Immune complex effects on glomerular eicosanoid production and renal hemodynamics.
Immune complex effects on glomerular eicosanoid production and renal hemodynamics.
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DOI：
10.1038/ki.1987.145
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发表时间：
1987-06
影响因子：
19.6
通讯作者：
M. A. Rahman;S. Emancipator;M. Dunn
中科院分区：
文献类型：
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作者：
M. A. Rahman;S. Emancipator;M. Dunn
免疫复合物对肾小球类二十烷酸产生和肾血流动力学的影响。我们研究了肾小球免疫复合物（IC）沉积对肾小球类二十烷酸合成的影响以及类二十烷酸在肾小球病理生理学中的作用。大鼠每天静脉注射 10 毫克注射天然牛丙种球蛋白（NBGG）或阳离子牛丙种球蛋白（CBGG）21天；维持年龄匹配的对照。免疫荧光和电镜显示NBGG组有IC系膜沉积，CBGG组毛细血管壁沉积，无光镜或电镜白细胞浸润证据。最后一次抗原剂量后一周，所有三组的 GFR 相似，但给予 CBGG 的大鼠 RPF 增加； （8.37 ± 0.90 对比对照 5.54 ± 0.56 毫升/分钟，P < 0.05）。在接受 NBGG 的动物中，前列腺素 E2 (PGE2) 和血栓素 B2 (TxB2) 的肾小球合成正常。给予 CBGG 的大鼠肾小球产生的 PGE2 增加（2.23 ± 0.37 对比对照 1.03 ± 0.16 ng/mg 肾小球干重，P < 0.05）和 TxB2（3.12 ± 0.50 对比对照 0.48 ± 0.07 ng/mg 肾小球干重，P < 0.001）。仅给予 CBGG（86.6 ± 18 mg/24 小时）的大鼠出现蛋白尿，这与肾小球 TxA2 合成相关，r = 0.82，P = 0.01。对给予 CBGG 的大鼠急性施用 TxA2 合成抑制剂 UK-38,485 和 TxA2 受体拮抗剂 EP-092 不会影响 GFR 或 RPF。环加氧酶抑制剂吲哚美辛可使 CBGG 免疫大鼠的 GFR 和 RPF 降低高达 40%。尽管肾小球 TxB2 受到 85% 的抑制，但肾病大鼠口服 UK-38,485 六天并没有导致蛋白尿出现统计上显着的减少。我们得出的结论是，阳离子抗原会诱发病理上类似于膜性肾病的肾小球疾病。 RPF 的增加很可能是由于肾小球 PGE2 增加所致。 TxA2 增加对肾小球血流动力学没有影响，可能不是蛋白尿发病机制的一个组成部分。
Immune complex effects on glomerular eicosanoid production and renal hemodynamics. We examined the effect of glomerular immune complex (IC) deposition on glomerular eicosanoid synthesis and the role of the eicosanoids in glomerular pathophysiology. Rats received daily 10 mg i.v. injections of native bovine gamma–globulin (NBGG) or cationic bovine gamma–globulin (CBGG) for 21 days; age–matched controls were maintained. Immunofluorescence and electron microscopy showed mesangial deposits of IC in the NBGG group and capillary wall deposits in the CBGG group, without light or electron microscopic evidence of leukocyte infiltration. One week after the last antigen dose, GFR was similar in all three groups, but RPF increased in the rats given CBGG; (8.37 ± 0.90 vs. control 5.54 ± 0.56 ml/min, P < 0.05). Glomerular synthesis of prostaglandin E2(PGE2) and thromboxane B2(TxB2) was normal in animals that received NBGG. Rats given CBGG had increased glomerular production of PGE2, (2.23 ± 0.37 vs. control 1.03 ± 0.16 ng/mg glomerular dry wt, P < 0.05) and TxB2(3.12 ± 0.50 vs. control 0.48 ± 0.07 ng/mg glomerular dry wt, P < 0.001). Proteinuria only developed in the rats given CBGG, 86.6 ± 18 mg/24 hr, which correlated with glomerular TxA2synthesis, r = 0.82, P = 0.01. Acute administration of the TxA2synthesis inhibitor, UK-38,485, and a TxA2receptor antagonist, EP-092, to rats given CBGG did not affect GFR or RPF. The cyclo-oxygenase inhibitor, indomethacin, reduced both GFR and RPF by up to 40% in CBGG-immunized rats. Oral administration of UK-38,485 for six days to nephrotic rats did not result in a statistically significant reduction of proteinuria despite 85% inhibition of glomerular TxB2. We conclude that cationic antigen induces a glomerular disease pathologically similar to membranous nephropathy. The increment of RPF is most probably due to increased glomerular PGE2. The increased TxA2has no effect on glomerular hemodynamics and probably is not a component in the pathogenesis of proteinuria.