Attenuation of hepatic fibrosis through ultrasound-microbubble-mediated HGF gene transfer in rats.

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.