Effect of radix paeoniae rubra on expression of p38 MAPK/iNOS/HO-1 in rats with lipopolysaccharide-induced acute lung injury.
OBJECTIVE
To investigate the effect of radix paeoniae rubra (RPR) on expression of p38 mitogen activated protein kinase (MAPK)/iNOS/HO-1 in rats with lipopolysaccharide-induced acute lung injury and explore the molecular mechanism.


METHODS
Forty healthy male Wistar rats, weighing 200-250 g, aged 6-8 weeks (mean equal to 7 weeks), provided by the Experimental Center, Medical College, Wuhan University, Wuhan, China, were employed in this study. Under anesthesia with 7% chloraldurat (5 ml/kg body weight) through intraperitoneal injection, the trachea of the rat was exposed and an arterial puncture needle pricked into the trachea via cricothyroid membrane. Then they were randomly divided into five groups: 8 rats receiving 1 ml normal saline through the puncture needle (Group A), 8 receiving 1 ml lipopolysaccharide (LPS, 2.5 mg/kg, Group B), 8 receiving LPS and RPR (30 mg/kg, pumped through the femoral vein for 2 hours, Group C), 8 receiving RPR 2 hours before dripping LPS (Group D), and 8 receiving hemin (75 micromol/L through intraperitoneal injection) 18 hours before dripping LPS (Group E). After 6 hours of LPS dripping, blood samples were obtained through the carotid artery to perform blood gas analysis, then all the rats were exsanguinated to death and specimens of lung tissues were obtained. The pathomorphological changes of the lung tissues were observed. The expression of p38 MAPK/iNOS/HO-1, the neutrophil ratio, protein content in alveolar irrigating solution and malonaldehyde (MDA) content in the lung tissues were also detected.


RESULTS
Compared with Group A, the expression of p38 MAPK, iNOS and HO-1 markedly increased in Groups B, C, D, and E (P < 0.01). But in Groups C, D and E the expression of p38 MAPK and iNOS were significantly lower than that of Group B, while expression of HO-1 was obviously higher than that of Group B (P < 0.05). The protein content, the ratio of neutrophils in bronchoalveolar lavage fluid (BALF), the content of MDA and the activities of serum NO in Group B were significantly higher than those of Group A (P < 0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in Group B (P < 0.01). Compared with Group B, these indexes of lung injury were significantly lower while the levels of arterial bicarbonate and partial pressure of oxygen increased significantly in Groups C, D and E (P < 0.05 or P < 0.01). Under light microscope, the pathological changes induced by LPS were significantly attenuated by RPR and hemin.


CONCLUSIONS
The high expression of MAPK plays an important role in lipopolysaccharide-induced acute lung injury. Protective effect of RPR on lipopolysaccharide-induced acute lung injury may be related to the inhibition of the abnormal high expression of p38 MAPK/iNOS/HO-1.
Li-ying
Zhan
Z
Department of Anesthesiology, People's Hospital, Wuhan University, Wuhan 430060, China. zhlyyhb@yahoo.com.cn
Zhong-yuan
Xia
X
Fang
Xia
X
Bang-chang
Cheng
C
D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000032:analysis*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000032:analysis*; D029596:Paeonia; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis*
D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases