麻黄、五味子影响肺纤维化大鼠血管新生的差异性研究

Difference of influences on angiogenesis between Mahuang (Herba Ephedrae) and Wuweizi (Fructus Schisandrae) in rats with pulmonary fibrosis

目的探讨麻黄、五味子对肺纤维化大鼠血管新生影响差异的作用机制。方法选择SPF级Wistar雄性大鼠90只,随机设立假手术组、模型组、氢化可的松组、麻黄组、五味子组以及麻黄五味子组。采用博莱霉素A5(7 mg/kg)气管滴入方法建立肺纤维化模型,假手术组灌胃生理盐水(6 mL/kg)28 d;中药水煎液浓缩至每毫升含原药材1 g,麻黄组、五味子组分别灌胃麻黄(5 g/kg)、五味子(2.5 g/kg)水煎液28 d,麻黄五味子组灌胃麻黄水煎液(5 g/kg)7 d后灌胃五味子水煎液(2.5 g/kg)至28 d,氢化可地松组肌注氢化可地松20 mg/kg28 d。于7、28 d放射免疫法检测各组大鼠内皮素-1(ET-1)、6-酮-前列腺素F1a(6-Keto-PGF1a)含量变化,免疫组化法观察肺组织微血管密度。结果 7 d时,模型组血浆ET-1含量升高,较假手术组差异有统计学意义(P<0.05),6-Ke-to-PGF1a含量较假手术组有所升高,但差异无统计学意义;28 d时,麻黄五味子组与氢化可的松组血浆ET-1含量显著降低,与模型组比较差异有统计学意义(P<0.05),各治疗组6-Keto-PGF1a含量较7 d时均有所升高。模型组肺微血管密度显著多于假手术组及各治疗组(P<0.05),麻黄组对肺小动脉血管新生的抑制高于五味子组、麻黄五味子组。结论麻黄对改善肺纤维化大鼠肺系数有积极作用,麻黄、五味子联合应用对肺纤维化的肺部小动脉损伤有抑制作用。

Objective To observe the difference of influences on angiogenesis between Mahuang（Herba Ephedrae） and Wuweizi（Fructus Schisandrae） in rats with pulmonary fibrosis,and discuss the mechanism.Methods Wistar rats of SPF level（n=90） were chosen and divided randomly into the sham-operation group,model group,hydrocortisone group,Mahuang group,Wuweizi group and combined group of Mahuang and Wuweizi（combined group）.The model of pulmonary fibrosis was established by using tracheal instillation of bleomycin A5（7 mg/kg）.The sham-operation group was given normal saline solution intragastrically（6 mL/kg） for 28 days.Mahuang decoction or Wuweizi decoction were concentrated to the decoction with 1 g original medicinal in 1 mL.The Mahuang group was given Mahuang decoction intragastrically（5 g/kg） for 28 days,Wuweizi group was given Wuweizi decoction intragastrically（2.5 g/kg） for 28 days,combined group was given intragastrically Mahuang decoction（5 g/kg） for 7 days and then Wuweizi decoction（2.5 g/kg） until 28th days,and hydrocortisone group was injected intramuscularly hydrocortisone（20 mg/kg） for 28 days.The samples were collected on the 7th and 28th day.The content changes of endothelin-1（ET-1） and 6-Keto-PGF1a were detected by using radioimmunoassay,and pulmonary microvessel density（MVD） was observed by applying immunohistochemistry.Results On the 7th day,the plasma content of ET-1 increased in the model group compared with the sham-operation group（P〈0.05）,and the content of 6-Keto-PGF1a increased too but had no significance compared with the sham-operation group.On the 28th day,the plasma content of ET-1 decreased significantly in the combined group and hydrocortisone group compared with the model group（P〈0.05）.The content of 6-Keto-PGF1a increased in all medicinal groups on the 28th day than those on the 7th day.MVD in the model group was higher than that in the sham-operation group and all medicinal groups（P〈0.05）,and the Mahuang group showed higher inhibitory effect in the angiogenesis of pulmonary arteriola than the Wuweizi group and combined group.Conclusion Mahuang has an active effect in the relief of lung coefficients in rats with pulmonary fibrosis.The combined use of Mahuang and Wuweizi has an inhibitory effect on the lesion of pulmonary arteriola.