Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing, China.
Exp Mol Pathol. 2011 Jun;90(3):287-94. doi: 10.1016/j.yexmp.2011.03.001. Epub 2011 Mar 5.
Apolipoprotein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the progression of glomerulosclerosis (GS). We conducted this investigation to explore whether all-trans retinoic acid (ATRA) could regulate the apoE expression in the pathological process of GS. 120 Wistar rats were divided into three groups at random: sham operation group (SHO), glomerulosclerosis model group without treatment (GS), GS model group treated with ATRA (GA); n=40, respectively. The disease of GS in rat was established by uninephrectomy and adriamycin (5mg/kg) injection. At the end of 9 and 13 weeks, 20 rats in each group were killed and the relevant samples were collected. 24-hour urine total protein (24UTP), 24-hour urine excretion for albumin (24Ualb), serum total protein (TP) and serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (Scr), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), serum and urine apoE and glomerulosclerosis index (GSI) were measured. The protein expressions of collagen IV (Col-IV), fibronectin (FN) and apoE in glomeruli were determined by immunohistochemistry. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to detect the expression of apoE mRNA in kidney. TP and Alb in GA group in 9/13-week were increased than those of GS group, however, the differences were not statistically significant. Compared with group GS at 9/13 weeks, values of 24UTP, 24Ualb, BUN, Scr, TC, TG, HDL, LDL, serum and urine apoE, and GSI in GA group that were significantly reduced, and protein expressions of Col-IV, FN and apoE in glomeruli and expression of apoE mRNA in renal tissue were significantly down-regulated by ATRA (P<0.01). In conclusion, ATRA can regulate the expression of apoE, reduce the accumulation of extracellular matrix (ECM) and step down the progression of GS.
载脂蛋白 E（apoE）是胆固醇稳态中的一种重要血浆蛋白，在肾小球硬化（GS）的进展中发挥关键作用。我们进行这项研究是为了探讨全反式视黄酸（ATRA）是否可以调节 GS 病理过程中的 apoE 表达。120 只 Wistar 大鼠随机分为三组：假手术组（SHO）、未治疗的肾小球硬化模型组（GS）和 ATRA 治疗的肾小球硬化模型组（GA）；每组 n=40。通过单侧肾切除术和阿霉素（5mg/kg）注射建立大鼠 GS 疾病。在第 9 周和第 13 周末，每组各有 20 只大鼠被处死并收集相关样本。测量 24 小时尿总蛋白（24UTP）、24 小时尿白蛋白排泄量（24Ualb）、血清总蛋白（TP）和血清白蛋白（Alb）、血尿素氮（BUN）、血清肌酐（Scr）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、血清和尿液 apoE 以及肾小球硬化指数（GSI）。通过免疫组织化学法测定肾小球中胶原 IV（Col-IV）、纤维连接蛋白（FN）和 apoE 的蛋白表达。实时逆转录聚合酶链反应（real-time RT-PCR）用于检测肾组织中 apoE mRNA 的表达。9/13 周时 GA 组的 TP 和 Alb 高于 GS 组，但差异无统计学意义。与 9/13 周时的 GS 组相比，GA 组的 24UTP、24Ualb、BUN、Scr、TC、TG、HDL、LDL、血清和尿液 apoE 以及 GSI 明显降低，肾小球中 Col-IV、FN 和 apoE 的蛋白表达以及肾组织中 apoE mRNA 的表达明显下调（P<0.01）。总之，ATRA 可调节 apoE 的表达，减少细胞外基质（ECM）的积累，并减缓 GS 的进展。
