云药天龙竭分期干预对肺纤维化大鼠肺组织重构和肺功能的影响

doi:10.19803/j.1672-8629.20230506

摘要/Abstract

摘要： 目的观察天龙竭分期干预对肺纤维化大鼠肺组织重构及肺功能的影响,探讨其干预肺纤维化的作用机制。方法采用博来霉素法建立大鼠肺纤维化模型。90只大鼠随机分为9组：空白对照组,模型早期组,模型晚期组,天龙竭早期干预组,天龙竭晚期干预低、中、高剂量组（0.51、1.01、2.02 g·kg^-1·d^-1）,吡非尼酮早期干预组,吡非尼酮晚期干预组。早期干预组与晚期干预组分别于造模后第7天或第14天起灌胃相应药物,连续用药,观察大鼠的生存状态并于造模后第28天取材。以SABC技术检测CD31、CD34在肺组织中的蛋白表达,比色法检测肺组织中Hyp含量,并剥离肺脏计算肺系数,采用动物肺功能仪测定相关肺功能数值,并于腹主动脉取血进行血气分析检测。结果与模型组比较,天龙竭早期及晚期干预均可降低肺纤维化大鼠肺组织中CD31、CD34的蛋白表达水平（P<0.01,P<0.00 1）;早期干预与晚期干预中剂量组比较,存在显著差异（P<0.05）;晚期干预高、中剂量组与低剂量组比较,存在显著差异（P<0.05）。吡非尼酮早期及晚期干预均可降低肺纤维化大鼠肺组织中CD31、CD34蛋白表达水平（P<0.05）。天龙竭早期干预与吡非尼酮早期干预比较无显著性差异（P>0.05）,天龙竭晚期干预中剂量组与吡非尼酮晚期干预比较无显著性差异（P>0.05）。与模型组比较,各干预组羟脯氨酸含量降低（P<0.05, P<0.01）,天龙竭早期干预与吡非尼酮早期干预比较无显著性差异（P>0.05）,天龙竭晚期干预中剂量组与吡非尼酮晚期干预比较无显著性差异（P>0.05）。与模型组比较,天龙竭干预组肺质量及肺系数明显降低（P<0.05,P<0.01）。天龙竭各干预组与吡非尼酮组比较无显著差异（P>0.05）。与模型组比较,天龙竭干预组可升高FVC、FEV200、FEV200/FVC值（P<0.05,P<0.01,P<0.001）,降低FRC值（P<0.001）。结论天龙竭早期及晚期干预均可有效降低肺纤维化大鼠肺组织中CD31及CD34表达,早期干预更有意义;天龙竭可降低肺组织中Hyp含量,降低肺系数,改善肺通气功能,与吡非尼酮干预无明显差异。提示天龙竭可通过调节肺纤维化大鼠肺组织重构,从而阻抑肺纤维化进程。

关键词: 天龙竭, 肺纤维化, 血管重构, 肺系数, 肺功能, 博来霉素法, 吡非尼酮, 大鼠

Abstract: Objective To observe the effects of Tianlongjie (a Yunnan ethnic medicine) stage interventions on lung tissue remodeling and lung function of pulmonary fibrosis (PF) rats and explore the possible mechanism of Tianlongjie against pulmonary fibrosis. Methods A pulmonary fibrosis model of rats was established via intratracheal bleomycin infusion. Ninety male Wistar rats were randomized into nine groups: the control group(C), model early group(ME) and model late group(ML), Tianlongjie early intervention group at a medium dose(TEM), Tianlongjie late intervention group at a low dose(TLL), Tianlongjie late intervention group at a medium dose(TLM) , Tianlongjie late intervention group at a high dose(TLH)（0.51,1.01,2.02 g·kg^-1·d^-1）, pirfenidone early intervention group(PFDE) and pirfenidone late intervention group(PFDL). Rats in the early intervention group was given drugs from the 7^th day after modeling while the late intervention group was given drugs from the 14^th day. The survival of rats was observed and materials were selected on the 28^th day. The protein expressions of CD31 and CD34 in lung tissue were detected by SABC. The content of Hyp in lung tissue was determined with colorimetry. The lungs were stripped before the lung coefficient was calculated. Pulmonary function was measured by an animal pulmonary function instrument. Blood samples were taken from the abdominal aorta for blood gas analysis. Results Compared with the model control group, CD31 and CD34 protein expressions in lung tissue of PF rats were inhibited in early and late intervention with Tianlongjie groups (P<0.01, P<0.001), and there was significant difference between TEM and TLM (P<0.05). Compared with TLL, TLM and TLH were more effective (P<0.05). Early and late intervention with pirfenidone inhibited CD31 and CD34 protein expressions in lung tissue of PF rats (P<0.01). There was no statistically significant difference between TEM and PFDE(P>0.05), and the same was true of TLM and PFDL. Compared with the model control group, the level of Hyp in lung tissue of PF rats decreased in each of the intervention groups (P<0.05,P<0.01). There was no statistically significant difference between TEM and PFDE(P>0.05), as in the case of TLM and PFDL. Compared with the model control group, intervention with Tianlongjie reduced lung weight and lung coefficients (P<0.05, P<0.01). There was no significant difference between Tianlongjie intervention and pirfenidone intervention (P>0.05). Compared with the model control group, intervention with Tianlongjie increased levels of FVC, FEV200 and FEV200/FVC (P<0.05, P<0.01, P<0.001), but decreased FRC levels(P<0.001). Conclusion Early and late intervention with Tianlongjie can effectively inhibit CD31 and CD34 protein expressions, and early intervention is more effective. Intervention with Tianlongjie can decrease Hyp contents in lung tissue of PF rats before reducing the lung coefficient, improve lung ventilation function, but there is no significant difference between Tianlongjie and pirfenidone, indicating that Tianlongjie could effectively regulate lung tissue remodeling of PF rats and inhibit the progress of pulmonary fibrosis.

Key words: Tianlongjie, pulmonary fibrosis, vascular remodeling, lung coefficient, lung function, bleomycin infusion, pirfenidone, rats

中图分类号:

R974

陈冰, 袁德政, 付义. 云药天龙竭分期干预对肺纤维化大鼠肺组织重构和肺功能的影响[J]. 中国药物警戒, 2024, 21(5): 540-546.

CHEN Bing, YUAN Dezheng, FU Yi. Effect of Tianlongjie stage interventions on lung tissue remodeling and lung function of pulmonary fibrosis rats[J]. Chinese Journal of Pharmacovigilance, 2024, 21(5): 540-546.

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