ABSTRACT
The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.
Subject(s)
Animals , Male , Mice , Cytochrome P-450 CYP2E1/pharmacology , Liver , Liver Diseases, Alcoholic/pathology , NF-kappa B/metabolism , Plant Extracts/pharmacology , Polysaccharides/pharmacology , WolfiporiaABSTRACT
<p><b>OBJECTIVE</b>To observe changes of plasma polypeptide hormone levels in rats with gastric ulcer after exposure to intense noise, and to discuss their mechanism.</p><p><b>METHODS</b>80 Wistar rats were used in the study. Plasma levels of rat gastrin (GAS), motilin (MTL), osteocalcin (BGP), substance P (SP), neurotensin (NT) and somatostatin (SS) in rats were measured by radioimmunoassay.</p><p><b>RESULTS</b>(1) In non-noise-exposure but with gastric ulcer group, the plasma MTL [(160.70 +/- 40.34) pg/ml] and BGP [(27.63 +/- 13.13) pg/ml] levels on 10 d after gastric ulcer model operation were remarkably higher than those in control group [(89.21 +/- 49.94) pg/ml, (9.10 +/- 1.38) pg/ml respectively] (P < 0.05 and P < 0.01), while the GAS level was remarkably descended [(107.00 +/- 21.75) vs (158.48 +/- 20.92) pg/ml] (P < 0.01). (2) In noise-exposure but without gastric ulcer group, the plasma MTL [(312.80 +/- 207.42) pg/ml] and BGP [(17.76 +/- 12.33) pg/ml] levels on 10 d were also significantly increased as compared with the control group (P < 0.01 and P < 0.05 respectively), while the GAS levels didn't change. (3) In noise-exposure + gastric ulcer group, the areas of gastric ulcer on 10 d and 40 d after noise and operation [(15.33 +/- 7.26) and (15.11 +/- 12.45) mm(2) respectively] were significantly larger than those of the control [(8.22 +/- 6.66), (3.67 +/- 9.90) mm(2)] (P < 0.05). The plasma MTL levels on 10 d and 40 d [(244.44 +/- 68.11) and (191.20 +/- 60.50) pg/ml respectively] were higher than those in control group [(160.70 +/- 40.34) and (93.10 +/- 52.90) pg/ml respectively] (P < 0.01).</p><p><b>CONCLUSION</b>Intense noise exposure may make the rat gastric ulcer worsened and induce negative effect on healing of it. The gastrointestinal endocrine would be disturbed by combined effect of intense noise exposure with gastric ulcer in rats.</p>