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Objectives To explore the relativity between Alzheimer ’ s disease ( AD)-like lesions and metabolic syndrome models induced by high-sugar high-fat diet in rats.Methods Forty-eight Sprague Dawley rats were randomly divided into 2 groups.The control group (fed with normal diet, 12 rats) and high sugar and high fat group (fed with high-sucrose and high-fat diet, 12 rats) continuously for 12 months.At the end of 6, 9 and 12 months of the experiment , we observed the animal body weight and visceral fat weight .The blood lipid levels , blood glucose and MS-related biochemical parameters were determined . The brain tissues were examined by histopathology . The characteristic AD molecules hippocampus Aβand Tau were detected using ELISA and Western blotting to confirm the presence of AD lesions in the brain.Results Compared with the normal control group , the body weight and visceral fat weight of the rats in the high-sugar high-fat groups were significantly increased; the levels of TG , FPG, LDL, HOMA-IR and hippocampus Aβ,phosphorylated Tau (p-Tau) were higher, but the level of HDL was decreased (P<0.05 for all).The histopathological examination revealed inflammatory cell infiltration in the brain tissues .Conclusions Characteristic AD-like lesions may occur and accompany the rat models of metabolic syndrome , induced by high-sugar high-fat diet, and provide a new idea for the construction of Alzheimer ’ s disease animal models .
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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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Objective To investigate the effects of Shuangligan and Glycine on Thl/Th2 balancing on severe acute pancreatitis ( SAP) in rats. Methods Thirty-two Wistar rats weighing (260 ± 20) g were randomly divided into sham operation (SO) group, SAP group, SAP + Slg (with the treatment by Shuangligan) group and SAP + Gly (with the treatment by Glycine ) group. Each group included 8 rats, which accepted different treatment according to the experimental design. Changes of plasma level of endotoxin ( ET) and serum amylase (AMY) and the effects of Shuangligan and Glycine on Thl/Th2 ratio at the 24th hour after operation were observed respectively. Results The plasma endotoxin (ET) level ( (0. 67 ±0. 11) EU/ml),proinflammatory cytokine (INF-γ:(8.43 ± 0.86) ng/L, IL-12: (8.26 ± 1.97) ng/L) and Thl/Th2 ratio (0.36 ± 0.07) in SAP group were significantly higher than those in SO group( ET: (0. 44 ±0.07) EU/ml, INF-γ: (3. 80 ±0. 55) ng/L, IL-12: (3. 34 ± 1. 34)ng/L,Thl/Th2 ratio (0. 24 ±0. 05) ) (P <0. 05). Compared with SAP group, SAP + Slg and SAP + Gly group had remarkably decreased plasma ET level ( (0. 57 ± 0. 08,0. 52 ± 0. 04) EU/ml) (P < 0. 05) and the Thl/Th2 ratio reached equilibrium ( SAP + Slg group; (0. 29 ± 0. 04 ), SAP + Gly group: (0. 25 ± 0. 06 )) . Conclusions In the earlier stage of SAP, the rising plasma ET level may cause the overreaction of the cell mediated immune response, which leads to the aggravated damages in tissue cells. Our data indicates that Shuangligan and Glycine can restrain the formation of intestinal endotoxemia and alleviate or prevent the tissue injuries.
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AIM: To investigate the expression, distribution and significance of nuclear factor κB (NF-κB) in experimental hepatic fibrosis.METHODS: Wistar rats were randomly divided into normal control group, hepatic fibrisis model group and the pyrrolidine-1-dithiocarboxylic acid ammonium sail (PDTC) group. The PDTC group was treated with subcutaneous injection of carboan tetrachloride, and treated with PDTC by oral administration. The content of hydroxyproline was measured. Endotoxin was determined with a Limulus amebocyte lysate test kit. The alanine aminotransferase (ALT) in plasma was measured by laishi method. The content of malondialdehyde (MDA) in liver tissue was detected by means of TBA method. The expression of NF-κB was determined by immunohistochemistry. The expression of connective tissue growth factor (CTGF) was measured by Western blotting.RESULTS: In control group, just a small amount of NF-κB p65 was expressed in the cytoplasm of a few hepatocytes around central veins. In model group, the positive staining of NF-κB p65 was expressed in cytoplasm and nucleus, mainly in fibrous stepta, hepatic sinusoid and partial vascular endothelial cells, part of proliferating ductular epithelial cells and impaired hepatocytes. The positive staining began to increase from the first week. The expression of NF-κB in the liver tissues in PDTC group was lower than that in model control group (P<0.05). The ET levels and expression of NF-κB and CTGF began to increase significantly in liver fibrosis group. The levels of plasma ET and expression of NF-κB and CTGF were correlated positively with each other. In PDTC group, ET content in plasma increased significantly at first, then began to decline at the end of the test. The expression of NF-κB and CTGF in liver tissues in PDTC groups was lower than that in model group. Furthermore, the expression of NF-κB in liver tissues in PDTC group was correlated positively with CTGF. The levels of plasma ET were not correlated with the expression of NF-κB and CTGF.CONCLUSION: ET may up-regulate the expression of CTGF by activating NF-κB.
