Papanikolaou N
Prostaglandins Leukot Med. 1987 May;27(2-3):129-49. doi: 10.1016/0262-1746(87)90066-7.
Repeated subcutaneous (SC) injections of mercuric chloride (MC) in Brown Norway (BN) rats induce an autoimmune glomerulonephritis (GN) due to antiglomerular basement membrane (BM) antibody deposition in the glomeruli. The aim of this study was to investigate the effects on MC-induced autoimmune GN of OKY-046, a selective TXA-synthetase inhibitor herring oil (HO), which is rich in eicosapentaenoic acid (EPA) (5.6%) precursor of the three series of prostaglandins (PGs) and of (inactive) thromboxane (TXA3), and evening primrose oil (EPO), which is rich in linoleic acid (LA) (72%) and gamma-linolenic acid (GLNA) (9%), precursors of the one series of PGs, mainly PGE1, and of (inactive) TXA1. The administration of OKY-046 significantly inhibited proteinuria, partially prevented fibrin thrombi (FT) formation in the glomeruli, decreased urinary TXB, enhanced 6ketoPGF excretion and, increased survival rate of the animals from 60% (group receiving only MC) to 86%. However, OKY-046 did not prevent body weight (BW) loss or the development and deposition of IgG in the glomeruli. Increased intake of HO (80 days prior and throughout the experiment) and avoidance of arachidonic acid (AA) intake produced an effect comparable to that of OKY-046 in the rats. Furthermore, HO significantly inhibited the deposition of IgG in the glomeruli, increased the survival rate of the animals to 100% and further enhanced the increased urinary PGE excretion induced by MC. However, HO did not prevent BW loss in the animals. Increased intake of EPO and avoidance of AA intake produced an effect comparable to that of HO. Additionally, EPO completely prevented BW loss induced by MC in these animals. These findings suggest that the metabolites of AA, EPA and GLNA play an important role either in the development or in the modulation of this model of MC induced GN.
在棕色挪威（BN）大鼠中反复皮下注射氯化汞（MC）会引发自身免疫性肾小球肾炎（GN），这是由于抗肾小球基底膜（BM）抗体在肾小球中沉积所致。本研究的目的是调查选择性血栓素A合成酶抑制剂OKY - 046、富含二十碳五烯酸（EPA）（5.6%）（前列腺素（PGs）三个系列以及（无活性的）血栓素（TXA3）的前体）的鲱鱼油（HO）和富含亚油酸（LA）（72%）和γ-亚麻酸（GLNA）（9%）（PGs一个系列，主要是PGE1以及（无活性的）TXA1的前体）的月见草油（EPO）对MC诱导的自身免疫性GN的影响。给予OKY - 046可显著抑制蛋白尿，部分预防肾小球中纤维蛋白血栓（FT）形成，降低尿TXB，增强6 - 酮 - PGF排泄，并使动物存活率从60%（仅接受MC的组）提高到86%。然而，OKY - 046并不能防止体重（BW）减轻或IgG在肾小球中的形成和沉积。增加HO的摄入量（实验前80天及整个实验期间）并避免摄入花生四烯酸（AA）在大鼠中产生了与OKY - 046相当的效果。此外，HO显著抑制IgG在肾小球中的沉积，将动物存活率提高到100%，并进一步增强了MC诱导的尿PGE排泄增加。然而，HO并不能防止动物体重减轻。增加EPO的摄入量并避免摄入AA产生了与HO相当的效果。此外，EPO完全防止了这些动物中由MC诱导的体重减轻。这些发现表明，AA、EPA和GLNA的代谢产物在这种MC诱导的GN模型的发展或调节中起重要作用。
