; all P < 0.05), the levels of MDA (F = 132.896, 64.988, 30.622, 30.192) and MPO(F = 34.738, 202.578, 122.019, 119.626) increased obviously (all P < 0.05), but the SOD level decreased remarkably in the PQ-poisoned group and curcumin-intervened group (F = 34.738, 202.578, 122.019, 119.626; all P < 0.05). When compared with the PQ-poisoned group, the levels of TGF-β1 mRNA expression, MPO and MDA in lung of rats in the curcumin-intervened group decreased significantly and the level of SOD in the curcumin-intervened group increased statistically at 6 h, 24 h, 3 d, and 7 d after PQ poisoning (all P < 0.05). ConclusionsThe initiation of oxidative stress and lipid peroxidation of cell membrane may be one of the mechanisms of acute lung injury in rats with PQ poisoning. The curcumin may reduce the lung injury in rats by inhibiting it.