title: Effects of traditional chinese medicine on endotoxin and its receptors in rats with non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  The aim of this research is to study the effects of traditional Chinese medicine on endotoxin and its receptors in rats with nonalcoholic steatohepatitis (NASH).
  
  
  METHODS
  Fifty-six SD rats were divided into seven groups. All the animals were fed high fatty diet for 12 weeks. Rats with non-alcoholic steatohepatitis (NASH) were treated with traditional Chinese medicine according to low-dose, middle-dose, high-dose and Lipitor from fifth week. All rats were killed at the end of 12th week. The liver pathology changes were observed under light microscope. The levels of serum lipoid, alanine aminotransferase (ALT), endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukine-1beta (IL-1beta) were determined. The expressions of CD14 and nuclear transcriptional factor kappaB (NF-kappaB) were observed by immunohistochemistry. The expressions of lipopolysaccharide binding protein (LBP), toll-like receptor-4 (TLR-4), myeloid differentiation-2 (MD-2) and induced nitric oxide synthase (iNOS) mRNA were detected by the reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  The levels of serum endotoxin in the middle dose group (0.0225 +/- 0.0112 EU/l) were lower than those in high fatty diet model group (0.2249 +/- 0.0982 EU/l) at 12th week, the difference was significant (P < 0.01). In the middle dose group, mean values of serum TNF-alpha and IL-1beta levels decreased dramatically (1.604 +/- 0.302 ng/ml and 0.052 +/- 0.024 ng/ml) compared with those in the high fatty diet model group (4.029 +/- 1.180 ng/ml and 14.944 +/- 0.491 ng/ml; P < 0.01 and P < 0.01). The expressions of CD14 and NF-kappaB in the middle dose group decreased compared with those in the high fatty diet model group. The expressions of LBP mRNA (0.284 +/- 0.105) and TLR-4 mRNA (0.290 +/- 0.123) in the middle dose group down regulated compared with those in the high fatty diet model group (1.060 +/- 0.158 and 1.261 +/- 0.368; P < 0.01 and P < 0.01). In the middle dose group MD-2 and iNOS gene expressions were 0.132 +/- 0.058 and 0.164 +/- 0.061, respectively, which were significantly lower compared with the high fatty diet model group (0.795 +/- 0.294 and 1.029 +/- 0.388; P < 0.01 and P < 0.01).
  
  
  CONCLUSIONS
  The mechanism of non-alcoholic steatohepatitis (NASH) maybe related to increasing the levels of serum endotoxin, upregulating endotoxin receptors of hepatic tissue and enhancing liver inflammatory injury. Traditional Chinese medicine is a good treatment for non-alcoholic steatohepatitis (NASH). It can produce a marked effect via relieving LPS-induced liver injury.
authors.affiliation: Dalian Medical University, Dalian, Liaoning 116044, China. gaoyuan.laury@163.com
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Lin-Xuan
authors.initials: LX
authors.lastname: Song
authors.forename: Miao-Na
authors.initials: MN
authors.lastname: Jiang
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Ge
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Jia
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000069059:Atorvastatin; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004731:Endotoxins / Q000097:blood*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000097:blood; D008055:Lipids / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000410:Alanine Transaminase; D000069059:Atorvastatin; D002352:Carrier Proteins; D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D004731:Endotoxins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D011758:Pyrroles; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C495347:Tlr4 protein, rat; C048071:endotoxin receptor; C496318:Nos2 protein, rat