In Vivo Assessment of the Effects of Ginsenoside Rb1 on Intimal Hyperplasia in ApoE Knockout Mice

Abstract

This study investigated the effects of ginsenoside Rb1 (Rb1) on injury-induced intimal hyperplasia in ApoE knock out (ApoE -/-) mice. We also examined the value of an ultrasound micro-image system in dynamic monitoring of lumen diameter and flow velocity. After guide wire injury of the distal left common carotid artery (CCA), ApoE-/- mice were treated with intraperitoneal infusion of normal saline (NS), homocysteine (Hcy), ginsenoside Rb1 (Rb1), or Hcy+Rb1 for 4 wk. Bilateral CCA luminal diameters and flow velocities were measured with an ultrasound micro-image system before surgery and weekly afterwards. Following the final ultrasound, CCAs were harvested and analyzed for intima-medium thickness ratios. Progressive reduction in luminal diameters and increase in flow velocity of the injured left distal CCA segment were observed using ultrasound micro-imaging system in all groups compared with the relatively stable left proximal CCA and right CCA. The NS and Hcy groups had significantly higher degree of diameter reduction compared with the Rb1 and Rb1+Hcy groups. The ultrasound findings were consistent with histology analyses at 4 wk post-op. The study suggested that Rb1 attenuated the effects of Hcy on injured carotid arteries of ApoE -/- mice. The study also showed that ultrasound micro-image system was a reliable tool in monitoring luminal reduction after injury in a murine model. This study establishes a fundamental step of in vivo monitoring of the therapeutic effects of agents in a murine model without sacrificing the animals.