腎血管障害を伴う実験的糸球体疾患における血管作動物質の生理学的役割

Physiological Role of Vaso-operating Substances in Experimental Glomerular Disease with Renal Angiopathy

　血管障害を伴う糸球体疾患におけるET−1,PGI₂，TXA₂の腎血管壁での産生動態と病態の進展に対する影響を検討するため，PAN投与によるFGSラット24匹を作製し投与後30,60,90日目に屠殺した．分離した腎血管内皮細胞からのET−1産生量は腎機能の低下をみる前に著増し，実験期間中持続した．TXA₂量も漸増し組織像の悪化が並行して認められた．ET−1の産生量はPANによる微小な血行動態変化を反映して増加するものと考えられ，同時にET−1による血管平滑筋細胞の増殖は，TXA₂産生量を増加させ病態の悪化に関与する可能性が示唆された．PGI₂量は顕著な変化は認められなかったが，エイコサノイド代謝系のうちTXA₂の合成経路のみが促進されたためかもしれない．したがって，血管壁構成細胞からのET−1,PGI₂，TXA₂産生量の病態の解明や早期把握が期待できる．

In order to investigate the production patterns in vascular walls of ET-1, PGI₂ and TXA₂ and their effects on the progress of glomerular disease associated with angiopathy, FGS rats were prepared by PAN administration and sacrificed at 30, 60 and 90 days after administration. The amount of production of ET-1 from component cells of isolated vascular walls in-creased by 7.2 times prior to reduction of renal function. The amount of TXA₂, also gradually increased along with the exacerbation of histological findings. It seems that the increasing amount of production of ET-1 reflects the change of blood flow after PAN administra-tion, and the proliferation of vascular smooth muscle cells promotes the TXA₂, production, which possibly aggravates the disease.

Although there was no apparent change in the amount of PGI₂, it was supposed that this was due to the acceleration of the TXA₂ synthetic passway in the metabolic system of eicosanoid. Therefore, assays of production amounts of ET-1, PGI₂, TXA₂, from isolated cells may be useful for elucidation of disease state and early recognition of renal disease associated with vari-ous angiopathies.