陳永銘2006-07-262018-07-112006-07-262018-07-112003http://ntur.lib.ntu.edu.tw//handle/246246/23608背景：Fractalkine 可以促進腎小球疾病中單核球的侵潤和聚集。本研究探 fractalkine 在實驗型 anti-Thy1 腎小球腎炎的時序性表現，以及阻斷fractalkine 系統對anti-Thy1 腎小球腎炎的療效。 方法： 大鼠 anti-Thy1 腎小球腎炎的誘發方式同吾人先前報告。 實驗動物分 成三大組， A 組接受每日 PBS 靜注治療 (days 1-5)， B 組接受每日 PBS 靜 注治療 (days 1-2) 和商業用polyclonal rabbit anti-rat fractalkine 抗體 (days 3- 5)， C 組接受每日 polyclonal rabbit anti-rat fractalkine 抗體 (days 1-5)。 動物在第五日殺死，分別觀察蛋白尿 (BioRad 方法)，腎小球硬化 (H&E 染色)， 發炎細胞浸潤 (免疫組化染色)，以及腎小球基質蛋白的基因表現程度 (北方和 西方墨點染色)。腎小球內 fractalkine mRNA 以北方墨點染色檢查，尿液和腎小 球內的 fractalkine 蛋白則以西方墨點染色偵測。 結果：A 組大鼠在第五天呈顯著蛋白尿排泄，同時可見明顯的腎小球硬化，發 炎細胞浸潤，以及腎小球基質蛋白 (type 1 and 3 collagen 和 fibronectin) 的基因表現。 此外，A 組大鼠在第三至五天可觀察到腎小球內有 fractalkine 的基因 和蛋白表現增加，且尿液中亦有游離型 fractalkine 的排泄。 然而， 無論是 B或 C 組動物，施打商業用 anti-fractalkine 抗體後並不能減輕腎炎大鼠之蛋白 尿排泄、腎小球硬化、發炎細胞浸潤、或基質蛋白的基因表現。 結論：使用商業用 polyclonal rabbit anti-rat fractalkine 抗體並不能減緩大鼠 anti-Thy1 腎小球腎炎的嚴重度。Background. Fractalkine is a CX3C chemokine for mononuclear cells that has been implicated in the recruitment and accumulation of monocytes seen in glomerular diseases. This study investigated the sequential expression of fractalkine in rat anti-Thy1 nephritis, and the effect of fractakine blockade on the severity of anti-Thy1 nephritis. Methods. Rat anti-Thy1 glomerulonephritis was induced as described previously. Group A rats received monoclonal anti-Thy1 antibodies and daily 1X PBS injection; group B rats received monoclonal anti-Thy1 antibodies and daily 1X PBS injection (days 1-2) and rabbit anti-rat fractalkine injection (days 3-5); group C rats received monoclonal anti-Thy1 antibodies and daily rabbit anti-rat fractalkine injection (days 1-5). Fractalkine mRNA and protein were analyzed by Northern and Western blotting. Renal histomorphology was examined by H&E staining, glomerular macrophage and T cell infiltration were studied by immunohistochemical staining. Results. Group A rats showed an appreciable increase in urinary protein excretion, glomerulosclerosis, and matrix gene expression at days 5 of the nephritis, when compared with normal control rats. In addition, the nephritic rats showed an increase in glomerular fractalkine gene expression during days 1 to 5 of the disease. A parallel in crease in glomerular fractalkine protein expression was also seen during days 3 to 5. Urinary fractalkine excretion could be seen during days 3 to 5 of the nephritis. The administration of rabbit anti-rat fractalkine antibodies, whether between days 3 and 5 (group B), or during days 1 and 5 (group C), did not affect the severity of the nephritis. Conclusion. The present data shows that fractalkine is upregulated during the course of anti-Thy1 nephritis. However, blocking fractalkine activity with a commercially-available polyclonal antibody did not ameliorate the severity of the disease.application/pdf31437 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23608/1/912314B002335.pdf