【摘要】 目的:观察积雪草苷对平阳霉素诱导的大、小鼠肺纤维化的保护作用,并探讨其作用机制。方法:（1）小鼠实验:将KM小鼠随机分为对照组、模型组、阳性对照（醋酸泼尼松,5 mg/kg）组和积雪草苷低剂量（40 mg/kg）、高剂量（80 mg/kg）组,每组10只。除对照组外,其他各组小鼠采用一次性气管注入平阳霉素（5 mg/kg）的方法诱导肺纤维化模型。造模次日,各组灌胃给予相应的药物干预,连续28 d。末次给药后,分离肺组织;测定肺指数;ELISA检测肺组织白介素（IL）-6、肿瘤坏死因子-α（TNF-α）、IL-1β含量;PCR检测肺组织转化生长因子-β₁（TGF-β₁）mRNA表达。（2）大鼠实验:将SD大鼠随机分为对照组、模型组、阳性对照（醋酸泼尼松,4 mg/kg）组和积雪草苷低剂量（20 mg/kg）、高剂量（40 mg/kg）组,每组10只。除对照组外,其他各组大鼠采用一次性气管注入平阳霉素（5 mg/kg）的方法诱导肺纤维化模型。造模次日,各组灌胃给予相应的药物干预,连续28 d。末次给药后,分离肺组织;测定肺指数;HE染色后光镜下观察各组大鼠肺组织形态学变化;ELISA检测肺组织IL-6、TNF-α、IL-1β含量;PCR检测肺组织TGF-β₁mRNA表达。结果:（1）小鼠实验:模型组小鼠肺指数,肺组织IL-6、TNF-α、IL-1β含量及TGF-β₁mRNA表达均较对照组显著升高（P<0.01）。与模型组相比,阳性对照组与积雪草苷低、高剂量组小鼠的肺指数及肺组织IL-6、TNF-α、IL-1β含量显著降低（P<0.05,P<0.01）,积雪草苷低、高剂量组小鼠肺组织TGF-β₁mRNA表达水平显著降低（P<0.05）。（2）大鼠实验:模型组大鼠肺指数,肺组织IL-6、TNF-α、IL-1β含量及TGF-β₁mRNA表达均较对照组显著升高（P<0.01）。与模型组相比,阳性对照组与积雪草苷低、高剂量组大鼠肺指数显著降低（P<0.05,P<0.01）,肺组织TGF-β₁mRNA表达水平显著降低（P<0.01）;阳性对照组和积雪草苷高剂量组大鼠肺组织IL-6、TNF-α、IL-1β含量较模型组显著降低（P<0.05,P<0.01）,积雪草苷低剂量组TNF-α、IL-1β含量较模型组明显降低（P<0.05）。（3）HE染色观察显示,模型组大鼠肺泡结构破坏,成纤维细胞增生,伴有大量炎症细胞浸润;积雪草苷低、高剂量组和阳性对照组大鼠上述病变均有改善,炎症细胞浸润和肺泡萎陷减轻。结论:积雪草苷对平阳霉素诱导的大、小鼠肺纤维化具有保护作用,其机制可能与下调TGF-β₁mRNA表达、抑制炎症细胞因子激活有关。更多还原

【Abstract】 Objective: To investigate the protective effects of asiaticoside on bleomycin A₅-induced pulmonary fibrosis in mice and rats, and discuss the mechanism. Methods:（1）Experiment in mice: KM mice were randomly divided into the control group, model group, positive control group（prednisone acetate, 5 mg/kg）, asiaticoside low-dose（40 mg/kg） group and asiaticoside high-dose（80 mg/kg） group, 10 mice in each group. Except the control group, the mice in the other groups were treated with 5 mg/kg bleomycin A₅ by single tracheal injection to induce the pulmonary fibrosis model. On the next day of modeling, each group was treated with the corresponding drug intervention by intragastric administration for 28 days. After the last administration, the lung tissue was separated. The lung index was measured. The levels of interleukin（IL）-6, tumor necrosis factor-α（TNF-α） and IL-1β in lung tissue were detected by enzyme-linked immunosorbent assay（ELISA）. The mRNA expression of transforming growth factor-β₁（TGF-β₁） in the lung tissue was detected by PCR.（2）Experiment in rats: SD rats were randomly divided into the control group, model group, positive control group（prednisone acetate, 4 mg/kg）, asiaticoside low-dose（20 mg/kg） group and asiaticoside high-dose（40 mg/kg） group, 10 rats in each group. Except the control group, the rats in the other groups were treated with 5 mg/kg bleomycin A₅ by single tracheal injection to induce the pulmonary fibrosis model. On the next day of modeling, each group was treated with the corresponding drug intervention by intragastric administration for 28 days. After the last administration, the lung tissue was separated. The lung index was measured. After HE staining, the morphological changes of lung tissue were observed under light microscope. The levels of IL-6, TNF-α and IL-1β in lung tissue were detected by ELISA. The mRNA expression of TGF-β₁ in the lung tissue was detected by PCR. Results:（1）Experiment in mice: The lung index, the contents of IL-6, TNF-α, IL-1β and the expression of TGF-β₁ mRNA in the model group were significantly higher than those in the control group（P<0.01）. Compared with the model group, the lung index and the contents of IL-6, TNF-α and IL-1β in the positive control group, asiaticoside low-and high-dose groups were significantly reduced（P<0.05, P<0.01）, and the expression of TGF-β₁ mRNA in the asiaticoside low-and high-dose groups was significantly decreased（P<0.05）.（2）Experiment in rats: The lung index, the contents of IL-6, TNF-α, IL-1β and the expression of TGF-β₁ mRNA in the model group were significantly higher than those in the control group（P<0.01）. Compared with the model group, the lung index in the positive control group, asiaticoside low-dose group and high-dose group was significantly decreased（P<0.05, P<0.01）, and the expression of TGF-β₁ mRNA in lung tissue was decreased significantly（P<0.01）; the contents of IL-6, TNF-α and IL-1β in the positive control group and asiaticoside high-dose group were significantly lower than those in the model group（P<0.05, P<0.01）, and the contents of TNF-α and IL-1β in the asiaticoside low-dose group were significantly lower than those in the model group（P<0.05）.（3）HE staining showed that the alveolar structure of rats in the model group was destroyed, with fibroblasts proliferation and inflammatory cell infiltration. The above pathological changes were improved in the asiaticoside low-dose group and high-dose group and the positive control group, and the inflammatory cell infiltration and alveolar collapse were alleviated. Conclusion: Asiaticoside shows the protective effects on bleomycin A₅-induced pulmonary fibrosis in rats and mice, and its mechanism may be related to down-regulating the expression of TGF-β₁ mRNA and inhibiting the activation of inflammatory cytokines.更多还原