Protective effect of polydatin against burn-induced lung injury in rats.
BACKGROUND
Polydatin (PD) has anti-inflammatory and anti-apoptotic effects in ischemic-reperfusion injury. Moreover, inflammatory responses and apoptosis play a role in the development of burn-induced lung injuries. Based on these findings, in this study we investigated the hypothesis that PD can ameliorate lung injury induced by extensive burns via reduction of inflammation and apoptosis.


METHODS
Rats were subjected to 30% total body surface area burn injury followed by resuscitation. The treatment group received 45 mg/kg PD, and the burn group received the same amount of normal saline solution. No burn injury was inflicted in the sham group. Microvascular permeability, interstitial edema, neutrophil recruitment, and histopathological changes were detected by measuring Evans blue concentration, wet-to-dry lung weight ratio (W/D), myeloperoxidase (MPO) activity, and hematoxylin and eosin staining, respectively. To investigate the mechanism of action of PD, enzyme-linked immunosorbent assay, cell counting, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-triphosphate-digoxigenin nick end labeling (TUNEL) staining, fluorometric assay, and Western blot were used for assessing levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-1β, and IL-6), total number of cells, and concentration of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF), the number of apoptotic cells, caspase-3 activity, and apoptosis-related proteins including Bax and Bcl-xl, respectively.


RESULTS
Burn-injury rats exhibited significant lung injury characterized by the deterioration of histopathological characteristics, pulmonary microvascular hyperpermeability, and a high W/D, which were attenuated by PD (P = .007 for permeability, P = .004 for W/D). PD inhibited the burn-induced inflammatory response, as evidenced by the down-regulation of lung MPO activity (P = .008), total number of cells, PMN concentration in BALF, and the local and systemic levels of the pro-inflammatory cytokines examined. Moreover, PD treatment dramatically prevented burn-induced pulmonary cell apoptosis in lungs, as reflected by the decrease in the number of TUNEL-positive cells (P = .002) and changes in Bax, Bcl-xl, and caspase-3 activity (P = .03).


CONCLUSIONS
PD ameliorates burn-induced lung injury via its anti-inflammatory and anti-apoptotic effects, and PD treatment may therefore serve as a potential therapeutic target for the treatment of critical burn injuries.
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Tao
T
Li
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Shumin
S
Cai
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China. Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou, People's Republic of China.
Zhenhua
Z
Zeng
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Junli
J
Zhang
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China. Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
Youguang
Y
Gao
Department of Clinical Laboratory, Maternal and Child Health Hospital of Liuzhou, Liu Zhou, People's Republic of China.
Xingmin
X
Wang
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China. zhongqingchen.edu@gmail.com.
Zhongqing
Z
Chen
D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002056:Burns / Q000150:complications / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D009195:Peroxidase; D053148:Caspase 3; C058229:polydatin
apoptosis; extensive burn; inflammation; lung injury; permeability; polydatin