Yang Xueling, Luo Qinglin, Wu Zhifen, Wang Chunxuan, Yang Yuanjing, Zheng Luquan, Li Ke, Zhao Lei, Jurong Yang
Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Core Research Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Pharm Biol. 2025 Dec;63(1):364-373. doi: 10.1080/13880209.2025.2498166. Epub 2025 May 7.
Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb , is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.
This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.
Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.
Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.
Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.
丹参酮IIA（Tan IIA）是一种源自传统中草药的生物活性化合物，因其在各种肾脏疾病中的保护作用而闻名。然而，其在梗阻性肾病中的作用尚未得到充分研究。
本研究旨在探讨丹参酮IIA在单侧输尿管梗阻（UUO）小鼠模型中的保护作用，并阐明其作用的细胞和分子机制。
对Gasdermin D（GSDMD）基因敲除小鼠及其野生型（WT）同窝小鼠进行UUO手术，术前24小时给予丹参酮IIA治疗。用转化生长因子-β1（TGF-β1，50 ng/mL处理24小时）处理人近端肾小管上皮细胞（HK-2细胞）以诱导纤维化，随后再用丹参酮IIA（5 μM）处理3小时。
丹参酮IIA显著降低了UUO小鼠细胞外基质（ECM）成分的表达，包括I型胶原、α平滑肌肌动蛋白（α-SMA）、波形蛋白和纤连蛋白。丹参酮IIA减轻了GSDMD介导的细胞焦亡。然而，在接受UUO手术的GSDMD基因敲除小鼠中，丹参酮IIA对ECM基因表达和肾小管间质胶原沉积的保护作用减弱。研究表明，丹参酮IIA降低了HK-2细胞中GSDMD的激活和纤连蛋白的蛋白表达。
丹参酮IIA可能减轻肾小管上皮细胞（RTECs）中GSDMD介导的细胞焦亡并减少肾纤维化，凸显了其作为预防输尿管梗阻后肾脏疾病进展的治疗策略的潜力。
