Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Department of Anatomy, Anhui Medical University, Hefei, Anhui, China.
Life Sci. 2012 Oct 5;91(11-12):369-376. doi: 10.1016/j.lfs.2012.08.013. Epub 2012 Aug 15.
Uric acid nephropathy (UAN) is due to excessive uric acid, which leads to hyperuricemia and kidney damage via the deposition of urate microcrystals in the kidneys. Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from the traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). This study aimed to evaluate the anti-inflammatory and immunomodulatory effects of IGPS and its mechanism on UAN rats.
The experimental model of UAN rats was induced by using uricopoiesis promoter adenine and uricase inhibitor potassium oxonate (PO). Treatment groups received three different doses of IGPS, allopurinol (AP) and benzbromarone (BEN) daily for 24days respectively. The histopathology of renal tissues in UAN rats were assessed for conventional morphological evaluation. The nuclear factor-κBp65 (NF-κBp65), monocyte chemoattractant protein-1 (MCP-1) and α-smooth muscle actin (α-SMA) protein expression of renal tissues in UAN rats were investigated by immunohistochemistry. MCP-1 and α-SMA mRNA levels were monitored by method of reverse transcription polymerase chain reaction (RT-PCR).
Treatment with IGPS significantly ameliorated UAN induced renal tissue injury, inhibited the biological activity of NF-κBp65, MCP-1 and α-SMA, and suppressed the mRNA expressions of MCP-1 and α-SMA.
IGPS exerts a protective effect against renal injury in UAN rats, possesses anti-inflammatory and immunomodulatory effects by inactivating NF-κBp65 pathway transmembrane signal transduction, down regulating the expression of MCP-1 and α-SMA to modulate pro-inflammatory mediator production in nephropathy tissue to improve renal fibrosis in UAN rats.
尿酸肾病（UAN）是由于尿酸过多，通过尿酸微晶体在肾脏中的沉积，导致高尿酸血症和肾脏损伤。鸡矢藤（Paederia scandens）的环烯醚萜苷（IGPS）是从传统中药鸡矢藤（Rubiaceae）中分离得到的主要活性成分。本研究旨在评价 IGPS 对 UAN 大鼠的抗炎和免疫调节作用及其机制。
采用尿酸生成促进剂腺嘌呤和尿酸酶抑制剂氧嗪酸钾（PO）诱导 UAN 大鼠模型。治疗组分别给予三种不同剂量的 IGPS、别嘌醇（AP）和苯溴马隆（BEN），每日治疗 24 天。对 UAN 大鼠肾组织进行常规形态学评价。通过免疫组织化学法检测 UAN 大鼠肾组织核因子-κBp65（NF-κBp65）、单核细胞趋化蛋白-1（MCP-1）和α-平滑肌肌动蛋白（α-SMA）蛋白的表达。采用逆转录聚合酶链反应（RT-PCR）法检测 MCP-1 和 α-SMA mRNA 水平。
IGPS 治疗可显著改善 UAN 诱导的肾组织损伤，抑制 NF-κBp65、MCP-1 和 α-SMA 的生物学活性，并抑制 MCP-1 和 α-SMA 的 mRNA 表达。
IGPS 对 UAN 大鼠肾损伤具有保护作用，通过抑制 NF-κBp65 通路跨膜信号转导，下调 MCP-1 和 α-SMA 的表达，调节肾病组织中促炎介质的产生，从而发挥抗炎和免疫调节作用，改善 UAN 大鼠的肾纤维化。
