蓮蓬萃取物降低尿酸導致腎損傷之體內與體外研究

慢性腎臟病全球盛行率逐年增加，其致病機轉與尿酸堆積所引起發炎反應具有其相關性。蓮蓬萃取物 (lotus seedpod extract, LSE) 富含多酚類物質，實驗室過去研究發現LSE能有效抑制由脂多糖 (lipopolysaccharide) 引起的之發炎反應。但是對於LSE是否能抑制尿酸引起腎臟發炎的詳細機制仍未知。本研究將以動物和細胞實驗探討LSE是否具可抑制尿酸引發的腎臟發炎及詳細機制。首先動物實驗我們以adenine誘導大鼠腎損傷模式並餵食2% LSE，結果發現LSE組腎功能指標 (BUN、Cre、尿蛋白) 皆比adenine誘導組有下降的情形，並在病理切片中觀察到LSE組能減少腎絲球萎縮及腎臟纖維化的現象。進一步分析發現，LSE組能降低促發炎細胞激素 (TNF-α、IL-1、IL-6) 的分泌量與NF-κB相關蛋白表現。此外LSE組可增加抗氧化酵素 (SOD、GSH、GPx、CAT) 的活性與Nrf-2蛋白表現，並減少NOX-4蛋白的表現。細胞實驗使用尿酸刺激NRK-52E細胞並加入LSE進行分析。結果發現LSE能降低尿酸引發的ROS與促發炎因子，並降低NF-κB相關發炎路徑蛋白表現。同時LSE也增加了抗氧酵素及Nrf-2蛋白表現量，減少NOX-4蛋白表現量，結果皆與動物實驗一致。本實驗經由動物及細胞實驗證實LSE可透過增加抗氧化酵素及降低發炎反應減緩尿酸導致腎損傷，未來可應用於改善慢性腎臟疾病。

Overproduction of uric acid (UA) and reduced renal excretion led to hyperuricemia, which is a risk factor for the development of chronic kidney disease (CKD). High UA levels promote renal tubule cell injury by oxidative stress and inflammation. It has been proved that lotus seedpod, a traditional Chinese herbal medicine, has antioxidant, anti-aging, anti-glycative and anti-inflammatory properties. The current study aimed to assess the possible protective effects of lotus seedpod extract (LSE) against hyperuricemia-induced CKD. In vivo, adenine-induced CKD was significantly ameliorated in LSE-fed rats as gauged by inhibition of serum levels of biochemical markers of kidney damage and the secretion of albumin to urine. LSE supplementation significantly alleviated CKD development, which may result from inhibiting adenine-mediated renal inflammation with the increases in activities of antioxidant enzymes. In vitro, renal tubular epithelial cells NRK-52E pretreated with UA were demonstrated to trigger viability loss, induction of oxidative stress and occurrence of apoptosis. Non-cytotoxic doses of LSE abolished the UA-induced cell injury and the production of reactive oxygen species (ROS). Moreover, LSE exhibited the antioxidant and anti-inflammatory effects on the UA-treated cells via modulation of the nuclear factor erythroid 2-related factor 2 (Nrf-2) activation and nuclear factor kappa B (NF-κB) pathway, respectively. These findings imply that LSE reduces renal tubular epithelial cell injury and inflammation in the hyperuricemia-induced CKD, and provides a new mechanism for its nephroprotective activity.