| 叶旭星,杨超,章义利,林军梅,陈燕萍,盛琳,王晓波.丹参酮ⅡA通过调节PINK1/Parkin通路改善COPD大鼠急性肺损伤的机制研究[J].浙江中西医结合杂志,2025,35(6): |
| 丹参酮ⅡA通过调节PINK1/Parkin通路改善COPD大鼠急性肺损伤的机制研究 |
| Mechanism of tanshinone IIA ameliorates acute lung injury in COPD rats by regulating the PINK1/Parkin pathway |
| 投稿时间：2024-11-06 修订日期：2025-02-17 |
| DOI： |
| 中文关键词: 大鼠 丹参酮ⅡA PINK1 Parkin COPD |
| 英文关键词:Rat Tanshinone IIA PINK1 Parkin COPD |
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| 中文摘要: |
| 摘要：目的 探讨丹参酮IIA通过调节同源性磷酸酶张力蛋白诱导的激酶1[phosphatase and tensin homologue（PTEN）-induced putative kinase 1，PINK1]/Parkin通路来改善慢性阻塞性肺疾病（COPD）引起的大鼠急性肺损伤作用机制。方法 将无特定病原体(SPF)?级雄性SD大鼠分为空白组、模型组和丹参酮IIA组，每组6只。除空白组外，其余两组通过香烟烟熏结合气管内注射脂多糖构建大鼠COPD模型。造模后丹参酮IIA组连续8周每日灌胃丹参酮IIA 10 mg/kg，空白组、模型组给予等量生理盐水灌胃。通过记录大鼠质量，检测肺功能，肺组织干湿重量比，肺通透性，肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β）、超氧化物歧化酶（SOD）、丙二醛（MDA）以及线粒体自噬相关蛋白PINK1、Parkin mRNA和蛋白的表达评估丹参酮IIA对COPD大鼠肺损伤的影响。结果 与空白组相比，模型组大鼠质量、PEF、FVC和FEV1/FVC明显下降（P<0.05），肺组织干湿重量比和肺通透性明显上升（P<0.05），丹参酮IIA组较模型组明显改善（P<0.05）。与空白组比较，模型组大鼠肺组织TNF-α[(51.17±1.74) ng/mg prot比(25.59±1.75) ng/mg prot，P<0.05]、IL-6表达[(370.51±23.96) ng/mg prot比(176.36±6.08) ng/mg prot，P<0.05]、IL-1β[(365.72±26.30) ng/mg prot比(170.90±16.01) ng/mg prot，P<0.05]表达升高，SOD活性[(139.81±18.87) U/mg prot比(177.00±24.02) U/mg prot，P<0.05]下降，相反MDA含量[(3.83±0.32) mmol/mgprot比(1.76±0.42) mmol/mgprot，P<0.05]上升，PINK1、Parkin mRNA[(1.80±0.16)比(0.97±0.08)，P<0.05；(1.87±0.06)比(0.99±0.09)，P<0.05]和蛋白[(1.83±0.15)比(0.99±0.10)，P<0.05；(1.87±0.08)比(0.97±0.11)，P<0.05]相对表达量升高。与模型组比较，丹参酮IIA组大鼠肺组织TNF-α[(41.19±5.39) ng/mg prot比(51.17±1.74) ng/mg prot，P<0.05]、IL-6[(334.08±21.86) ng/mg prot比(370.51±23.96) ng/mg prot，P<0.05]、IL-1β[(303.17±44.52) ng/mg prot比(365.72±26.30) ng/mg prot，P<0.05]表达降低，SOD活性[(178.01±14.72) U/mg prot比(139.81±18.87) U/mg prot，P<0.05]升高，MDA含量[(2.75±0.60) mmol/mg prot比(3.83±0.32) mmol/mg prot，P<0.05]降低，PINK1、Parkin mRNA[(1.38±0.13)比(1.80±0.16)，P<0.05；(1.51±0.11)比(1.87±0.06)，P<0.05]和蛋白[(1.50±0.16)比(1.83±0.15)，P<0.05；(1.59±0.18)比 (1.87±0.08)，P<0.05]相对表达量降低。结论 丹参酮IIA可显著缓解COPD大鼠肺损伤，其机制可能与降低炎症因子表达、抑制氧化应激、调节线粒体自噬PINK1/Parkin通路有关。 |
| 英文摘要: |
| Abstract: Objective To investigate tanshinone IIA ameliorates chronic obstructive pulmonary disease (COPD)-induced acute lung injury in rats by modulating the homologous phosphatase tensin-induced kinase 1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1, PINK1]/Parkin pathway Mechanism of action. Methods Specific pathogen free (SPF) grade male SD rats were divided into a blank group, a model group and a tanshinone IIA group, with 6 rats in each group. Except for the blank group, the rat COPD model was constructed by cigarette smoking combined with intratracheal injection of lipopolysaccharide in the remaining two groups. After modelling, the tanshinone IIA group was gavaged with tanshinone IIA 10 mg/kg daily for 8 