贝母素乙对肺纤维化大鼠肺组织MEK1/2、ERK1/2及其磷酸化的影响
Effect of Peiminine on MEK1/2， ERK1/2 and the Phosphorylatioin in Lung Tissue of Pulmonary Fibrosis in Rats
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摘要: 目的 探讨贝母素乙对博莱霉素致肺纤维化大鼠肺组织MEK1/2、ERK1/2及其磷酸化的影响。方法 大鼠麻醉后，经气管软骨环间隙向心端穿刺，注入博莱霉素5 mg/kg建立大鼠肺纤维化模型，假手术组大鼠在同样麻醉条件下气管内注入等容积生理盐水。术后第2天开始每天灌胃给药，假手术组和模型组给予蒸馏水，地塞米松组给予等容积地塞米松蒸馏水溶液，贝母素乙A组、B组分别给予等容积贝母素乙5、2.5 mg/kg蒸馏水溶液。灌胃28 d后，麻醉并颈动脉取血后处死大鼠，肺组织固定，包埋切片，常规脱蜡，行免疫组化SABC法检测肺组织MEK1/2、ERK1/2水平，Western blot法检测p-MEK1/2、p-ERK1/2水平。结果 贝母素乙可显著降低肺纤维化大鼠的肺组织ERK1/2、MEK1/2水平(P<0.01)，与地塞米松作用相似（P>0.05），贝母素乙A组、B组之间比较未见明显差异（P>0.05）。贝母素乙可以显著降肺纤维化大鼠的肺组织p-MEK1/2、p-ERK1/2水平（P<0.01)，较地塞米松更为显著（P<0.01)，贝母素乙B组较贝母素乙A组更为显著（P<0.01）。结论 贝母素乙减轻博莱霉素致肺纤维化大鼠的MEK1/2、ERK1/2及其磷酸化水平可能是其抗纤维化的作用机理之一。Abstract: OBJECTIVE To investigate the effect of peiminine on MEK1/2， ERK1/2 and the phosphorylatioin of bleomycin-induced pulmonary fibrosis in rats. METHODS Bleomycin of 5 mg/kg was instilled into the rats with a microliter injector to induce the acute lung injury. Shamoperated group and control group were given distilled water of 1 mL/100 g. Dexamethasone group was given equal volume of dexamethasone distilled water solution. Peiminine A and B group were given equal volume of peiminine distilled water solution of 5 mg/kg and 2.5 mg/kg， respectively. After consecutive daily gavage for 28 d， the rats were anesthetized and killed by carotid exsanguination. Lungs were fixed and embedded， and 4 μm sections were prepared. MEK1/2 and ERK1/2 in the lung tissues were detected by immunohistochemistry. The p-MEK1/2 and p-ERK1/2 were detected by Western blot. RESULTS Peiminine significantly reduced the levels of ERK1/2 and MEK1/2 in lung tissues of rats with bleomycin-induced pulmonary fibrosis(P<0.01)， and the effects was similar to dexamethasone (P>0.05). No significant difference was observed between peimine A group and B group(P>0.05). Compared to the model group and dexamethasone group， peiminine significantly reduced the level of p-MEK1/2 and p-ERK1/2 in lung tissue of bleomycin-induced pulmonary fibrosis rats(P<0.01). Compared to peimine A group， the B group displayed more significant efficacy(P<0.01). CONCLUSION Peiminine attenuates the level of MEK1， ERK1 / 2 and the phosphorylation in lung tissues of bleomycin-induced pulmonary fibrosis rats， which may be one of the mechanism of antifibrosis.
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