Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis.
OBJECTIVE
To investigate the effect of emodin on expression of claudin-4, claudin-5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate.


METHODS
Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) level were measured by enzyme-linked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin-4, claudin-5 and occludin in lung tissue samples was examined by immunohistology, quantitative real-time reverse transcription polymerase chain reaction and Western blotting analysis, respectively.


RESULTS
Pancreatitis-associated lung injury was characterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-alpha and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bronchial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin.


CONCLUSIONS
Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis.
Xia
Xian-Ming
XM
Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing 210002, Jiangsu Province, China. drxxming@gmail.com
Wang
Fang-Yu
FY
Wang
Zhen-Kai
ZK
Wan
Hai-Jun
HJ
Xu
Wen-An
WA
Lu
Heng
H
D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects* / Q000502:physiology; D062506:Claudin-4; D062507:Claudin-5; D004642:Emodin / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D011654:Pulmonary Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology
D062506:Claudin-4; D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D047428:Protein Kinase Inhibitors; D013656:Taurocholic Acid; D004642:Emodin