小鼠腎臟損傷下之尿中 D- 乳酸濃度與腎臟中乳酸轉運蛋白表現之探討
D- 乳酸和人類許多疾病有關，例如腦病、酸中毒、糖尿病等；尿中 D- 乳酸 含量與糖尿病大鼠腎病病程具有高度的相關性，可能可作為腎病變的指標。
另一方面，許多臨床及體外試驗證實，馬兜鈴酸可引起腎小管細胞受損，為 了研究尿中 D- 乳酸與腎損傷的關係，本研究選擇誘導馬兜鈴酸腎病變來探討 尿中 D- 乳酸含量的變化，並研究腎臟中 D- 乳酸轉運蛋白的表現，以了解 D- 乳酸在腎臟中再吸收機制與腎病的關連。
實驗動物為 C3H/He 雌鼠，以尾靜脈注射方式每天給予每公斤體重 10 毫克的 馬兜鈴酸、共給予 5 天藉以誘導腎損傷，並從尿蛋白、尿酶 N-acetyl-beta-D-g lucosaminidase （ NAG ）的觀察判斷腎功能。另外並利用西方轉漬法分析小 鼠腎均質液中的腎臟乳酸轉運蛋白 MCT 2 、 slc5a8 的表現量。結果發現，給 予馬兜鈴酸後，尿蛋白與 NAG 皆大量增加，顯示腎小管已受到破壞；而尿中 D- 乳酸含量是對照組的將近 40 倍（與尿中肌胺酸酐的比例分別是 311.31 ± 7 1.7 及 8.60 ± 1.80 μM/mM ）；小鼠腎臟乳酸轉運蛋白 MCT 2 及 slc5a8 的表 現量在給予馬兜鈴酸後則減少。
本研究證實尿中 D- 乳酸含量與馬兜鈴酸腎損傷具高度相關性，造成這種情形 的可能原因之ㄧ是因為腎臟乳酸轉運蛋白的表現改變，尿中 D- 乳酸或許可為 臨床上判斷腎病病程的指標之ㄧ。
The Study of the Urinary D-lactate Concentration and Lactate Transporters Expression in Mice Renal Injury
D-lactate is associated with some human diseases such as diabetes mellitus and encephalopath y, and urinary D-lactate may be used as an indicator to determine the level of kidney damage i n diabetic rats. Clinical and in vitro findings have previously suggested that the proximal tubul e was the target of aristolochic acid (AA). In this study, the mice model of AA-induced nephro pathy was used to investigate the relation between urinary D-lactate and renal injury.
The proximal tubular lesions were induced by intravenous injections of AA at a high dose of 1 0 mg/kg body weight/day for 5 days and were characterized biochemically. Urinary excretion of proteins, urinary N-acetyl-beta-D-glucosaminidase (NAG), and plasma creatinine was deter mined. Urinary D-lactate was separated by our proposed column-switching high-performance liquid chromatography (HPLC) method with fluorescence detection. The expressions of lactat e transporters, slc5a8 and MCT 2, in the proximal tubule of normal and AA treated mice kidne y were studied by western blot analysis.
