[Effect of mastoparan-1 on lipopolysaccharide-induced acute hepatic injury in mice].
OBJECTIVE
To observe the effect of mastoparan-1 (MP-1) on lipopolysaccharide (LPS)-induced acute hepatic injury in mice and probe into its possible mechanism.


METHODS
One hundred and four BALB/c mice were randomly divided into healthy control group (n = 8, without treatment, HC), LPS group (n = 48, with injection of LPS 5 mg/kg via tail vein), and MP-1 group (n = 48, with injection of LPS 5 mg/kg and MP-1 3 mg/kg via tail vein). Mice in LPS group and MP-1 group were sacrificed at 2nd, 6th, 12th, 24th, 48th and 72nd post injection hour (PIH), 8 mice at each time point in each group. Blood samples were collected for determination of plasma levels of LPS by kinetic turbidimetric limulus test, TNF-alpha and IL-6 by ELISA, serum levels of ALT and AST by automatic biochemistry analyzer respectively. Hepatic tissue samples were collected for determination of TLR4, TNF-alpha and IL-6 mRNA by real-time fluorescent quantitation reverse transcription polymerase chain reaction, along with the observation of pathological changes in hepatic tissue at each time point. Above-mentioned examinations were also performed in HC group.


RESULTS
Compared with those of HC group, plasma levels of LPS and TNF-alpha in LPS group significantly increased at 2nd PIH (18,320.50 +/- 2782.50 EU/mL and 988 +/- 130 ng/L, respectively), then decreased gradually to 1.80 +/- 0.80 EU/mL and 150 +/- 44 ng/L at 72nd PIH, which was close to those of HC group. The values of IL-6, ALT and AST peaked at 12th PIH, which declined to the levels close to those of HC group at 72nd PIH. Meanwhile, the expressions of TLR4, TNF-alpha and IL-6 mRNA in liver were remarkably up-regulated after injection, and the pathological changes in hepatic tissue pronounced significantly at 12th, 24th and 48th PIH. Compared with those of LPS group, the levels of LPS, cytokines, ALT and AST decreased in MP-1 group in different degrees after injection (P < 0.05 or P < 0.01), genes expression (P < 0.05 or P < 0.01) and pathological changes was respectively suppressed and alleviated in hepatic tissue.


CONCLUSIONS
MP-1 can alleviate LPS-induced acute hepatic injury in mice, which may be associated with its neutralization of LPS and attenuation of synthesis and release of inflammatory mediators.
Guo
Yi-bin
YB
Institute of Burns and Plastic Surgery of Nanjing Military Area Command, the 175th Hospital of PLA, Zhangzhou 363000, China.
Zheng
Qing-yi
QY
Chen
Jin-he
JH
Cai
Shao-fu
SF
Cao
Hong-wei
HW
Zheng
Jiang
J
Xiao
Guang-xia
GX
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004731:Endotoxins / Q000009:adverse effects; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D014862:Wasp Venoms / Q000494:pharmacology*
D004731:Endotoxins; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan