title: Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats.
abstract: OBJECTIVE
  To evaluate the antifibrotic effect of telmisartan, an angiotensin II receptor blocker, in bile duct-ligated rats.
  
  
  METHODS
  Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats, model rats underwent common bile duct ligation (BDL), and BDL rats treated with telmisartan (8 mg/kg, po, for 4 weeks). The animals were sacrificed on d 29, and liver histology was examined, the Knodell and Ishak scores were assigned, and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining. The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot, respectively.
  
  
  RESULTS
  The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35, P=0.015). However, there was no significant difference in inflammation between the two groups, both of which showed moderate inflammation. Histologically, treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis. Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS, and decreased the mRNA levels of ACE, angiotensin II type 1 receptor (AT1-R), collagen type III, and transforming growth factor β1 (TGF-β1). Moreover, treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins, and inhibited the expression levels of ACE and AT1-R protein.
  
  
  CONCLUSIONS
  Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.
authors.affiliation: Department of Infectious Disease and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: En-tong
authors.initials: ET
authors.lastname: Yi
authors.forename: Rui-xia
authors.initials: RX
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.forename: Cheng-hong
authors.initials: CH
authors.lastname: Yin
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D001652:Bile Ducts / Q000601:surgery; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008026:Ligation; D008103:Liver Cirrhosis / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000077333:Telmisartan