Functional role of thromboxane production by acutely rejecting renal allografts in rats.
Functional role of thromboxane production by acutely rejecting renal allografts in rats.
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大鼠急性排斥肾同种异体移植物产生血栓素的功能作用。
DOI：
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发表时间：
1985
影响因子：
15.9
通讯作者：
P. Klotman
中科院分区：
文献类型：
--
作者：
T. Coffman;W. Yarger;P. Klotman
我们研究了血栓素在肾移植急性排斥反应肾功能和肾血流特征降低中的作用。我们将Lewis大鼠的肾脏移植给了Brown-挪威的受者。移植后第三天，肾脏出现与细胞排斥反应相一致的组织学变化。这些变化与肾功能的适度下降有关。到第6天，排斥反应的组织学改变进展，包括单个核细胞的间质和血管周围的浸润。菊粉和对氨基马尿酸的清除量也明显降低。随着移植肾功能的恶化，移植肾体外灌流产生的血栓素B2(TXB2)在移植后2~6d逐渐增加。然而，前列腺素E2和6-酮前列腺素F1α的产量基本保持不变。菊粉在体内的清除量与体外TXB_2产生的对数呈显著负相关。经肾动脉注入血栓素A合成酶抑制剂UK-37248-01后，移植肾尿TXB_2排泄量显著减少，肾血流量和肾小球滤过率显著增加。尽管急性应用UK-37248-01后肾功能明显改善，但肾小球滤过率和肾小球滤过率均未超过正常对照组的33%和58%。在其他动物中，每天用环磷酰胺治疗可以改善菊糖和对氨基马尿酸的清除，并减少6天同种异体肾移植产生的血栓素。这些研究表明，排斥反应的组织学证据与肾脏血栓素的产生增加有关。抑制血栓素合成酶可改善3-d同种异体移植肾功能。细胞毒治疗可改善肾功能，减少单个核细胞的浸润，并减少同种异体移植物血栓素的产生。因此，强大的血管收缩因子血栓素A2可能在移植肾急性排斥反应中肾功能和肾血流的损害中起作用。
We investigated the role of thromboxane in mediating the reduction in renal function and renal blood flow characteristic of acute renal allograft rejection. We transplanted kidneys from Lewis rats to Brown-Norway recipients. By the third day after transplantation, histologic changes that were consistent with cellular rejection occurred in the kidney. These changes were associated with a moderate reduction in renal function. By day 6, histologic changes of rejection were advanced and included interstitial and perivascular infiltration by mononuclear cells. The clearances of inulin and para-aminohippuric acid were also markedly reduced. As renal function deteriorated, thromboxane B2 (TXB2) production by ex vivo perfused renal allografts increased progressively from 2 to 6 d after transplantation. However, prostaglandin (PG) E2 and 6-keto PGF1 alpha production remained essentially unchanged. There was a significant inverse correlation between the in vivo clearance of inulin and the log of ex vivo TXB2 production. Infusion of the thromboxane synthetase inhibitor UK-37248-01 into the renal artery of 3-d allografts significantly decreased urinary TXB2 excretion and significantly increased renal blood flow (RBF) and glomerular filtration rate (GFR). Although renal function improved significantly after the acute administration of UK-37248-01, GFR and RBF did not exceed 33 and 58% of native control values, respectively. In other animals, daily treatment with cyclophosphamide improved the clearances of inulin and para-aminohippuric acid and reduced thromboxane production by 6-d renal allografts. These studies demonstrate that histologic evidence of rejection is associated with increased renal thromboxane production. Inhibition of thromboxane synthetase improves renal function in 3-d allografts. Cytotoxic therapy improves renal function, reduces mononuclear cell infiltration, and decreases allograft thromboxane production. Thus, the potent vasoconstrictor thromboxane A2 may play a role in the impairment of renal function and renal blood flow during acute allograft rejection.
单侧输尿管结扎改变大鼠肾小球的前列腺素合成。
DOI：
10.1152/ajprenal.1981.241.3.f289
发表时间：
1981
期刊：
The American journal of physiology
影响因子：
--
作者：
Folkert,VW;Schlondorff,D
通讯作者：
Schlondorff,D
影响因子：
15.9
作者：
LIANOS, EA;ANDRES, GA;DUNN, MJ
通讯作者：
DUNN, MJ