Honour A J, Hockaday T D
Br J Exp Pathol. 1976 Feb;57(1):1-10.
In 14 rabbits previously injected intravenously with alloxan (dose 75-150 mg/kg) with subsequent hyperglycaemia, intra-arteriolar aggregation of platelets at the sites of small standardized electrical injuries to cerebral cortical vessels showed an increased sensitivity (P is less than 0.001) to application of adenosine diphosphate (ADP) in animals anaesthetized with either urethane or Pentothal. Intravenous injection of streptozotocin (10 rabbits, dose 30-200 mg/kg) was not followed so regularly by hyperglycaemia but even so many of these animals also showed increased sensitivity to ADP. After neither alloxan nor streptozotocin did the increased sensitivity correlate with the dose of agent used, the time between its injection and ADP testing, or changes in the rabbit's body weight. Again, ADP sensitivity did not correlate with the degree of hyperglycaemia, hyperketonaemia or hyperlactacidaemia. There was no rapid change in ADP sensitivity after i.v. injection of glucose to produce hyperglycaemia in normal rabbits, nor after parenteral or topical administration of insulin. Use of a removable skull capsule allowed serial observations on individual animals and these, together with observations on rabbits injected first with alloxan and later with daily insulin, showed reversibility of the increased ADP sensitivity by regular insulin injection for at least 5 days; this effect did not depend upon return of blood glucose levels to normal. In cross-perfusion experiments the increased ADP sensitivity was found to be dependent upon a blood factor for such sensitivity was shown by the head of a normal rabbit perfused with blood from a diabetic trunk. The results did not exclude a contribution of a mural factor to the results in intact animals after alloxan. The results are in keeping with in vitro observations of increased sensitivity to ADP of platelet aggregation in diabetic patients and demonstrate that such an effect holds within living blood vessels, as well as providing a model for further experiment.
在14只先前经静脉注射四氧嘧啶（剂量为75 - 150毫克/千克）随后出现高血糖的兔子中，对大脑皮质血管进行小型标准化电损伤部位的小动脉内血小板聚集显示，在用氨基甲酸乙酯或硫喷妥钠麻醉的动物中，对应用二磷酸腺苷（ADP）的敏感性增加（P小于0.001）。静脉注射链脲佐菌素（10只兔子，剂量为30 - 200毫克/千克）后，高血糖的出现并不那么规律，但即便如此，这些动物中的许多也表现出对ADP的敏感性增加。无论是注射四氧嘧啶还是链脲佐菌素后，敏感性的增加都与所用药物的剂量、注射药物与ADP测试之间的时间，或兔子体重的变化无关。同样，ADP敏感性也与高血糖、高酮血症或高乳酸血症的程度无关。在正常兔子静脉注射葡萄糖以产生高血糖后，以及在肠胃外或局部注射胰岛素后，ADP敏感性均未出现快速变化。使用可移除的颅骨胶囊可以对个体动物进行连续观察，这些观察结果以及对先注射四氧嘧啶后每日注射胰岛素的兔子进行观察的结果表明，通过定期注射胰岛素至少5天，可使增加的ADP敏感性恢复正常；这种效果并不取决于血糖水平恢复正常。在交叉灌注实验中，发现增加的ADP敏感性取决于一种血液因子，因为用糖尿病动物躯体的血液灌注正常兔子的头部时，也显示出这种敏感性。结果并不排除壁层因子对四氧嘧啶处理后的完整动物实验结果有影响。这些结果与糖尿病患者血小板聚集对ADP敏感性增加的体外观察结果一致，并表明这种效应在活体血管内也存在，同时还提供了一个进一步实验的模型。
