Retinoic acid promotes the endogenous repair of lung stem-progenitor cells in combined with simvastatin after acute lung injury: a stereological analysisReport as inadecuate

Retinoic acid promotes the endogenous repair of lung stem-progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis - Download this document for free, or read online. Document in PDF available to download.

Respiratory Research

, 16:140

First Online: 11 November 2015Received: 06 February 2015Accepted: 03 November 2015


BackgroundThe treatment of acute respiratory distress syndrome ARDS, most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem-progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid RA plus simvastatin SS with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism.

Materials and methodsThe experimental Sprague–Dawley rats were divided randomly into normal control control, sham operated sham, ARDS, ARDS + vehicle and ARDS + RA + SS groups. ARDS was reproduced through hemorrhagic shock-resuscitation shock and subsequent intratracheal LPS 4.5 mg-kg, Escherichia coli serotype O55: B5 injection. The rats were treated by intragastric administration of RA 2 mg-kg-day and SS 2 mg-kg-day for 5 days in the ARDS + RA + SS group. Seven days after the first RA-SS injection, a right lower lobe of lung was sampled for histological analysis concerning systemic uniform random sampling method. Immunohistochemistry of inflation-fixed lungs for alveolar type 1 AT1, alveolar type 2 AT2 and Clara cells was measured by AQP5, Pro-SPC and CCSP staining respectively. The alveolar cell proliferation and apoptosis were analyzed with Ki67 staining and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling TUNEL method. Meanwhile, the alveolar cell numerical and surface density alveolar cells, AT1, AT2, Clara, proliferating and apoptotic cells were evaluated by stereology.

ResultsRA-SS compound exerted anti-inflammatory and pro-repairing effects on respiratory tracts in ARDS induced by hemorrhagic-endotoxin shock. The numerical density and surface density of alveolar cells, AT1 cell fraction, and numerical density of AT2 and Clara cells were significantly increased after treatment with RA-SS compound in ARDS. Concurrently, the Ki67+ alveolar cells were obviously increased while the TUNEL+ alveolar cells were reduced, which was correlated with the attenuation of inflammatory injury and functional repair in injured lung tissues.

ConclusionsOur data convincingly indicated that the prophylactic and therapeutic treatment of RA plus SS had obvious beneficial effect on the remodeling-regeneration of injured pulmonary tissues, suggesting that the underlying mechanisms are related to the re-balance between regeneration and apoptosis in lung stem-progenitor cells.

Keywordsstem-progenitor cells retinoic acid simvastatin apoptosis regeneration trauma and injury AbbreviationsARDSAcute respiratory distress syndrome

ATRAAll-trans retinoic acid

RARetinoic acid

AT1Alveolar type 1

AT2Alveolar type 1

BPBlood pressure

FABP5Fatty acid binding protein 5

HEhematoxylin and eosin

HRHemorrhagic shock-resuscitation

HMG-CoA3-hydroxy-3-methylglutaryl coenzyme A

LmLiner intercept

PBSPhosphate-buffered saline


TUNELTerminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling

UIRUniform isotropic random

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Author: Ce Yang - Xuetao Yang - Juan Du - Haiyan Wang - Haisheng Li - Ling Zeng - Wei Gu - Jianxin Jiang


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