ABSTRACT
ObjectiveToexplorethedynamicchangesofoxidativestressandcytokinesinMongoliangerbilswith nonalcoholic fatty liver disease ( NAFLD) and their significance.Methods Forty-eight healthy male gerbils were randomly divided into normal group and model group , 24 in each group .Gerbils of the model group were fed with high fat diet while those of the normal group with normal diet .Eight gerbils in each group were killed at the end of 4 w, 8 w and 16 w, respectively .MDA content and SOD , GSH-PX and T-AOC activity in the liver tissue were detected by chemical method, and serum TNF-α, INF-γand IL-10 levels were determined using liquid suspension chip .Results With the development of NAFLD , MDA content in liver increased gradually , and the MDA contents were all significantly higher than those of the normal group ( P<0.01 ); T-AOC level slightly increased , and then decreased , the levels at 4 w and 16 w were markedly decreased compared with those of the normal group (P<0.05);SOD level was significantly increased and then markedly reduced, the level of the model group at 4 w was significantly increased (P<0.05), while that at 8 w and 16 w were significantly decreased (P<0.05, P<0.01).The level of GSH-PX was decreased gradually , the levels at 8 w and 16 w were significantly lower than those of the normal group (P<0.05).With the progression of NAFLD,serum TNF-αand IFN-γwere increased gradually , while the level of IL-10 decreased gradually , and the levels at 8 w and 16 w were significantly lower than those of the normal group ( P <0.05, P <0.01).Conclusions The oxidative stress-related indicators and inflammatory cytokines in the gerbil NAFLD models induced by high fat diet are significantly changed as simple fatty liver develops into steatohepatitis , liver fibrosis and cirrhosis , and participate in the development and progression of NAFLD .
ABSTRACT
Objective To explore the effect of high fat diet on serum biochemical parameters and histopathology of main organs in Mongolian gerbils.Methods Forty-eight healthy adult male Mongolian gerbils were randomly and equally divided into model and normal groups.The gerbils in the model group were fed with high fat diet while the normal group with standard diet.Eight gerbils in each group were killed at the end of 4th,8th and 16th week,respectively,and the body weight, serum levels of Glu, TG, CHOL, HDL-C, LDL-C, UA, CREA, BUN, TBil, TP, ALB, ALT, AST and AMS were determined.The histopathological changes of main organs were observed.Results Compared with the normal group,the blood lipid of the model gerbils was significantly increased, the liver function was impaired, the blood uric acid level was higher, and the blood glucose was decreased at the end of 16th week.The AMS was increased at the end of 16th week,but the renal function showed no significant changes.The liver tissue of the model group gradually showed steatosis, inflammation, fibrosis and cirrhosis, accompanied by splenomegalia. The lung tissue and myocardium showed fatty degeneration and obvious damages in the later period,the pancreatic islets were enlarged and the amount of endocrine cells was increased,and the small intestine and kidney didn’ t show any distinct changes.Conclusions A gerbil models of hyperlipidemia and nonalcoholic steatohepatitis and cirrhosis can be well established by high fat diet feeding,and may serve as good models for research of hyperlipidemia-related hyperuricemia, and lung and myocardial damages.
ABSTRACT
Objective To observe the expression of insulin-like growth factor 1 (IGF-1),insulin-like growth factor binding protein 3 ( IGFBP-3) in rats’ serum with non-alcoholic fatty liver disease ( NAFLD) and the impact of Polyene phosphatidyl choline .Methods NAFLD model was induced by feeding the SD rats with a high-fat diet, with Polyene phosphatidyl choline to intervene .Observe the pathological changes of the rats ’ liver tissue dynamically after HE staining . Detect the contents of IGF-1,IGFBP-3 in serum dynamically through the immuno radio metric assay ( IRMA).Results There were no obvious exception of the liver tissue pathology in the normal group at each time .With the extension of a high-fat diet,the liver tissue of the model group increased on fatty change ,the degree of inflammation ,the balloon sample change , the NAFLD activity score at 4,8,12weeks.IGF-1,IGFBP-3 in serum were decreased significantly ,and the model set was significantly lower than the normal group at the same phase .After the application of polyene phosphatidyl choline ,the degree of rat liver tissue inflammation and the NAFLD activity score were reduced significantly when compared with model group , while the level of IGF-1,IGFBP-3were significantly higher .Conclusion The levels of IGF-1,IGFBP-3 in the rats’ serum reduce in the development of non-alcoholic fatty liver disease .
