Wu Junbiao, Liu Bihao, Liang Chunling, Ouyang Hui, Lin Jin, Zhong Yanchun, He Yu, Zhou Jie, Zhou Yuan, Zhou Jiuyao
Department of Pharmacy, the Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China.
Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Int Immunopharmacol. 2016 Apr;33:33-41. doi: 10.1016/j.intimp.2016.01.008. Epub 2016 Feb 4.
Zhen-wu-tang (ZWT), a traditional Chinese compound formula recorded in the Treatise on Febrile Diseases, has significant inhibitory effects on inflammatory damage and oxidative lesions in rats, but its mechanism of action remains unclear. The aim of the present study was to explore whether the anti-inflammatory and anti-oxidative effects of ZWT were mediated by the AGEs/RAGE/NF-κB signaling pathway in rats with cationic bovine serum albumin (C-BSA)-induced membranous glomerulonephritis (MGN). We found that ZWT significantly reduced the production of malondialdehyde (MDA), but enhanced the superoxide dismutase (SOD) activity. The ELISA results showed that ZWT not only reduced the serum levels of AGEs but also decreased the release of inflammatory mediators (TNF-α, IL-1β, and IL-6). Meanwhile, HE staining showed that pathological kidney injury was alleviated by ZWT. In addition, ZWT suppressed the expression of RAGE1 and NF-κB p65, as well as the nuclear translocation of NF-κB p65. The accumulation of AGEs, oxidative lesions and inflammation damage were reduced by an AGE inhibitor. Thus, the present study demonstrates that AGEs play a role in the pathogenesis of MGN and that AGE inhibition could reduce the inflammatory reactions and oxidative lesions in MGN. In general, ZWT attenuated MGN, in part, by inhibiting the AGEs/RAGE/NF-κB pathway.
真武汤(ZWT)是《伤寒论》中记载的一首传统中药复方,对大鼠的炎症损伤和氧化损伤具有显著的抑制作用,但其作用机制尚不清楚。本研究旨在探讨真武汤的抗炎和抗氧化作用是否通过阳离子牛血清白蛋白(C-BSA)诱导的膜性肾小球肾炎(MGN)大鼠的晚期糖基化终末产物(AGEs)/晚期糖基化终末产物受体(RAGE)/核因子κB(NF-κB)信号通路介导。我们发现,真武汤显著降低了丙二醛(MDA)的产生,但增强了超氧化物歧化酶(SOD)的活性。酶联免疫吸附测定(ELISA)结果表明,真武汤不仅降低了血清AGEs水平,还减少了炎症介质(肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6)的释放。同时,苏木精-伊红(HE)染色显示,真武汤减轻了肾脏病理损伤。此外,真武汤抑制了RAGE1和NF-κB p65的表达,以及NF-κB p65的核转位。AGEs抑制剂减少了AGEs的积累、氧化损伤和炎症损伤。因此,本研究表明,AGEs在MGN的发病机制中起作用,抑制AGEs可减少MGN中的炎症反应和氧化损伤。总体而言,真武汤部分通过抑制AGEs/RAGE/NF-κB途径减轻了MGN。