| 姜爱雯,杜佩珊,褚明娟,等.白花前胡有效成分激活 PGC-1α/SIRT3信号通路降低慢性阻塞性肺疾病气道黏液高分泌的机制研究[J].安徽医药,2025,29(6):1120-1126. |
| 白花前胡有效成分激活 PGC-1α/SIRT3信号通路降低慢性阻塞性肺疾病气道黏液高分泌的机制研究 |
| Activation of the PGC-1α/SIRT3 signaling pathway by Baihua Qianhu active constituents: mechanism underlying reduced airway mucus hypersecretion in chronic obstructive pulmonary disease |
| |
| DOI：10.3969/j.issn.1009-6469.2025.06.011 |
| 中文关键词: 前胡 慢性阻塞性肺疾病 白花前胡丁素 气道黏液高分泌 气道炎症 PGC-1α/SIRT3信号通路 |
| 英文关键词: Hogfennel root Chronic obstructive pulmonary disease Baihua Qianhu Ding Su Airway mucus hypersecretion Airway inflammation PGC-1α/SIRT3 signaling pathway |
| 基金项目:张家口市 2022年市级科技计划自筹经费项目( 2221152D) |
|
| 摘要点击次数: 73 |
| 全文下载次数: 20 |
| 中文摘要: |
| 目的探究白花前胡有效成分通过过氧化物酶体增殖物激活受体 γ辅激活因子 1α(PGC-1α)/沉默信息调节因子 3(SIRT3)信号通路对慢性阻塞性肺疾病( COPD)大鼠气道黏液高分泌及炎症反应的影响机制。方法 2022年 9月至 2023年 5月，选取 SD雄性大鼠 80只作为研究对象，其中 10只用于建立白花前胡丁素( PD)在 SD大鼠体内血药浓度 -时间曲线，除去对照组( n=10)其余大鼠( n=60)均采用烟熏联合脂多糖法建立 COPD模型，采用随机数字表法分为 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(PGC-1α/SIRT3信号通路抑制剂)组( n=10)、中剂量 PD+SR-18292组( n=10)。统计对照组、 COPD组、低剂量 PD组、中剂量 PD组、高剂量 PD组五组大鼠干预治疗后脏器指数、弥漫性肺泡损伤标准(DAD)评分、肺部组织病理形态变化、主动脉血炎症因子［核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体 3(NLRP3)、白细胞介素( IL)-1β、IL-6、IL-8、肿瘤坏死因子 α(TNF-α)］、血管内皮细胞生长因子( VEGF)、氧化应激性因子［超氧化物歧化酶( SOD)、丙二醛］、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 PD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，然后缓慢消除，符合常规中药剂在机体内分解规律；与对照组大鼠相比， COPD模型的建立可以下调大鼠胸腺、脾脏指数、 SOD水平，上调 DAD评分、炎症因子( NLRP3、IL-1β、IL-6、IL-8、TNF-α)、 VEGF、丙二醛及核因子 κB(NF-κB)阳性占比( P<0.05)； PD的干预可以上调胸腺、脾脏指数、 SOD水平，下调 DAD评分、 NLRP3、IL-1β、IL-6、IL-8、TNF-α、VEGF、丙二醛及 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)。与对照组相比， COPD组大鼠肺部组织 PGC-1α/SIRT3信号通路关键蛋白 PGC-1α、SIRT3表达降低( 0.28±0.11、0.30±0.17比 0.65±0.26、0.68±0.20)(P<0.05)；与 COPD组相比，低、中、高剂量 PD的干预可以上调肺部组织内 PGC-1α、SIRT3蛋白表达( 0.40±0.22、0.48±0.30、0.57±0.28比 0.28±0.11，0.43±0.26、0.53±0.18、 0.60±0.21比 0.30±0.17)(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( 0.48±0.30、0.53±0.18比 0.65±0.26、0.68±0.20)(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( 0.57±0.28、0.60±0.21比 0.48±0.30、0.53±0.18)(P<0.05)。结论 PD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 COPD大鼠病理状态，改善其气道内黏液高分泌状态，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 To investigate the mechanism by which active components of Peucedanum praeruptorum Dunn regulate the peroxisome proliferator-activated receptor γ coactivator lα (PGC-1α)/silent informating regulator 3 (SIRT3) signaling pathway in chron-ic obstructive pulmonary disease (COPD) rats, with a focus on airway mucus hypersecretion and inflammatory responses. Methods From September 2022 to May 2023, 80 male SD rats were selected. Ten rats were used to establish the pharmacokinetic profile of Prae-ruptorin D (PD). The remaining 60 rats were divided into six groups: chronic obstructive pulmonary disease (COPD) model 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-1α/SIRT3 signaling pathway inhibitor)group (n=10), and medium-dose PD+SR-18292 group (n=10). The COPD model was established using a smokingcombined with lipopolysaccharide method. After intervention, organ index, diffuse alveolar damage (DAD) score, pathological changesin lung tissue, inflammatory factors (NLRP3, IL-1β, IL-6, IL-8 and TNF-α), angiogenesis factor (VEGF), oxidative stress factor (SOD, MDA), and levels of PGC-1α/SIRT3 signaling pathway proteins in lung tissue were analyzed.Results The blood concentration-time curve of Baihua Pembritin in SD rats indicated that the compound underwent initial metabolism within 2 hours, followed by gradualelimination, consistent with the metabolic pattern of traditional Chinese medicine in vivo. Compared to the Sham group, the COPD mod-el group exhibited significant downregulation of thymus and spleen indices and oxidative stress factor SOD levels, alongside upregulat-ed DAD scores, inflammatory factors (NLRP3, IL-1β, IL-6, IL-8, TNF-α), angiogenesis factor VEGF, oxidative stress factor MDA, and nuclear factor NF-κB (all P<0.05). PD intervention upregulated thymus and spleen indices and SOD levels while downregulating DAD scores, NLRP3, IL-1β, IL-6, IL-8, TNF-α, VEGF, MDA, and NF-κB. These effects became more pronounced with increasing PD doses, demonstrating a dose-dependent trend (P<0.05); In the PGC-1α/SIRT3 signaling pathway, COPD model rats showed reduced expres-sion of key proteins PGC-1α and SIRT3 (0.28±0.11 and 0.30±0.17 vs. Sham group: 0.65±0.26 and 0.68±0.20; P<0.05). Low-, medium-,and high-dose PD interventions upregulated PGC-1α (0.40±0.22, 0.48±0.30, 0.57±0.28 vs. model: 0.28±0.11) and SIRT3 (0.43±0.26, 0.53±0.18, 0.60±0.21 vs. model: 0.30±0.17) in lung tissue (P<0.05), with expression levels increasing dose-dependently. The PGC-1α/ SIRT3 inhibitor SR-18292 downregulated protein expression (0.48±0.30 and 0.53±0.18 vs. Sham: 0.65±0.26 and 0.68±0.20; P<0.05), while PD intervention reversed this effect, restoring PGC-1α (0.57±0.28) and SIRT3 (0.60±0.21) expression (P<0.05). Conclusions PD exhibits stable pharmacokinetics and enhances PGC-1α/SIRT3 signaling, thereby alleviating airway mucus hypersecretion and re-ducing inflammation and oxidative stress in COPD rats. These findings warrant further clinical investigation. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
