Poelstra K, Baller J F, Hardonk M J, Bakker W W
Department of Pathology, University of Groningen, The Netherlands.
Lab Invest. 1991 Apr;64(4):520-6.
It has been proposed, predominantly from ex vivo studies, that glomerular ADPase may function as an antithrombotic principle within the rat kidney. Therefore, intraglomerular platelet aggregation was studied in vivo in rats after impairment of glomerular ADPase activity using local X-irradiation (20 Gy). Biochemical assays in suspensions of glomeruli obtained from rats 24 hours after local X-irradiation (group I) demonstrated a significant reduction in ADPase activity as compared to sham treated rats (group II; p less than 0.01). Cytochemical observations at the ultrastructural level showed that this reduction in glomerular enzyme activity represents in particular ADPase activity detectable in the basement membrane. Following X-irradiation, intraglomerular platelet aggregation was quantitatively studied in two groups of rats. Both groups received X-irradiation of the left kidney (20 Gy). Twenty-four hours after X-irradiation, animals received an intravenous injection of either 0.5 ml of saline (group III; N = 6) or 0.5 ml of heterologous nephrotoxic serum (NTS; group IV; N = 6). Subsequently, 24 hours after this injection, platelet aggregation in left kidneys was compared with aggregation in contralateral non-X-irradiated kidneys. The results showed that while X-irradiation per se did not induce intraglomerular platelet aggregation as compared with the contralateral kidney (0.20 +/- 0.08% versus 0.17 +/- 0.06% platelet aggregation/glomerulus), a significant increase in platelet aggregation could be demonstrated in X-irradiated kidneys in the early phase of nephrotoxic serum nephritis as compared with the contralateral nephritic kidney (2.45 +/- 0.66% versus 1.37 +/- 0.35% platelet aggregation per glomerulus; p less than 0.005). A potential effect of altered influx of inflammatory cells after X-irradiation could be excluded since no difference in H2O2 producing cells was observed between left and right kidneys. Thus, while ADPase impairment by X-irradiation does not induce platelet aggregation per se, it is clear that in proaggregatory conditions, like in NTS nephritis, the thrombotic tendency, due to decreased glomerular ADPase, is enhanced. These results demonstrate the functional significance of glomerular ADPase activity as an antithrombotic principle following platelet activation in vivo.
主要来自体外研究的结果表明，肾小球ADP酶可能作为大鼠肾脏内的一种抗血栓形成物质发挥作用。因此，利用局部X射线照射（20 Gy）损伤肾小球ADP酶活性后，在大鼠体内研究了肾小球内血小板聚集情况。对局部X射线照射后24小时的大鼠（I组）肾小球悬液进行生化分析，结果显示与假手术处理的大鼠（II组；p<0.01）相比，ADP酶活性显著降低。超微结构水平的细胞化学观察表明，肾小球酶活性的降低尤其表现为基底膜中可检测到的ADP酶活性降低。X射线照射后，对两组大鼠的肾小球内血小板聚集情况进行了定量研究。两组大鼠均接受了左肾的X射线照射（20 Gy）。X射线照射24小时后，给动物静脉注射0.5 ml生理盐水（III组；N = 6）或0.5 ml异种肾毒性血清（NTS；IV组；N = 6）。随后，在此次注射24小时后，将左肾中的血小板聚集情况与对侧未接受X射线照射的肾脏中的聚集情况进行比较。结果显示，与对侧肾脏相比，X射线照射本身并未诱导肾小球内血小板聚集（每肾小球血小板聚集率为0.20±0.08%对0.17±0.06%），但在肾毒性血清性肾炎早期，与对侧肾炎肾脏相比，X射线照射的肾脏中血小板聚集显著增加（每肾小球血小板聚集率为2.45±0.66%对1.37±0.35%；p<0.005）。由于未观察到左肾和右肾之间产生H2O2的细胞存在差异，因此可以排除X射线照射后炎症细胞流入改变的潜在影响。因此，虽然X射线照射导致的ADP酶损伤本身不会诱导血小板聚集，但很明显，在促聚集状态下，如在NTS肾炎中，由于肾小球ADP酶减少，血栓形成倾向会增强。这些结果证明了肾小球ADP酶活性在体内血小板激活后作为抗血栓形成物质的功能意义。
