PPARγ激活剂对博莱霉素诱导小鼠肺纤维化的改善作用

李星; 朱振华; 吴仲敏; 董亮; 叶斌; 蔡荷飞

doi:10.16766/j.cnki.issn.1674-4152.002084

PPARγ激活剂对博莱霉素诱导小鼠肺纤维化的改善作用

doi: 10.16766/j.cnki.issn.1674-4152.002084

李星¹,
朱振华^1, ,,
吴仲敏²,
董亮³,
叶斌¹,
蔡荷飞¹

1.
台州市中心医院(台州学院附属医院)儿内科，浙江台州 318000
2.
台州学院医学院，浙江台州 318000
3.
台州市中心医院(台州学院附属医院)重症医学科，浙江台州 318000

基金项目:

国家自然科学基金项目 82072146

浙江省科技计划项目 2018C37108

详细信息

通讯作者:
朱振华，E-mail：zhuzh@tzzxyy.com

中图分类号: R563.13 R-332
计量
- 文章访问数: 316
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- PDF下载量: 5
- 被引次数: 0
出版历程
- 收稿日期: 2020-09-29
- 网络出版日期: 2022-02-15

Improved effect of PPARγ activator on bleomycin-induced pulmonary fibrosis in mice

1.
Department of Pediatrics, Taizhou Central Hospital (Affiliated Hospital of Taizhou University), Taizhou, Zhejiang 318000, China

摘要

摘要: 目的探讨过氧化物酶增殖激活受体γ(PPARγ)激活剂对博莱霉素诱导的小鼠肺纤维化的改善作用及相关机制。方法将36只BALB/c小鼠采用随机数字表法分成对照组、模型组和PPARγ激活组，每组12只。除对照组外，其余2组小鼠气管内注射博莱霉素5 mg/kg诱导肺纤维化模型。24 h后，PPARγ激活组小鼠口服灌胃100 mg/kg剂量的罗格列酮溶液。计算肺系数；ELISA法测定肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、羟脯氨酸(HYP)和转化生长因子-β1(TGF-β1)的含量；HE和Masson染色观察小鼠肺组织病理变化；Western blotting法检测肺组织PPARγ、PPARγ共激活因子α(PGC-1α)、核因子类胡萝卜素2相关因子(Nrf2)蛋白含量。结果模型组小鼠肺系数、肺组织Ashcroft评分及HYP、TGF-β1、MDA水平均显著高于对照组和PPARγ激活组(均P < 0.05)。模型组肺组织中SOD、GPx水平显著低于对照组和PPARγ激活组(均P < 0.05)。与模型组相比，PPARγ激活组小鼠肺组织PPARγ、PGC-1α、Nrf2蛋白表达量显著升高(均P < 0.05)。结论 PPARγ激活剂可抑制博莱霉素诱导的小鼠肺纤维化过程，可能与减轻炎症反应和氧化应激有关。
- 过氧化物酶增殖激活受体-γ /
- 博莱霉素 /
- 肺纤维化 /
- 炎症反应 /
- 氧化应激
Abstract: Objective To explore the effect of peroxisome proliferator-activated receptor-γ (PPARγ) activator on bleomycin-induced pulmonary fibrosis in mice and its related mechanisms. Methods Thirty-six BALB/c mice were randomly divided into control group, model group and PPARγ-activated group, 12 mice in each group. Except for the control group, the other groups of mice were injected intratracheally with 5 mg/kg bleomycin to induce pulmonary fibrosis. After 24 h, the mice in the PPARγ-activated group were orally administered with 100 mg/kg rosiglitazone solution. The lung coefficient was calculated. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1) in lung tissue were detected by ELISA. HE and masson staining were used to observe the pathological changes of lung tissue. The contents of PPARγ, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and nuclear factor erythroid-2-related factor (Nrf2) protein in lung tissue were detected by western blot. Results The lung coefficient, Ashcroft score of lung tissue, and the levels of HYP, TGF-β1 and MDA in the model group were significantly higher than those in the control group and PPARγ-activated group (all P < 0.05). The levels of SOD and GPx in the lung tissues of the model group were significantly lower than those of the control group and PPARγ-activated group (all P < 0.05). Compared with the model group, the expression of PPARγ, PGC-1α, and Nrf2 proteins in the lung tissue of rats in the PPARγ activation group increased significantly (all P < 0.05). Conclusion PPARγ activator can inhibit bleomycin-induced lung fibrosis in mice, which may be related to reducing inflammation and oxidative stress.
- Peroxisome proliferator-activated receptor-γ /
- Bleomycin /
- Pulmonary fibrosis /
- Inflammatory response /
- Oxidative stress

HTML全文

图 1 肺组织HE染色结果(×100)

注：A为对照组；B为模型组；C为PPARγ激活组。

下载: 全尺寸图片幻灯片

图 2 肺组织Masson染色结果(×200)

注：A为对照组；B为模型组；C为PPARγ激活组。

下载: 全尺寸图片幻灯片

图 3 各组小鼠肺组织WB检测结果

注：A为对照组；B为模型组；C为PPARγ激活组。

下载: 全尺寸图片幻灯片

表 1 3组小鼠肺组织HYP、TGF-β1水平比较(x±s, μg/mL)

组别	只数	HYP	TGF-β1
对照组	12	1.86±0.32	1.07±0.29
模型组	12	5.57±0.59^a	8.49±0.93^a
PPARγ激活组	12	3.83±0.46^b	3.26±0.67^b
F值		156.114	311.916
P值		< 0.001	< 0.001
注：与对照组比较，^aP < 0.05；与模型组比较，^bP＜0.05。

下载: 导出CSV

表 2 3组小鼠肺组织MDA、SOD、GPx水平比较(x±s)

组别	只数	MDA(nmol/mg)	SOD(U/mg)	GPx(U/mg)
对照组	12	8.45±0.79	12.86±1.08	84.59±11.37
模型组	12	26.71±1.53^a	4.29±0.46^a	22.16±6.49^a
PPARγ激活组	12	11.53±1.06^b	9.37±0.75^b	72.82±8.27^b
F值		701.152	287.120	137.672
P值		< 0.001	< 0.001	< 0.001
注：与对照组比较，^aP < 0.05；与模型组比较，^bP＜0.05。

下载: 导出CSV

表 3 3组小鼠肺组织PPARγ、PGC-1α、Nrf2蛋白相对表达量比较(x±s)

组别	只数	PPARγ	PGC-1α	Nrf2
对照组	12	0.94±0.18	0.79±0.15	0.97±0.14
模型组	12	0.34±0.09^a	0.18±0.08^a	0.38±0.07^a
PPARγ激活组	12	0.89±0.11^b	0.59±0.12^b	0.89±0.09^b
F值		63.213	66.998	94.264
P值		< 0.001	< 0.001	< 0.001
注：与对照组比较，^aP < 0.05；与模型组比较，^bP＜0.05。

下载: 导出CSV

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