目的 评价真武汤对系膜增生性肾小球肾炎（MsPGN）的保护作用，并探讨其抑制系膜细胞异常增殖及炎症反应的作用机制。方法 小鼠适应性饲养1周后，随机分为对照组、模型组、泼尼松（7.5 g·kg^-1）组和真武汤低、中、高剂量（3.2、6.3、12.6 g·kg^-1，以生药剂量计）组，除对照组外，采用阳离子牛血清白蛋白建立MsPGN小鼠模型，模型建立完成后次日开始ig给药，每天1次，连续2周，对照组及模型组给予等体积0.9%氯化钠溶液。通过检测24 h尿蛋白、血清肌酐（Cr）、尿素氮（BUN）及肾小球滤过率（GFR）评价肾功能；苏木素-伊红（HE）、糖原（PAS）染色观察肾组织病理变化，免疫组化检测Ki67及增殖细胞核抗原（PCNA）表达，免疫荧光检测F4/80及Ly6G阳性炎症细胞浸润。体外采用脂多糖诱导系膜细胞炎症增殖模型，用2.5%、5.0%、7.5%真武汤含药血清干预，采用CCK-8法检测细胞增殖，流式细胞术检测细胞周期及凋亡，实时荧光定量PCR（qRT-PCR）检测炎症因子表达。Western blotting实验检测RhoA、Rho相关卷曲螺旋蛋白激酶（ROCK）、肌球蛋白轻链（MLC）及p-MLC蛋白表达。通过分子对接及生物膜干涉技术（BLI）验证真武汤核心成分与RhoA蛋白的相互作用。结果 与模型组比较，真武汤干预可显著降低MsPGN小鼠24 h尿蛋白、Cr及BUN水平（P＜0.01），提高GFR（P＜0.01），明显改善肾小球系膜增生及肾组织病理损伤。免疫组化结果显示真武汤可显著降低Ki67及PCNA表达（P＜0.01）。免疫荧光结果显示真武汤减少F4/80⁺巨噬细胞及Ly6G⁺中性粒细胞浸润（P＜0.01），qRT-PCR结果显示真武汤减少炎症因子表达。体外实验表明真武汤含药血清可显著抑制脂多糖诱导的系膜细胞增殖（P＜0.01），促进细胞凋亡（P＜0.01），并降低炎症因子表达（P＜0.01）。Western blotting结果显示真武汤可显著下调RhoA、ROCK及p-MLC蛋白表达（P＜0.05、0.01）。分子对接及BLI结果显示芍药苷及白术内酯III与RhoA蛋白具有良好的结合活性。结论 真武汤可抑制系膜细胞异常增殖及炎症反应，从而改善MsPGN，其作用可能与芍药苷及白术内酯III与RhoA蛋白结合，进而参与RhoA/ROCK/MLC信号通路调控相关。

Objective To evaluate the protective effects of Zhenwu Decoction on mesangial proliferative glomerulonephritis (MsPGN) and to investigate its mechanisms in regulating mesangial cell proliferation and inflammatory responses as well as it s material basis. Methods After one week of adaptive feeding, the mice were randomly divided into a control group, a model group, a prednisone (7.5 g·kg^-1) group, and low, medium, and high-dose Zhenwu Decoction (3.2, 6.3, 12.6 g·kg^-1, calculated as the raw drug dose) groups. Except for the control group, cationic bovine serum albumin was used to establish a MsPGN mouse model. The ig administration began the day after the model was established, once daily for 2 consecutive weeks. The control group and model group were given equal volumes of 0.9% sodium chloride solution. Renal function was evaluated by measuring 24 h urinary protein, serum creatinine (Cr), blood urea nitrogen (BUN), and glomerular filtration rate (GFR). Renal pathological changes were observed by HE and PAS staining. Immunohistochemistry was performed to detect Ki-67 and PCNA expression. Immunofluorescence was used to evaluate infiltration of F4/80 and Ly6G positive inflammatory cells. In vitro, lipopolysaccharide (LPS) was used to induce mesangial cell proliferation and inflammation, intervene with 2.5%, 5.0%, and 7.5% Zhenwu Decoction drug-containing serum, cell proliferation was assessed by CCK-8 assay, while cell cycle and apoptosis were analyzed by flow cytometry. Real-time quantitative PCR was used to detect inflammatory cytokines. Western blotting was performed to detect RhoA, ROCK, MLC and phosphorylated MLC (p-MLC). Molecular docking and biolayer interferometry (BLI) were used to verify the interaction between active components of Zhenwu Decoction and RhoA protein. Results Compared with the model group, Zhenwu Decoction significantly reduced 24 h urinary protein, Cr and BUN levels (P<0.01), increased GFR (P<0.01), and improved renal pathological injury. Zhenwu Decoction significantly decreased Ki-67 and PCNA expression (P<0.01). Immunofluorescence results showed reduced infiltration of F4/80⁺ macrophages and Ly6G⁺ neutrophils (P<0.01). In vitro experiments showed that Zhenwu Decoction-containing serum significantly inhibited LPS-induced mesangial cell proliferation (P<0.01), promoted apoptosis (P<0.01), and reduced TNF-α, IL^-1β, IL-6 and MCP-1 expression (P<0.01). Western blotting results showed that Zhenwu Decoction significantly downregulated RhoA, ROCK and p-MLC protein expression (P<0.05, 0.01). Molecular docking and BLI assays demonstrated good binding activity between paeoniflorin, atractylenolide III and RhoA protein. Conclusion Zhenwu Decoction can inhibit abnormal mesangial cell proliferation and inflammatory responses, thereby ameliorating MsPGN. Its effects may be associated with the regulation of the RhoA/ROCK/MLC signaling pathway, potentially through the interaction of paeoniflorin and atractylenolide III with RhoA protein.

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国家自然科学基金项目（82505159，82374130，82174061）；广东省自然科学基金项目（2026A1515011996）；广东省科协青年科技人才培育计划（SKXRC2025155）；全国中药特色技术传承人才培训项目（国中医药人教函［2023］ 96号）；深圳市医疗卫生三名工程项目（SZZYSM202111002）；深圳市基础研究面上项目（JCYJ20220531102208019）