ABSTRACT
<p><b>OBJECTIVE</b>To study the expression of uncoupling protein 2 (UCP2) in liver of rats with nonalcoholic steatohepatitis (NASH) induced by fat-rich diet, and the effect of total flavones of hawthorn leafon (TFHL) on UCP2.</p><p><b>METHOD</b>The NASH model of rat was induced by 12 weeks of fat-rich diet. Subsequently the rats were administrated with TFHL in accordance with 250, 125 mg x kg(-1) x d(-1) and the Essentiale N with 195.4 mg x kg(-1) x d(-1). The change of liver pathological. The levels of serum ALT and AST, the content of TG, CHOL, MDA and T-AOC activity of liver and were evaluated. The UCP2mRNA expression in liver was detected with RT-PCR, and the contents of UCP2 were examined with ELISA.</p><p><b>RESULT</b>There are severe steatosis, inflammatory cellular infiltration in the liver of the NASH models. The levels of serum ALT, AST and the contents of TG, CHOL, MDA and UCP2 in the model group were higher than those of in the normal groop. The expression of UCP2mRNA was obviously enhanced and the activity of T-AOC decreased. The expression of UCP2 mRNA of rats was positively correlation with the contents of MDA, TNF-alpha. The inflammation activity in rat liver, the contents of MDA and UCP2, the expression of UCP2 mRNA in the administrated groups were obviously lower than those in the model group, while the activity of T-AOC was higher than that of model.</p><p><b>CONCLUSION</b>TFHL may alleviate liver injury by means of the suppression of Oxidative stress/lipid peroxidation reaction and the overexpression of UCP2 in liver, which could prevent the further development of NASH.</p>
Subject(s)
Animals , Male , Rats , Crataegus , Chemistry , Enzyme-Linked Immunosorbent Assay , Fatty Liver , Drug Therapy , Metabolism , Flavones , Chemistry , Therapeutic Uses , Gene Expression , Ion Channels , Genetics , Liver , Metabolism , Mitochondrial Proteins , Genetics , Plant Leaves , Chemistry , Polymerase Chain Reaction , Rats, Sprague-Dawley , Uncoupling Protein 2ABSTRACT
Objective To investigate the effects of the therapy of invigorating the kidney and qi and dissipating blood stasis to removing the toxin on the hepatocyte apoptosis and associated genes in the liver fibrosis rats,and to explore the treatment mechanism of liver fibrosis with TCM.Methods liver fibrosis model rats were induced by CCl4,and the Chinese herbs(Ganlike)with invigorating the kidney and qi and dissipating blood stasis to removing the toxin was given by daily gavage,after the experiment,the pathological changes of liver were observed with optical microscope.Hepatocyte apoptosis was detected with TUNEL assay,apoptosis-associated genes were detected with immunohistochemistry assay.Results The Chinese herbs Ganlike could obvously improve the pathological changes,alleviate the hepatocyte apoptosis and modulate the expression of apoptosis-associated genes.Conclusions The anti-fibrosis mechanism of Ganlike may be to regulate the hepatocyte apoptosis of liver fibrosis rats and to restrain the expressions of hepatocyte Fas/FasL,Bcl-2/Bax.
ABSTRACT
Objective To measure the the expression of TNF-?、IL-6mRNA in liver of rats with alcohol fatty liver, and the amounts of TNF-?and IL-6, to observe the lesion of lipid superoxidation, to explore the pathogenesis of alcohol fatty liver. Methods 23 of SD rats were divided into the normal group(10) and the model group(13),all the rats in the model were given 50% alcohol by daily gavage, and drank 10% alcohol, after 14 weeks, all the rats were killed and the pathological change of liver were observed, the amounts of serum TG,TC,ALT,AST,FFA,MDA,SOD,GSH-PX,TNF-? and IL-6 were examined, the expression of TNF-?、IL-6mRNA was measured. Results In the model ,to different degree, there were some fatty steatosis , the amounts of TG、FFA、MDA、TNF-?and IL-6 were higher than that in the normal group, but the amounts of SOD and GSH-PX lower, in comparison with the normal, the expression of TNF-?mRNAand IL-6mRNA in liver of model were significantly increased. Conclusions long-term of ingestion of potation maybe cause the disorder of lipid metabolic system and alcohol fatty liver came into being. Simultaneously with the enhancement of oxidation stress/lipid superoxidation and abnormity of secretion of some cytokine such as TNF-?and IL-6.
