Huijuan Wang, Xiaoxu Chen, Rui Song, Xinghui Li, Beibei Tao, Jianchun Mao
Shanghai University of Traditional Chinese Medicine, Longhua Hospital, China.
Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China.
Biomed Pharmacother. 2017 Jul;91:358-365. doi: 10.1016/j.biopha.2017.04.031. Epub 2017 May 2.
Hyperuricemia is associated with the development of chronic kidney disease. Epithelial-to-mesenchymal transition (EMT) induced by hyperuricemia is blamed for initiation of renal fibrosis, which is one of the main characters of hyperuricemic nephropathy. Qi-Zhu-Xie-Zhuo-Fang (QZXZF) has been employed clinically for many years to treat patients with hyperuricemic nephropathy, but the mechanism underlying the therapeutic potential remains unclear. In the present study, QZXZF was applied to rats treated with adenine (100mg/kg) and potassium oxonate (300mg/kg) and biochemical estimations, morphology and immunohistochemistry were performed to investigate whether QZXZF can improve hyperuricemia induced renal fibrosis and to explore the possible mechanisms. We found QZXZF significantly reduced serum uric acid, cystatinC and hepatic xanthine oxidase (XO) activities, meanwhile improved renal histopathologic changes of hyperuricemic nephropathy rats. Furthermore, QZXZF not only substantially decreased the protein levels of fibronectin and Collagen I but also downregulated E-cadherin and upregulated α-SMA in the kidneys of hyperuricemic nephropathy rats. In conclusion, QZXZF reduced serum uric acid levels and protected kidney against fibrosis in potassium oxonate and adenine induced hyperuricemic nephropathy rats. The mechanism might be associated with the inhibition of hepatic XO activity and the renal epithelial-to-mesenchymal transition.
高尿酸血症与慢性肾脏病的发生发展相关。高尿酸血症诱导的上皮-间质转化（EMT）被认为是肾纤维化起始的原因，而肾纤维化是高尿酸血症肾病的主要特征之一。芪术泄浊方（QZXZF）已在临床上应用多年来治疗高尿酸血症肾病患者，但其治疗潜力背后的机制仍不清楚。在本研究中，将芪术泄浊方应用于用腺嘌呤（100mg/kg）和氧嗪酸钾（300mg/kg）处理的大鼠，并进行生化评估、形态学和免疫组织化学检查，以研究芪术泄浊方是否能改善高尿酸血症诱导的肾纤维化并探索可能的机制。我们发现芪术泄浊方显著降低血清尿酸、胱抑素C和肝脏黄嘌呤氧化酶（XO）活性，同时改善高尿酸血症肾病大鼠的肾脏组织病理学变化。此外，芪术泄浊方不仅显著降低高尿酸血症肾病大鼠肾脏中纤连蛋白和I型胶原的蛋白水平，还下调E-钙黏蛋白并上调α-平滑肌肌动蛋白。总之，芪术泄浊方降低血清尿酸水平，并在氧嗪酸钾和腺嘌呤诱导的高尿酸血症肾病大鼠中保护肾脏免受纤维化。其机制可能与抑制肝脏XO活性和肾脏上皮-间质转化有关。
