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目的观察肺间质纤维化大鼠氧化/抗氧化状态、外周血单个核细胞(PBMCs)DNA损伤情况及苦参碱的保护作用机制。方法采用气管内灌注博来霉素(BLM)的方法建立大鼠肺纤维化模型,设正常对照组、模型组、小剂量苦参碱组、大剂量苦参碱组和氢化可的松组,每组18只,再各分为第7天、第14天和第28天组。观察各组不同时期病理切片和肺组织羟脯氨酸(HYP)浓度;测定肺组织丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)含量;用荧光显微镜检测PBMCsDNA损伤情况。结果苦参碱组和氢化可的松组的肺泡炎和肺纤维化程度及HYP含量显著地低于模型组(P<0.05);苦参碱和氢化可的松能明显减少肺间质纤维化大鼠肺组织MDA水平,提高GSH-Px含量,降低PBMCs彗星率(P<0.01)。结论苦参碱能减轻BLM诱导的大鼠肺纤维化,这种作用有可能通过改善BLM大鼠体内氧化应激状态,减轻肺间质纤维化大鼠PBMCsDNA损伤实现的。
Objective To observe the oxidative/antioxidative status, DNA damage of peripheral blood mononuclear cells (PBMCs) and protective mechanism of matrine in rats with pulmonary fibrosis. Methods Pulmonary fibrosis model was established by intratracheal instillation of bleomycin (BLM). The normal control group, model group, low-dose matrine group, high-dose matrine group, and hydrocortisone group were established. Each group consisted of 18 animals and each group was divided into 7th, 14th, and 28th days groups. The hydroxyproline (HYP) concentration in lung tissue was observed at different stages of each group; the content of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in lung tissue were measured; DNA damage of PBMCs was detected by fluorescence microscope. Happening. Results The levels of alveolitis and pulmonary fibrosis and HYP levels in the matrine group and hydrocortisone group were significantly lower than those in the model group (P<0.05). Matrine and hydrocortisone significantly reduced pulmonary interstitial fibrosis. The level of MDA in rat lung tissue increased GSH-Px content and decreased PBMCs comet rate (P<0.01). Conclusion Matrine can reduce BLM-induced pulmonary fibrosis in rats. This effect may be achieved by improving oxidative stress in BLM rats and reducing PBMCs DNA damage in rats with pulmonary interstitial fibrosis.