Asami A, Orii M, Shirasugi N, Yamazaki M, Akiyama Y, Kitajima M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
J Cardiovasc Surg (Torino). 1996 Jun;37(3):209-16.
Many studies show that allopurinol can reduce skeletal muscle I-R (ischemia-reperfusion) injury, but the mechanism of the effect is still unclear and some studies suspect the effect. In this study, we determined whether allopurinol really reaches to reperfused muscle and reduces tissue injury by inhibiting xanthine oxidase or not.
In this study, microdialysis method combined with HPLC (high performance liquid chromatography) were employed and purines, MDA (malondialdehyde), allopurinol in gracilis muscle were measured continuously in I-R injury model of canine gracilis muscle. The effect was compared between Group N (no treatment: n=8), Group P (pre-ischemic treatment: n=8) and Group R (pre-reperfusion treatment: n=8).
Allopurinol reduced the increase of xanthine, uric acid, MDA in the muscle and CPK in blood effluent from gracilis muscle after reperfusion. Tissue protecting effect of allopurinol was more effective in group R than in group P.
By continuous measurement of purines, allopurinol and MDA in canine gracilis muscle during 5 hr ischemia and 2 hr reperfusion, it was proved that allopurinol was delivered to reperfused skeletal muscle and reduced I-R injury by inhibiting xanthine oxidase.
许多研究表明，别嘌醇可减轻骨骼肌缺血再灌注损伤，但其作用机制仍不清楚，且一些研究对此作用表示怀疑。在本研究中，我们确定别嘌醇是否真的能到达再灌注的肌肉，并通过抑制黄嘌呤氧化酶来减轻组织损伤。
在本研究中，采用微透析法结合高效液相色谱法，在犬股薄肌缺血再灌注损伤模型中连续测定股薄肌中的嘌呤、丙二醛（MDA）和别嘌醇。比较了N组（未治疗：n = 8）、P组（缺血前治疗：n = 8）和R组（再灌注前治疗：n = 8）之间的效果。
别嘌醇减少了再灌注后股薄肌中黄嘌呤、尿酸、MDA的增加以及股薄肌流出血液中肌酸磷酸激酶（CPK）的增加。别嘌醇的组织保护作用在R组比在P组更有效。
通过在犬股薄肌5小时缺血和2小时再灌注期间连续测定嘌呤、别嘌醇和MDA，证明别嘌醇可输送至再灌注的骨骼肌，并通过抑制黄嘌呤氧化酶减轻缺血再灌注损伤。
