Guan Yue, Wu Xiao-Xiao, Duan Jia-Lin, Yin Ying, Guo Chao, Wei Guo, Wang Yan-Hua, Zhu Yan-Rong, Weng Yan, Xi Miao-Miao, Wen Ai-Dong
1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.
Am J Chin Med. 2015;43(7):1381-400. doi: 10.1142/S0192415X15500780. Epub 2015 Oct 27.
Traditional Chinese medicine (TCM) plays a systemic role in disease treatment, targeting multiple etiological factors simultaneously. Based on clinical experience, rhubarb and Salvia miltiorrhiza are commonly prescribed together for the treatment of chronic kidney disease (CKD) and have been proven to be very effective. However, the rationale of the combination remains unclear. The major active ingredients of these two herbs are rhein (RH) and danshensu (DSS), respectively. The aim of this paper is to investigate the renoprotective effects of RH and DSS in vitro and in vivo, and the underlying mechanism. A total of 5/6 nephrectomy rats and HK-2 cells were subjected to chronic renal injury. The combination of RH and DSS conferred a protective effect, as shown by a significant improvement in the renal function, blood supply, and fibrotic degree. Proinflammatory cytokines and adhesion molecules were suppressed by RH and DSS through NK-κB signaling. The combination also inhibited apoptosis by up-regulating Bcl-2 and down-regulating Bax. Inhibiting the TGF-β/Smad3 pathway was at least in part involved in the antifibrotic mechanism of the combination treatment of RH and DSS. This study demonstrates for the first time the renoprotective effect and the mechanism of RH and DSS combination on chronic renal injury. It could provide experimental evidence to support the rationality of the combinatorial use of TCM in clinical practices.
传统中医（TCM）在疾病治疗中发挥着系统性作用，可同时针对多种病因。基于临床经验，大黄和丹参常用于联合治疗慢性肾脏病（CKD），且已被证明非常有效。然而，这种联合用药的原理尚不清楚。这两种草药的主要活性成分分别是大黄酸（RH）和丹参素（DSS）。本文旨在研究RH和DSS在体外和体内的肾脏保护作用及其潜在机制。总共对5/6肾切除大鼠和HK-2细胞进行慢性肾损伤实验。RH和DSS联合用药具有保护作用，表现为肾功能、血液供应和纤维化程度显著改善。RH和DSS通过NF-κB信号通路抑制促炎细胞因子和黏附分子。联合用药还通过上调Bcl-2和下调Bax来抑制细胞凋亡。抑制TGF-β/Smad3信号通路至少部分参与了RH和DSS联合治疗的抗纤维化机制。本研究首次证明了RH和DSS联合用药对慢性肾损伤的肾脏保护作用及其机制。它可为支持中医临床联合用药合理性提供实验依据。
