Zhang Yuan-Yuan, Jin Pei-Pei, Guo Deng-Zhou, Bian Dong
Graduate School, Hebei University of Chinese Medicine, Hebei, Shijiazhuang, 050000, China.
Hebei Yiling Hospital, Hebei, Shijiazhuang, 050000, China.
Heliyon. 2024 May 15;10(10):e31265. doi: 10.1016/j.heliyon.2024.e31265. eCollection 2024 May 30.
Tubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression.
We used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators.
Ade treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen.
OS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.
肾小管间质纤维化（TIF）是慢性肾衰竭（CRF）的关键病理特征，肾近端小管上皮细胞中的氧化应激（OS）和缺氧反应在疾病进展中起关键作用。本研究探讨了真武汤加味（MZWT）对这些过程的影响，旨在揭示其延缓CRF进展的潜在机制。
我们用腺嘌呤（Ade）诱导大鼠发生CRF，然后用盐酸贝那普利（洛汀新）和MZWT治疗8周。评估包括肝肾功能、电解质、血脂、肾组织病理学、OS水平、缺氧诱导因子（HIF）通路、炎症标志物及其他相关指标。在体外，将人肾皮质近端小管上皮细胞置于缺氧和脂多糖环境中72小时，同时用MZWT、FM19G11和N-乙酰-L-半胱氨酸进行处理。检测指标包括活性氧（ROS）、HIF通路活性、炎症标志物及其他相关指标。
Ade处理导致大鼠肾功能、血脂、电解质及肾小管间质结构显著破坏，同时伴有OS升高、HIF通路激活及炎症反应。在体内，MZWT有效改善了蛋白尿、肾功能不全、脂质和电解质失衡以及肾组织损伤；还抑制了OS、HIF通路激活、近端小管上皮细胞的上皮-间质转化（EMT），并减少了炎性细胞因子和胶原纤维的产生。体外研究结果表明，MZWT减少了近端小管上皮细胞的凋亡，降低了ROS生成，抑制了OS、HIF通路激活和EMT，并减少了炎性细胞因子和胶原的输出。
OS和缺氧反应对TIF的发展有显著影响。MZWT减轻了肾近端小管上皮细胞中的这些反应，从而延缓了CRF的进展。
