| 姜爱雯.白花前胡有效成分调控PGC-1α/SIRT3信号通路对慢阻肺气道粘液高分泌的机制研究[J].安徽医药,待发表. |
| 白花前胡有效成分调控PGC-1α/SIRT3信号通路对慢阻肺气道粘液高分泌的机制研究 |
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| 投稿时间：2023-09-27 录用日期：2023-11-13 |
| DOI： |
| 中文关键词: 慢性阻塞性肺部病变 白花前胡丁素 气道粘液高分泌 气道炎症 PGC-1α/SIRT3信号通路 |
| 英文关键词: |
| 基金项目:张家口市2022年市级科技计划自筹项目（2221152D） |
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| 摘要点击次数: 82 |
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| 中文摘要: |
| 目的：探究白花前胡有效成分通过PGC-1α/SIRT3信号通路对慢阻肺大鼠气道粘液高分泌及炎症反应的影响机制。方法：选取SD大鼠作为研究对象除去空白对照组（Sham组,n=20），其余大鼠均采用烟熏联合脂多糖法构建慢性阻塞性肺部疾病（chronic obstructive pulmonary disease，COPD）模型；选取部分Sham组大鼠（n=10），基于高效液相色谱法建立白花前胡丁素（Peucedanum praeruotorum Dunn,PD）在SD大鼠体内血药浓度-时间曲线。构建Sham组（n=10）、COPD组（n=10）、低剂量PD组（n=10）、中剂量PD组（n=10）、高剂量PD组（n=10）、SR-18292组（PGC-1α/SIRT3信号通路抑制剂，n=10）、中剂量PD+SR-18292组（n=10）；统计Sham组、COPD组、低剂量PD组（n=10）、中剂量PD组（n=10）、高剂量PD组（n=10）五组大鼠干预治疗后脏器指数、弥漫性肺泡损伤标准（Standard for diffuse alveolar，DAD）评分、肺部组织病理形态变化、主动脉血炎性因子（NLRP3、IL-1β、IL-6、IL-8、TNF-α）、血管新生因子（VEGF）、氧化应激性因子（SOD、MDA）、肺部组织PGC-1α/SIRT3信号通路关键因子（PGC-1α、SIRT3）水平；统计COPD组、中剂量PD组、SR-18292组（PGC-1α/SIRT3信号通路抑制剂）、中剂量PD+SR-18292组四组大鼠肺部组织PGC-1α/SIRT3信号通路关键因子（PGC-1α、SIRT3）水平。结果：白花前胡丁素在SD大鼠内血药浓度-时间曲线趋势规律，其血药浓度在2h内完成基本代谢，然后缓慢的消除，符合常规中药剂在机体内分解规律；与Sham组大鼠相比，COPD模型的建立可以下调大鼠胸腺、脾脏指数、氧化应激性因子SOD水平，上调DAD评分、炎性因子（NLRP3、IL-1β、IL-6、IL-8、TNF-α）、血管新生因子（VEGF）、氧化应激性因子MDA及NF-κB阳性占比（P<0.05）；PD的干预可以上调胸腺、脾脏指数、氧化应激性因子SOD水平，下调DAD评分、NLRP3、IL-1β、IL-6、IL-8、TNF-α、VEGF、MDA及NF-κB阳性占比，随着PD干预剂量的提升，上述趋势逐渐明显，体现出剂量依赖性（P<0.05）。与Sham组大鼠相比，COPD模型建立后，大鼠肺部组织PGC-1α/SIRT3信号通路关键蛋白PGC-1α、SIRT3表达降低（P<0.05）；PD的干预可以上调肺部组织内PGC-1α、SIRT3蛋白表达（P<0.05），且随着PD干预剂量的提升，肺部组织内PGC-1α、SIRT3蛋白表达持续提升，体现出剂量依赖性（P<0.05）；PGC-1α/SIRT3信号通路抑制剂SR-18292干预可以下调COPD组大鼠肺组织内PGC-1α、SIRT3蛋白表达（P<0.05）；PD干预可以逆转SR-18292组大鼠表达趋势，再次上调肺部组织内PGC-1α、SIRT3蛋白表达（P<0.05）。结论：白花前胡丁素在大鼠体内药代动力学稳定，通过提升PGC-1α/SIRT3信号通路活性来抑制慢阻肺大鼠病理状态，改善其气道内粘液高分泌状态，降低气道炎症、氧化应激损伤程度，值得临床进一步研究。 |
| 英文摘要: |
| Objective: Exploring the effective ingredients of Baihua Qianhu through PGC-1 α/ The mechanism of the influence of SIRT3 signaling pathway on airway mucus hypersecretion and inflammatory response in rats with chronic obstructive pulmonary disease.Method: SD rats were selected as the study subjects, except for the blank control group (Sham group, n=20). All other rats were used to construct a chronic obstructive pulmonary disease (COPD) model using smoking combined with lipopolysaccharide method; Select a portion of Sham group rats (n=10) and establish a plasma concentration time curve of Peucedanum praeruotorum Dunn (PD) in SD rats using high-performance liquid chromatography. Construct Sham group (n=10), COPD group (n=10), low dose PD group (n=10), medium dose PD group (n=10), high dose PD group (n=10), SR-18292 group (PGC-1 α/ SIRT3 signaling pathway inhibitor (n=10), medium dose PD+SR-18292 group (n=10); Statistical analysis of organ index, Standard for diffuse alveolar injury (DAD) score, pathological changes in lung tissue, inflammatory factors（NLRP3 and IL-1β、IL-6, IL-8, TNF-α）、 Angiogenesis factor (VEGF), oxidative stress factor (SOD, MDA), lung tissue PGC-1 α/ SIRT3 signaling pathway key factor (PGC-1 α、SIRT3) level in aortic blood after intervention treatment in five groups of rats: Sham group, COPD group, low-dose PD group,medium dose PD group, and high-dose PD group; Statistical analysis of COPD group, medium dose PD group, SR-18292 group PGC-1α/SIRT3 signaling pathway inhibitor, medium dose PD+SR-18292 group of rat lung tissue PGC-1α/SIRT3 signaling pathway key factor (PGC-1α、SIRT3) horizontal.Result: The trend of the blood concentration time curve of Baihua Pembritin in SD rats showed that its blood concentration completed basic metabolism within 2 hours and then slowly eliminated, which is consistent with the decomposition law of conventional Chinese medicine in the body; Compared with the Sham group rats, the establishment of a COPD model can downregulate the thymus and spleen indices, oxidative stress factor SOD levels, and upregulate the DAD score and inflammatory factors (NLRP3, IL-1β、IL-6、IL-8、TNF- α、Angiogenesis factor (VEGF), oxidative stress factor MDA, and NF-κB) in rats positive proportion (P<0.05); Intervention with PD can upregulate thymus and spleen indices, oxidative stress factor SOD levels, and downregulate DAD scores, NLRP3, and IL-1 β、IL-6, IL-8, TNF-α、VEGF, MDA, and NF-κB, The proportion of positive cases gradually became apparent with the increase of PD intervention dose, indicating a dose-dependent (P<0.05) trend. Compared with the Sham group rats, after the establishment of the COPD model, the lung tissue PGC-1 of the rats α/ SIRT3 signaling pathway key protein PGC-1α、The expression of SIRT3 decreased (P<0.05); Intervention with PD can upregulate PGC-1α、SIRT3 tissue protein expression in lung (P<0.05), and with the increase of PD intervention dose, PGC-1α in lung tissue、The expression of SIRT3 protein continued to increase in a dose-dependent manner (P<0.05); PGC-1α/Intervention with SIRT3 signaling pathway inhibitor SR-18292 can downregulate PGC-1 α、SIRT3 protein expression in lung tissue of COPD rats (P<0.05); PD intervention can reverse the expression trend of SR-18292 group rats and upregulate PGC-1α、SIRT3 protein expression in lung tissue again (P<0.05).Conclusion: The pharmacokinetics of Baihua Pembritin in rats is stable, and it can enhance PGC-1α/ SIRT3 levels. The activity of signaling pathway can inhibit the pathological state of chronic obstructive pulmonary disease rats, improve their airway mucus hypersecretion state, reduce airway inflammation and oxidative stress damage, and is worthy of further clinical research. |
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