ABSTRACT
Objective:To observe the expression of cytochrome P4502E1 (CYP2E1) in the liver tissue of rats with non-alcoholic steatosis hepatitis (NASH) induced by high-fat diet, and effect of total flavonoids of Chinese hawthorn leaf(TFHL). Methods: The model rats of NASH were induced by 12 weeks' high-fat diet, and treated with TFHL and Essentiale. The pathological changes of rats liver were observed, the amounts of liver MDA, and the activities of SOD, GSH-Px were detected, the mRNA and protein expressions of CYP2E1 were detected with RT-PCR and immunochemical method. Results: ①there were serious steatosis, different degree of infiltration of inflammatory cells and necrosis focus in the livers of model rats, the amounts of liver MDA was higher than that of the normal group, the acttivities of SOD, GSH-Px in the livers were lower, the expressions of mRNA and protein were strengthened. ②the expression of CYP2E1 of livers has a positive correlation with the amount of MDA, but negative correlation with the activity of SOD and GSH-Px. ③the inflammation of liver, the amounts of liver MDA level, the mRNA and protein expressions of CYP2E1,the activity of SOD and GSH-Px in rats treated with high or low dose TFHL were obviously lower than the model rats, but the activities of SOD and GSH-Px were higher than the model rats.Conclussion: CYP2E1 takes part in the onset and development of NASH induced by high-fat diat, TFHL can restrain the activity of CYP2E1 and the lipid peroxidization, enhance the ability of antioxygenation of liver cells, and prevent the further development of NASH.
ABSTRACT
Objective:To study the effect of NF-?B and its inhibitor in rats liver during the development of non-alcoholic steato-hepatitis and observe the effect of total flavonoids of Chinese hawthorn leaf on expressions of NF-?B and its inhibitor,and explore the prevention and treatment mechanism of non-alcoholic steato-hepatitis. Methods:Non-alcoholic steato-hepatitis SD rats model were established by administering a high-fat diet for 12 weeks and were treated with total flavonoids of Chinese hawthorn leaf at dosages of 250mg/kg body weight /d,125 mg/kg body weight /d and with Essentiale at a dosage of 195.4mg /kg body weight /d. Pathological changes of liver tissues were observed with HE,the serum MDA,SOD and TNF-? were measured,the protein and mRNA expressions of NF-?B and I?B in rats liver were detected with RT-PCR and immunohistochemical method. Results:There were severe steatosis inflammatory cell infiltration and necrotic foci in non-alcoholic steato-hepatitis rat. Compared with the control group,contents of the serum MDA and TNF-? in non-alcoholic steato-hepatitis group obviously increased,the activity of SOD decreased,the mRNA and protein expressions of NF-?B P65 and I?B? in liver obviously strengthened. There was a positive relativity of the protein expression of NF-?B p65,I?B? with the contents of serum TNF-?,MDA,but a negative relativity with the activity of serum SOD. Conclusion:Total flavonoids of Chinese hawthorn leaf can obviously lower lipid peroxidation in rats,lower the harm of cytokine to hepatocytes,and regulate the expression of protein and mRNA of NF-?B and I?B. It maybe the important mechanism of total flavonoids of Chinese hawthorn leaf for preventing and treating the development of non-alcoholic steato-hepatitis.
ABSTRACT
Objective:To study the effect of compound Biejiaruangan tablets on the expression of liver AngiotensionII and its receptor in rats with hepatic fibrosis,and to explore the mechanism of its anti-hepatic fibrosis.Methods: Thirty male SD rats were randomly divided into three groups as followings: the normal group,the model group and the compound Biejiaruangan tablets group,all rats in the two latter groups were given subcutaneous injection of 40%carbon tetrachloride(twice every week for 6 weeks),the rats in the compound Biejiaruangan tablets group were given 1g?kg-1?d-1 of the compound Biejiaruangan tablets by daily gavage,the rats in normal control group and the model group were given distilled water according to the same volume,the histopathological changes in liver were observed through HE and Massion staining.The serum ALT,AST and ALP were evaluated by antomatic biochemistry analysator,the serum levels of hyaluronic acid (HA),Laminin(LN) and plasm AngiotensionII(Ang-Ⅱ) were determined by radio immunoassay.The expressions of AngⅡ,AT1R mRNA were examined by RT-PCR.Results:The severity of inflammation scoring,hepatic fibrosis scoring,the amounts of serum ALT,AST,ALP,HA,LN and plasma AngⅡ in the liver tissues of hepatic fibrosis model group were higher than those in the normal group(P