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CLC number: R563.9

On-line Access: 2015-01-05

Received: 2014-08-18

Revision Accepted: 2014-10-09

Crosschecked: 2014-12-24

Cited: 6

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Citations:  Bibtex RefMan EndNote GB/T7714


Jiang-hua CHEN


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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.1 P.52-61


Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

Author(s):  Xue Shao, Meng Li, Chong Luo, Ying-ying Wang, Ying-ying Lu, Shi Feng, Heng Li, Xia-bing Lang, Yu-cheng Wang, Chuan Lin, Xiu-jin Shen, Qin Zhou, Hong Jiang, Jiang-hua Chen

Affiliation(s):  Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   chenjianghua@zju.edu.cn

Key Words:  Paraquat, Pulmonary fibrosis, Rapamycin, Transforming growth factor-β, 1, α, -Smooth muscle actin, Methylprednisolone

Xue Shao, Meng Li, Chong Luo, Ying-ying Wang, Ying-ying Lu, Shi Feng, Heng Li, Xia-bing Lang, Yu-cheng Wang, Chuan Lin, Xiu-jin Shen, Qin Zhou, Hong Jiang, Jiang-hua Chen. Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice[J]. Journal of Zhejiang University Science B, 2015, 16(1): 52-61.

@article{title="Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice",
author="Xue Shao, Meng Li, Chong Luo, Ying-ying Wang, Ying-ying Lu, Shi Feng, Heng Li, Xia-bing Lang, Yu-cheng Wang, Chuan Lin, Xiu-jin Shen, Qin Zhou, Hong Jiang, Jiang-hua Chen",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice
%A Xue Shao
%A Meng Li
%A Chong Luo
%A Ying-ying Wang
%A Ying-ying Lu
%A Shi Feng
%A Heng Li
%A Xia-bing Lang
%A Yu-cheng Wang
%A Chuan Lin
%A Xiu-jin Shen
%A Qin Zhou
%A Hong Jiang
%A Jiang-hua Chen
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 1
%P 52-61
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400229

T1 - Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice
A1 - Xue Shao
A1 - Meng Li
A1 - Chong Luo
A1 - Ying-ying Wang
A1 - Ying-ying Lu
A1 - Shi Feng
A1 - Heng Li
A1 - Xia-bing Lang
A1 - Yu-cheng Wang
A1 - Chuan Lin
A1 - Xiu-jin Shen
A1 - Qin Zhou
A1 - Hong Jiang
A1 - Jiang-hua Chen
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 1
SP - 52
EP - 61
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400229

Background and aims: Ingestion of paraquat (PQ), a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. Methods: Male C57BL/6J mice were exposed to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally; test group). The test group was divided into four subgroups: a PQ group (PQ-exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically). The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E) and Masson 19;s trichrome stain for histopathological analysis. The hydroxyproline (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent assay (ELISA) kit. The expression of transforming growth factor-β;1 (TGF-β1) and ;1;-Smooth muscle actin (;1;-SMA) in lung tissues was detected by immunohistochemical staining and Western blotting. Results: A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that RAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen deposition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after RAPA treatment. Immunohistochemical staining and Western blotting showed that RAPA treatment significantly down-regulated the enhanced levels of TGF-β1 and ;1;-SMA in lung tissues caused by PQ exposure. However, RAPA treatment alone could not significantly ameliorate the lower survival rate and weight loss of treated mice. MP treatment enhanced the survival rate, but had no significant effects on attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-β1 and ;1;-SMA. Conclusions: This study demonstrates that RAPA treatment effectively suppresses PQ-induced alveolar collapse and collagen deposition in lung tissues through reducing the expression of TGF-β1 and ;1;-SMA. Thus, RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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