以口服3-胺基苯甲醯胺(3-Aminobenzamide)探討由脂多醣體(Lipopolysaccharide)所誘發C57鼠腎病變之發炎反應

Abstract

將C57鼠每日由腹腔注射脂多醣體(lipopolysaccharide，LPS，120μg/25g C57鼠)，連續注射14日，以建立由LPS所誘發C57鼠腎病變動物模式。經脂多醣體誘發C57鼠腎病變後，然後以3-胺基苯甲醯胺(3-aminobenzamide，3-AB，2.5 mg/25g C57鼠)口服給藥，連續16日後，發現腎病變鼠的尿蛋白，血清中肌酸酐、亞硝酸鹽/硝酸鹽(Nitrite / Nitrate)含量漸漸降低。C57鼠腎病變的腎清除功能亦恢復了近百分之九十。由脂多醣體誘發C57鼠腎病變的經3-胺基苯甲醯胺口服治療16日後，該C57鼠血清中腫瘤壞死因子(Tumor Necrosis Factor-α，TNF-α)、介白素(Interleukin-1β，IL-1β)及前列腺素E2 (Prostaglandinas E2，PGE2)含量也明顯降低。 同時，病理檢查也顯示以口服3-胺基苯甲醯胺治療後的該C57鼠腎病變之腎組織，其髓過氧化物活性(Myeloperoxidase，MPO)也下降，一氧化氮合成(nitric oxide synthase，NOS)及環氧(Cyclooxygenase-2， COX-2)的表現也顯著降低。腎病變C57鼠的腎組織顯著減緩了腎病變期中腎絲球變大、膈細胞的增生。 總結，口服3-胺基苯甲醯胺治療可明顯改善由脂多醣體所誘發C57鼠腎組織病變及腎功能衰退，其機轉可能是經由降低腎病組織一氧化氮合成及環氧(COX-2)的表現並降低發炎性細胞激素(cytokine)的生成而達成。

To study the nephritis in mouse model, each of the C57 mouse was first injected with 120 μg lipopolysaccharide (LPS) intraperitoneally for 14 days. The abnormally higher urine protein content and serum creatinine level typical of nephritic manifestations were detected and maintained for at least 16 days after termination of LPS treatment in all LPS-induced nephritic C57 mice. These high levels of urine protein, nitrite/nitrate, serum creatinine, serum PGE2, serum IL-1β, and TNF-α of LPS-induced nephritic syndrome in C57 mice were gradually decreased following oral treatment with 3-aminobenzamide (3-AB, 2.5mg/mouse) for 16 days. Concurrently, activities of myeloperoxidase(MPO), nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) from extracts of LPS-induced nephritic kidneys were also decreased based on the MPO and SDS-PAGE evaluation, as well as 90% recovery of kidney’s clearance function. Considering all the experimental evidences found in this study, the lessening effect of antioxidant 3-AB on the severity of LPS-induced nephritic in C57 mice, was most likely coming from its ability to reduce the expression of NOS and COX-2.