consecutive weeks, and the blank and model groups were given equal amounts of saline gavage. The effects of tanshinone IIA on COPD were assessed by recording the mass of rats, detecting the lung function, wet and dry weight ratio of lung tissue, lung permeability, and the expression of tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), superoxide dismutase (SOD), malondialdehyde (MDA), as well as the expression of mitochondrial autophagy-related proteins, PINK1, and Parkin mRNA and protein. Effects of tanshinone IIA on lung injury in COPD rats.
ResultsCompared with the blank group, rats in the model group showed a significant decrease (P<0.05) in mass, PEF, FVC and FEV1/FVC, and a significant increase (P<0.05) in lung tissue wet and dry weight ratios and lung permeability, and a significant improvement (P<0.05) in the tanshinone IIA group compared with the model group. Compared with the blank group, lung tissue TNF-α [(51.17±1.74) ng/mg prot compared with (25.59±1.75) ng/mg prot, P<0.05], IL-6 expression [(370.51±23.96) ng/mg prot compared with (176.36±6.08) ng/mg prot, P< 0.05], elevated expression of IL-1β [(365.72±26.30) ng/mg prot vs. (170.90±16.01) ng/mg prot, P<0.05] and SOD activity [(139.81±18.87) U/mg prot vs. (177.00±24.02) U/mg prot, P<0.05 ] decreased, on the contrary MDA content [(3.83±0.32) mmol/mgprot than (1.76±0.42) mmol/mgprot, P<0.05] increased, and PINK1, Parkin mRNA [(1.80±0.16) than (0.97±0.08), P<0.05; (1.87±0.06) than ( 0.99±0.09), P<0.05] and protein [(1.83±0.15) over (0.99±0.10), P<0.05; (1.87±0.08) over (0.97±0.11), P<0.05] relative expression was elevated. Compared with the model group, the relative expression of TNF-α [(41.19±5.39) ng/mg prot vs. (51.17±1.74) ng/mg prot, P<0.05], IL-6 [(334.08±21.86) ng/mg prot vs. (370.51±23.96) ng/mg prot], IL-6 [(334.08±21.86) ng/mg prot vs. (370.51±23.96) ng/mg prot, P<0.05], IL-6 [(334.08±21.86) ng/mg prot vs. (370.51±23.96) ng/mg prot, P<0.05], and IL-6 [(370.51±23.96) ng/mg prot vs. P<0.05], IL-1β [(303.17±44.52) ng/mg prot vs. (365.72±26.30) ng/mg prot, P<0.05] expression was decreased and SOD activity [(178.01±14.72) U/mg prot vs. (139.81±18.87) U/mg prot, P< 0.05] was elevated, MDA content [(2.75±0.60) mmol/mg prot vs. (3.83±0.32) mmol/mg prot, P<0.05] was decreased, and PINK1, Parkin mRNA [(1.38±0.13) vs. (1.80±0.16), P<0.05; (1.51±0.11) vs. (1.87±0.06), P<0.05] and protein [(1.50±0.16) versus (1.83±0.15), P<0.05; (1.59±0.18) versus (1.87±0.08), P<0.05] relative expression was reduced. Conclusion Tanshinone IIA significantly alleviated lung injury in COPD rats, and the mechanism may be related to the reduction of inflammatory factor expression, inhibition of oxidative stress, and regulation of mitochondrial autophagy PINK1/Parkin pathway. |
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