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Apelin-13對高血壓性腎纖維化的影響及機(jī)制研究

發(fā)布時(shí)間:2018-08-28 16:10
【摘要】:目的探討血管緊張素受體AT1相關(guān)的受體蛋白(APJ)激動(dòng)劑Apelin-13對高血壓性腎纖維化的影響及其機(jī)制。方法 12周齡雄性自發(fā)性高血壓大鼠隨機(jī)分為對照組、1μg/(kg·d)Apelin-13組、10μg/(kg·d)Apelin-13組、100μg/(kg·d)Apelin-13組;Apelin-13通過尾靜脈給藥。測量大鼠24 h尿蛋白量、血清肌酐和尿素氮濃度。采用套尾法測量尾動(dòng)脈收縮壓,HE染色和Masson染色觀察大鼠腎臟組織學(xué)改變,Western blot檢測腎臟組織中自噬相關(guān)蛋白微管相關(guān)蛋白1輕鏈3(LC3)、Beclin-1和p62的表達(dá)。結(jié)果與對照組比較,10μg/(kg·d)Apelin-13組、100μg/(kg·d)Apelin-13組以劑量依賴方式降低大鼠收縮壓、24 h尿蛋白量、血清肌酐和尿素氮水平、腎臟損傷評分和膠原容積分?jǐn)?shù)(均P0.05),減輕腎小管上皮細(xì)胞水腫,減少間質(zhì)膠原沉積,降低腎間質(zhì)纖維化程度。10μg/(kg·d)Apelin-13組、100μg/(kg·d)Apelin-13組也以劑量依賴方式增加大鼠腎臟組織中LC3-Ⅱ表達(dá)和LC3-Ⅱ/LC3-Ⅰ比值及Beclin-1表達(dá),降低p62表達(dá)(均P0.05)。結(jié)論 Apelin-13抑制高血壓性腎纖維化的進(jìn)展,其機(jī)制可能與Apelin-13抑制細(xì)胞自噬有關(guān)。
[Abstract]:Objective to investigate the effect and mechanism of angiotensin receptor AT1 associated receptor protein (APJ) agonist Apelin-13 on hypertensive renal fibrosis. Methods 12-week-old male spontaneously hypertensive rats were randomly divided into 1 渭 g / (kg d) Apelin-13 group and 10 渭 g / (kg d) Apelin-13 group. Apelin-13 was administered via tail vein. Urine protein, serum creatinine and urea nitrogen were measured in 24 h rats. The changes of renal histology in rats were observed by HE staining and Masson staining. The expression of autophagy associated protein microtubule-associated protein 1 (LC3), light chain 3 (LC3), Beclin-1 and p62 in renal tissue was detected by Western blot. Results compared with the control group, 10 渭 g / (kg d) Apelin-13 group (100 渭 g / (kg d) Apelin-13) decreased in a dose-dependent manner the levels of urinary protein, serum creatinine and urea nitrogen, renal injury score and collagen volume fraction (P0.05), and alleviated the edema of renal tubular epithelial cells in a dose-dependent manner. The expression of LC3- 鈪,

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