title: Attenuation of hepatic fibrosis through ultrasound-microbubble-mediated HGF gene transfer in rats.
abstract: OBJECTIVE
  The objective was to explore the feasibility of ultrasound-microbubble-mediated hepatocyte growth factor (HGF) gene transfer for treating rat hepatic fibrosis induced by CCl(4).
  
  
  METHODS
  Forty-eight male SD rats were divided into ultrasound-microbubble-HGF group (U-M-HGF group), ultrasound-HGF group (U-HGF group), microbubble-HGF group (M-HGF group), HGF group (HGF group), CCl(4) group (control group), and normal group. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total protein, albumin (ALB), and globulin (GLB) and the ratio of ALB/GLB were determined after treatment. The degree of hepatic fibrosis was evaluated by histopathological numerical scores. The protein expressions of HGF, collagen I, collagen III, and α-smooth muscle antibody (α-SMA) were detected by immunohistochemistry.
  
  
  RESULTS
  Ultrasound-microbubble-mediated HGF therapy significantly reduced the serum level of ALT and AST to 59.88% and 49.18% of the control group, respectively. Ultrasound-microbubble-mediated HGF therapy prevented liver fibrosis, with an obvious decrease in fibrosis areas and extracellular matrix production of collagen I, collagen III, and α-SMA. The gene therapy could induce HGF delivery into the fibrotic liver effectively.
  
  
  CONCLUSIONS
  Ultrasound-microbubble-mediated HGF gene therapy can reduce liver fibrosis, which provides a novel strategy for gene therapy of chronic liver disease.
authors.affiliation: School of Medicine, Shaoxing University, Shaoxing, Zhejiang, China; First Clinical Medical Institute, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Zhen-zhen
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: Guo-yuan
authors.initials: GY
authors.lastname: Xia
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.forename: Ben-zhen
authors.initials: BZ
authors.lastname: He
authors.forename: Jian-gang
authors.initials: JG
authors.lastname: Sun
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D018274:Electroporation / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D045423:Microbubbles; D010743:Phospholipids; D051381:Rats; D013010:Sonication / Q000379:methods*; D013459:Sulfur Hexafluoride; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: C066855:HGF protein, human; D010743:Phospholipids; C420843:contrast agent BR1; D017228:Hepatocyte Growth Factor; D004247:DNA; D013459:Sulfur Hexafluoride