VEGF als Stimulator der Leberregeneration: Intravitalmikroskopische Beobachtungen in Ratten

Background and aims: After partial hepatectomy (PH), clinical outcome, morbidity and mortality of the patients depend on an efficient regeneration of the liver. Angiogenesis is essential for the regeneration of the liver and Vascular Endothelial Growth Factor (VEGF) belongs to the most potent angiogenic factors. The aims of the study were to determine the effects of exogenous VEGF administration in rats after 2/3 hepatecomy on angiogenesis by intravital microscopy and on regeneration. Methods: Adult male Lewis rats (n = 5/group) were subjected to 70% PH and split in 3 groups. Group A (VEGF), group B (anti-VEGF), and group C (Control) were administered VEGF (100 ng/μl), anti-VEGF (4 μg/μl) or NaCl i.v. at 0 h, 36 h, and 96 h. At 0 h, 24 h, 48 h, 72 h, 120 h, 168 h postoperatively 5 rats each underwent intravital microscopy of the exposed liver remnant. Recorded parameters were: Vessel density (VD) and vessel diameter (VDi). Liver regeneration was monitored by measuring liver body weight ratio (LBR) and immunohistochemically by proliferating cell nuclear antigen (Ki-67). Additionally liver enzymes GOT, GPT, ?GT, GLDH as well as the functional parameter bilirubin were investigated in the serum. Results: In VEGF treated rats (group A), VD was significantly increased compared to group B or C (p < 0.05). VDi was significantly increased through 24–72 h in group A (p < 0.05) compared to group B and C. In the VEGF treated animals, LBR was increased after 48 h, 72 h and 120 h (p < 0.025). Ki-67 immunostaining showed a significantly higher labelling index of hepatocytes at 24 h after PH in VEGF treated animals with 82% compared to the anti-VEGF treated animals with only 3%. Liver enzymes GOT/GPT were doubled with 1000U/L and 600U/L in anti-VEGF treated animals. Conclusion: Exog-enous VEGF administration leads to increased angiogenesis, which subsequently results in faster and improved liver regeneration. This effect can be blocked by anti-VEGF. Therefore, VEGF treatment may provide a novel strategy for optimization of liver regeneration in patients after PH.