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Objective To investigate the changes of Th1/Th2 cytokines and its relationship with lipopolysaccharide (LPS) in pretreatment of relieving nonalcoholic steatohepatitis (NASH).Methods The 24 male Wistar rats were randomly divided into 3 groups: normal control group, liver injury group and LPS pretreatment group. The rats were given normal diet in normal control group,high-sucrose and high-fat diet both in liver injury group and in LPS pretreatment group, and the rats in LPS pretreatment group were given hypodermic injection of LPS 0. 5 mg/kg every other day. The level of plasma endotoxin (ET), activity of alanine aminotransferase (ALT), content of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were determined. At the end of week 9, the rats were executed, and the liver tissue slices were prepared to investigate hepatic pathologic change by hematoxylin and eosin (HE) staining.Results The level of plasma ET was significantly higher in liver injury group than in normal control group. The level of plasma ALT and infiltrating lymphocytes in liver tissue were significantly lower in LPS pretreatment group than in liver injury group. The level of plasma TNF-α was significantly lower in LPS pretreatment group compared with liver injury group.In contrast, the level of plasma IL-10 was higher (P＜0. 05). Histology with HE staining showed that hepatocyte steatosis was obviously relieved with smaller lipid droplet in LPS pretreatment group than in liver injury group. Conclusions LPS pretreatment can alleviate high-sucrose and high-fat induced NASH. The disequilibrium of Th1/Th2 cytokines may be an important part of mechanism.
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<p><b>OBJECTIVE</b>To observe the effect of glycine on the expression of CD(14) mRNA and protein of hepatic tissue in the course of developing cirrhosis of rats.</p><p><b>METHODS</b>The cirrhotic model of Wistar rats was established by complex pathogens, who were respectively fed with control diets and control diets adding glycine (1g/d, giving by intragastric infusion) or 5% glycine containing diets at the same time. The rats were sacrificed at 2, 4, and 8 weeks, respectively. Hepatic tissues were collected to measure the expression of CD(14) mRNA and CD(14) protein by the reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis.</p><p><b>RESULTS</b>The expression of CD(14) mRNA and CD(14) protein in the hepatic tissue of fatty liver and cirrhotic rats fed with diets containing glycine was weaker than their control groups, and the expression of CD(14) mRNA and protein was the weakest in 8 weeks cirrhotic rats fed with the diets.</p><p><b>CONCLUSIONS</b>Glycine can markedly downregulate the expression of CD(14) mRNA and CD(14) protein in hepatic tissues of cirrhotic rats.</p>
Subject(s)
Animals , Male , Rats , Disease Models, Animal , Gene Expression , Glycine , Pharmacology , Lipopolysaccharide Receptors , Genetics , Liver Cirrhosis , Genetics , Metabolism , RNA, Messenger , Rats, Wistar , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
AIM: The goal of the present study was to evaluate the possibility about enterogenous endotoxemia in pathogenesis of hepatopulmonary syndrome. METHODS: The rat model of cirrhosis was prepared with compound factors. A small dose of lipopolysaccharide (LPS) was administered intraperitoneally once to aggravate endotoxemia of animal with cirrhosis. The normal rats injected with LPS or injected with LPS combined with glycine (LPS antagonist) were designed as controls. RESULTS: Hepatopulmonary syndrome of rats with cirrhosis had occurred in the end of eighth weeks. Pulmonary pathological changes of cirrhosis rats were exacerbated after administration of a given dose of LPS. Glycine sharply antagonized the biological effect of LPS in vivo and in vitro, inhibited the production of TNF-? by LPS and alleviated various pathological changes of hepatopulmonary syndrome. CONCLUSIONS: Enterogenous endotoxemia in cirrhosis rats might be an important mechanism in the development of hepatopulmonary syndrome. Endotoxin and its mediating effect by way of cytokines (TNF-?) may play a role in the pathogenesis of hepatopulmonary syndrome.
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AIM: To investigate the effects of nitric oxide (NO) on hepatic encephalopathy in cirrhotic rats induced by LPS. METHODS: The cirrhotic model of rats was established by complex pathogeny. Since the end of the 8 th week, the rats were intragastrically-infused with 0.9% salt, L-arginine(L-arg) and LNNA respectively for 2 weeks.The hepatic encephalopathy in cirrhotic rats were induced by 3 mg/kg LPS (ip) 4 hours before the rats were sacrificed. RESULTS: The normal behaviors and electroencephalograph were appeared in L-arg group. LNNA group showed hepatic encephalopathy. The content of NO-_2/NO-_3 of brain tissue was markedly higher in L-arg group than LNNA group(P
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AIM:To study the effect of intestinal endotoxemia(IETM) on hepatic energy metabolism in acute liver failure. METHODS:Intoxication by thioacetamide (TAA) was used to establish rat model of acute liver injury.Ketone body(acetoacetate and ?-hydroxybutyrate) in arterial blood and ATP content of hepatocellular mitochondria were determined by using enzymatic fluorimetric micromethod.Colectomy was adopted in observing the changes in plasma endotoxin content and serum alanine aminotransferase (ALT) activity. RESULTS:In the TAA group,plasma endotoxin content and serum ALT activity were all significantly higher than those in the control group(P
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AIM: To investigate the effect of LPS on phagocytosis of Kupffer cells in vitro. METHODS: Isolated Kupffer cells were treated with LPS in vitro . The phagocytosis, microfilament, microtubules and apoptosis of Kupffer cells were determined by the beads phagocytosis test, fluorescence staining, fluorometry and flow cytometric analysis. RESULTS: LPS enhances the phagocytosis, actin content, microtubules fluorescence density of Kupffer cells in vitro , while at a large dose or for a long time, it lessened the phagocytosis increasing or phagocytosis, inhibites the microfilament and microtubules expression, and induced apoptosis. CONCLUSION: LPS enhances the phagocytosis of Kupffer cells in vitro , but in large amount, it inhibites the phagocytosis of Kupffer cells, which is probably related to LPS -induced microfilament, microtubules expression changes and apoptosis in Kupffer cells.
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In this study, carbontetrachloride was administered orally to male Wistarrats at a dose of 2.5ml/kg body weight. The protective effects of RSM were comparedwith that of verapamil (a well-known calcium antagonist), and regitine (a vasodilator),to study the mechanisms of RSM action. The results showed that a significant correlation between CCl_4-induced liver tissuenecrosis and liver tissue calcium content(r=0.887, P
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AIM:To investigate the effect of lipopolysaccharides(LPS)preconditioning on CCl4-induced liver injury and the change of LPS signal transduction.METHODS:The male Wistar rats were divided randomly into liver-injury group,which were injected with CCl4 5 mL/kg first,three days later were injected 0.3 mL 40% CCl4 and 60% olive oil. Animals in LPS preconditioning group were injected with LPS 0.5 mg/kg before the day CCl4 was given. Rats received high fat diet were as liver injury group,and normal control group received normal diet. The lymphocytes infiltrated in the liver tissue were counted. The endotoxin and ALT level in rat plasma,TNF-? content and expressions of TLR4,p38,p-p38,I??,NF-?? in the rat livers were also determined.RESULTS:The lymphocytes in liver slice and ALT level of the plasma in LPS preconditioning group were lower significantly than those in the liver injury group,and the expressions of TLR4,p-p38,NF-?? in the liver were the same. In contrast,the expression of I?? was higher.CONCLUSION:LPS preconditioning relieves obviously CCl4-induced chronic liver injury. The mechanism may be associated with change of signal transduction of LPS,which results in decrease of pre-inflammatory cytokines.