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Objective To study the level and clinical significance of serum interleukin-18(IL-18)in patients with acute cerebral infarction.Methods The level of serum IL-18 in patient with acute cerebral infarction(n=90)and normal controls group(n=45)were detected by enzyme linked immunosorbent assay.Results The level of serum IL-18 in large,medium and small lesion group were(288.4±59.3);(237.5±58.0);(186.9±50.6)ng/L respeetlvely,which were significantly higher than those in normal control group.The level of serum IL-18 in control group was(147.2±42.8)ng/L(P＜0.05).large lesion group was significantly higher than that in medium and small lesion group(P＜0.05).medium lesion grouP was significantly higher than that in small lesion group(P＜0.05).The levd of serum IL-18 in heavy,medium and light group were(284.9±57.3);(233.4±55.9);(184.5±48.3)ng/L respectively,which were significantly higher than those in normal control group(P＜0.05);heavy group was slgnificantly higher than that in medium and light group(P＜0.05),medium group was significantly higher than that in light group(P＜0.05).Conclusion The level of serum IL-18 was related to the severity of cerebral infarction,IL-18 may be involved in the pathogenesis of the hypoxic ischemic brain injury.
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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: 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 investigate the effects of antioxidant N-acetylcysteine(NAC)on the lipopolysaccharide(LPS)-induced MAPK phosphorylation in mouse liver.METHODS:54 male mice were divided into three groups:control(n=6),0.9% sodium chloride 0.2 mL ip;LPS group(n=24):LPS 5 mg ip;NAC+LPS group(n=24):NAC 150 mg?kg-1?d-1 ip,for 3 d;LPS 5 mg ip after 1 h of NAC administration at 3rd day.The liver was excised with carbrital anesthesia after LPS or 0.9 % sodium chloride injection at 0.5 h,1 h,2 h and 6 h for GSH and MDA assays.The protein extracted from liver was assayed for the phosphorylation of MEK1/2,ERK1/2,p38 MAPK by Western blotting.TNF-? in liver was assayed by radioimmunoassay.RESULTS:MDA in the liver was decreased remarkably and the GSH in the liver was increased significantly by NAC pretreatment.The phosphorylation of MEK1/2,ERK1/2 and p38 MAPK in liver were inhibited significantly by NAC pretreatment after LPS challenge.Meanwhile,TNF-? in liver was decreased markedly.CONCLUSION:Reactive oxygen species plays a critical role in MAPK signaling during the LPS induced acute liver injury.NAC partially inhibits LPS-induced MAPK signaling by antioxidant effect and decreases TNF-? production.
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AIM: To examine the effects of inhibition of Kupffer cell and splenectomy on intestinal endotoxemia and hepatic injury. METHODS: The hepatic injury model was established by treatment with thioacetamide (TAA). At the same time, inhibition of Kupffer cells by intravenous GdCl_3 and splenectomy were performed. Serum alanine aminotransferase (ALT), TNF-?, endotoxin content and phagocytic index were observed. RESULTS: In the TAA+GdCl_3 group, and TAA+splenectomy group, the endotoxin content was significently higher than that in normal and TAA group (P
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Changes of pulmonary vascular permeability and blood gas were measuredin rats of experimental fulminant hepatic failure induced by thioacetamide. The resultsshowed that the pulmonary vascular permeability to Evans Blue in rats of fulminant he-patic failure with hepatic enphalopathy was markedly increased than that of normalcontrols (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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Changes of glycosaminoglycans in cerebrum, brainstem and cerebellum were measured in rats with hepatic encephalopathy induced by thioacetamide. It was foundthat the contents of glycosaminoglycans in brainstem and cerebrum were lowered markedlythan that of the normal control, but no significant difference of glycosaminoglycans werefound in cerebellum. The results suggested that the metabolism of glycosaminoglycans incerebrum and brainstem was disturbed when hepatic encephalopathy occured, and thatthe pathogenic mechanism of hepatic encephalopathy was related to the alterations of gly-cosaminoglycans in brain as a result of hepatic insufficiency.
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AIM:To investigate the expression,distribution and significance of nuclear factor ?B (NF-?B) in experimental hepatic fibrosis.METHODS:Wistar rats were randomly divided into normal control group,hepatic fibrisis model group and the pyrrolidine-1-dithiocarboxylic acid ammonium sail (PDTC) group. The PDTC group was treated with subcutaneous injection of carboan tetrachloride,and treated with PDTC by oral administration. The content of hydroxyproline was measured. Endotoxin was determined with a Limulus amebocyte lysate test kit. The alanine aminotransferase (ALT) in plasma was measured by laishi method. The content of malondialdehyde (MDA) in liver tissue was detected by means of TBA method. The expression of NF-?B was determined by immunohistochemistry. The expression of connective tissue growth factor (CTGF) was measured by Western blotting.RESULTS:In control group,just a small amount of NF-?B p65 was expressed in the cytoplasm of a few hepatocytes around central veins. In model group,the positive staining of NF-?B p65 was expressed in cytoplasm and nucleus,mainly in fibrous stepta,hepatic sinusoid and partial vascular endothelial cells,part of proliferating ductular epithelial cells and impaired hepatocytes. The positive staining began to increase from the first week. The expression of NF-?B in the liver tissues in PDTC group was lower than that in model control group (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.