Itoh H, Komori K, Okazaki J, Mawatari K, Kawasaki K, Kuma S, Eguchi D, Sugimachi K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Cardiovasc Surg. 1997 Oct;5(5):497-503. doi: 10.1016/s0967-2109(97)00059-8.
Probucol is used to treat hypercholesterolemia and also has an anti-atherogenic effect. The effects of probucol on intimal thickening of autologous vein graft in hyperlipidemic rabbits with poor distal run-off were investigated. A poor distal run-off model was prepared in the right hindlimb of 18 rabbits allocated to four groups depending on diet: normolipidemic commercial diet, (NL group, n = 5); hyperlipidemic diet (HL group, n = 5); commercial diet with 1% probucol (NP group, n = 4); and hyperlipidemic diet with 1% probucol (HP group, n = 4). After 4 weeks the femoral vein grafts were implanted into normal (n = 18) or poor (n = 18) runoff limbs. Vein grafts were harvested 4 weeks after implantation. Intimal thickening of the graft was measured and macrophages therein examined immunohistochemically. The serum cholesterol level was not reduced by probucol treatment. The mean flow rate of the graft was significantly reduced in the poor run-off limb. On histological examination intimal thickening in the poor run-off limb was significantly greater than that of controls, while intimal thickening in the HL and HP groups was enhanced compared with that in the NL and NP groups, respectively. Mean intimal thickening in each limb in HP group rabbits was significantly lower than that in HL rabbits (microm): control (HL/HP): 99.4(7.4)/58.8(0.7) (P < 0.05); poor run-off (HL/HP): 155.3(9.6)/130.3(7.3) (P < 0.O5). There was no difference between NL and NP (microm): control (NL/NP): 44.6(24.7)/31.5(12.8); poor run-off (HL/HP): 115.3(13.8)/97.5(34.0). In addition, enhanced intimal thickening due to poor distal run-off was not suppressed. Immunohistochemical staining showed intimal macrophage infiltration in the HL and HP groups; however, macrophage infiltration in grafts in the HP group was less than in the HL group. In conclusion, under hyperlipidemic conditions, probucol decreased intimal thickening enhancement of the vein graft, and suppressed intimal macrophage infiltration. These findings were similar to the anti-atherogenic effect of probucol in the native artery. Hence, probucol administration after vascular reconstruction with vein grafts in patients with hyperlipidemia may be beneficial.
普罗布考用于治疗高胆固醇血症，且具有抗动脉粥样硬化作用。本研究探讨了普罗布考对远端血流不佳的高脂血症兔自体静脉移植物内膜增厚的影响。将18只兔的右后肢制备成远端血流不佳模型，根据饮食分为四组：正常血脂商业饮食组（NL组，n = 5）；高脂饮食组（HL组，n = 5）；含1%普罗布考的商业饮食组（NP组，n = 4）；含1%普罗布考的高脂饮食组（HP组，n = 4）。4周后，将股静脉移植物植入正常血流（n = 18）或血流不佳（n = 18）的肢体。植入后4周收获静脉移植物。测量移植物的内膜增厚情况，并通过免疫组织化学检查其中的巨噬细胞。普罗布考治疗未降低血清胆固醇水平。血流不佳肢体的移植物平均流速显著降低。组织学检查显示，血流不佳肢体的内膜增厚明显大于对照组，而HL组和HP组的内膜增厚分别比NL组和NP组增强。HP组兔各肢体的平均内膜增厚明显低于HL组兔（微米）：对照组（HL/HP）：99.4(7.4)/58.8(0.7)（P < 0.05）；血流不佳组（HL/HP）：155.3(9.6)/130.3(7.3)（P < 0.05）。NL组和NP组之间无差异（微米）：对照组（NL/NP）：44.6(24.7)/31.5(12.8)；血流不佳组（HL/HP）：115.3(13.8)/97.5(34.0)。此外，远端血流不佳导致的内膜增厚增强未被抑制。免疫组织化学染色显示HL组和HP组内膜有巨噬细胞浸润；然而，HP组移植物中的巨噬细胞浸润少于HL组。总之，在高脂血症条件下，普罗布考可减少静脉移植物内膜增厚的增强，并抑制内膜巨噬细胞浸润。这些发现与普罗布考在天然动脉中的抗动脉粥样硬化作用相似。因此，高脂血症患者在静脉移植物血管重建后给予普罗布考可能有益。
