环氧化酶及5-脂氧化酶对肾炎模型中肾小球iNOS表达的影响

EFFECTS OF CYCLOOXYGENATION AND 5 LIPOXYGENATION ON GLOMERULAR EXPRESSION OF THE GENE FOR INDUCIBLE NITRIC OXIDE SYNTHASE IN EXPERIMENTAL GLOMERULONEPHRITIS

目的：研究花生四烯酸（ ＡＡ） 环氧化酶产物及５脂氧化酶产物对大鼠加速性肾毒性血清性肾炎（ ＮＳＮ） 中肾小球诱生型一氧化氮合成酶（ｉＮＯＳ） 表达的影响。 方法：制备ＮＳＮ 大鼠模型后，应用消炎痛抑制ＡＡ环氧化酶，应用ＭＫ０９５１ 抑制ＡＡ 的５脂氧化酶，观察对肾小球ｉＮＯＳ 表达的影响。 结果：在ＮＳＮ 大鼠，应用消炎痛抑制环氧化酶，可减少肾小球合成的前列腺素（ＰＧ） Ｅ２ 及血栓素（ ＴＸ） Ｂ２ ，使肾小球ｉＮＯＳ 表达增强，尿亚硝酸盐（ ＮＯ－２ ） 排出增多；应用ＭＫ０９５１ 抑制５脂氧化酶，可减少肾小球合成的白三烯（ＬＴ） Ｂ４ ，也使肾小球ｉＮＯＳ 表达增强，尿ＮＯ－２ 增多。 结论：ＮＳＮ 大鼠肾小球合成的环氧化酶及５脂氧化酶产物ＰＧＥ２ 、ＴＸ 及ＬＴ 有抑制肾小球ｉＮＯＳ 表达的作用。

To investigate the effects of arachidonate cyclooxygenation and 5 lipoxygenation on golmerular expression of the gene for inducible nitric oxide synthesase(iNOS)in rats with accelerated nephrotoxic serum nephritis(NSN). METHODOLOGY The model of NSN was established in male SD rats with peritoneal injection of rabbit IgG and Freund complete adjuvant followed by intravenous injection of anti rabbit GBM antibody.Rats of NSN were grouped into:(1)NSN group( n =8);(2)NSN+INDO group ( n =8)in which NSN rats were pretreated with indomethacin (3mg/kg,a cyclooxygenase inhibitor)intravenously one hour before the injection of anti GBM antibody;and (3) NSN+MK( n =8)group in which the NSN rats were pretreated with MK 0951(a 5 lipoxygenase inhibitor)intravenously one hour before the injection of anti GBM antibody.Six rats administered with normal rabbit serum were set as the control.HPLC and radioimmunoassay were used in the determination of prostaglandin E2(PGE 2),leukotrience B4(LTB 4)and thronmboxane B2(TXB 2).Glomerular expression of iNOS was determined by RNAase protection assay. RESULTS Enhanced glomerular synthesis of PGE 2 and TXB 2,increased the urinary excretion of nitrite (NO 2),and up regulated glomerular expression of iNOS mRNA were found in NSN group as compared to the control.In NSN+INDO group in which cyclooxygenation was inhibited,glomerular synthesis of PGE 2 and TXB 2 was suppresseds glomerular expression of iNOS enhanced,glomerular synthesis of LTB 4 and urinary excretion of NO 2 increased.Pretreatment of nephritic rats with MK 0951,a 5 lipoxygenase inhibitor,reduced the enhanced glomerular synthesis of LTB 4,stimulated the iNOS induction and increased the urinary excretion of NO 2. CONCLUSION These results indicated that cyclooxygenation and 5 lipoxygenation inhibit the expression of iNOS in glomeruli of rats with NSN.