系膜增殖性肾炎中血栓素及白三烯对肾小球血液动力学的影响

Effects of thromboxane and leukotriene on glomerular hemodynamics in mesangioproliferative nephritis

在抗Ｔｈｙ１．１抗体所致的大鼠系膜增殖性肾炎中，测定了白细胞衍生的血栓素（ＴＸ）及白三烯（ＬＴ）对肾小球血液动力学的作用。在肾炎鼠，肾小球超滤系数（Ｋｆ）、肾小球滤过率（ＧＦＲ）及肾血流量（ＲＢＦ）的急性降低伴有肾小球白细胞计数的升高及肾小球ＴＸＢ＿２、ＬＴＢ＿４的合成增多。白细胞除去可抑制ＴＸＢ＿２及ＬＴＢ＿４的合成并完全防止ＧＦＲ及ＲＢＦ的降低。合用ＴＸ合成酶抑制剂及花生四烯酸５－脂氧化酶抑制剂也防止了ＧＦＲ及ＲＢＦ的下降。分别应用ＴＸ合成酶或５－脂氧化酶抑制剂仅可部分防止ＧＦＲ及ＲＢＦ的降低。ＴＸ受体拮抗剂或５－脂氧化酶抑制剂可防止Ｋｆ的减少。这些资料说明浸润于肾小球的白细胞所衍生的ＴＸ、ＬＴ参与系膜增殖性肾炎模型的急性肾功能减退。

The role of leukocyte-derived thromboxane(TX)and leukotriene(LT)on renal and glomerular hemodynamics was investigated in rat mesangioproliferative nephritis induced by anti-Thy 1 antibodies. In nephritic ratst, acute decrements in glo-merular ultrafiltration coefficient (Kf), glomerular filtration rate(GFR) and renal blood flow (RBF) were associated with increments in glomerular leukocyte counts and in the glomerular synthesis of TXB-2 and LTB-4. Leukocyte depletion eliminated the enhanced synthesis of TXB-2 and LTB-4,blocked the decrements in GFR and RBF.Likewise,com-bined pretreatment of rats with TX synthetase inhibitor and an arachidonate 5-lipoxy-genase inhibitor blocked the decrements in GFR and RBF.Selective inhibition of TX syn-thetase or 5-lipoxygenase only partially ameliorated the decrements in GFR and RBF. Antagonism of TX receptor or inhibition of 5-lipoxygenase also inhibited the decrement in Kf.These data indicate that glomerular infiltrating leukocyte-derived TX and LT mediate the acute renal dysfunction in mesangioproliferative nephritis.