Tang Zhongfu, Huang Chuanbing, Li Ming, Cheng Lili, Chen Junjie, Shang Shuangshuang, Liu Sidi
First Affiliated Hospital of Anhui University of Chinese Medicine.
Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Hefei 230031, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Aug 20;45(8):1625-1632. doi: 10.12122/j.issn.1673-4254.2025.08.07.
To investigate the mechanism of (QJZ) for ameliorating renal damage in MRL/lpr mice.
With 6 female C57BL/6 mice as the normal control group, 30 female MRL/lpr mice were randomized into model group, QJZ treatment groups at low, moderate and high doses, and prednisone treatment group (6). After 8 weeks of treatment, the mice were examined for 24-h urine protein, creatinine and albumin levels, serum levels of IgG, complement 3 (C3), C4, anti-dsDNA, interferon γ (IFN‑γ) and interleukin 17 (IL-17). Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy (TEM). The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR, Western blotting and immunohistochemistry.
Compared with those in the model group, the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG, anti-dsDNA, IFN‑γ and IL-17 levels and elevation of serum C3 and C4 levels. HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups. TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups. QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88, NF-κB, p65 and p52 in the mouse models.
QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.
探讨芪甲蛭(QJZ)改善MRL/lpr小鼠肾损伤的机制。
以6只雌性C57BL/6小鼠作为正常对照组,将30只雌性MRL/lpr小鼠随机分为模型组、芪甲蛭低、中、高剂量治疗组及泼尼松治疗组(每组6只)。治疗8周后,检测小鼠24小时尿蛋白、肌酐和白蛋白水平,血清免疫球蛋白G(IgG)、补体3(C3)、C4、抗双链DNA(anti-dsDNA)、干扰素γ(IFN-γ)和白细胞介素17(IL-17)水平。取肾组织进行苏木精-伊红(HE)染色组织病理学检查,并用透射电子显微镜(TEM)观察肾小球超微结构变化。采用逆转录定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法(Western blotting)和免疫组织化学法检测肾组织中髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路相关分子的表达。
与模型组相比,芪甲蛭3个剂量组及泼尼松治疗组小鼠的肾损伤生物标志物及血清IgG、anti-dsDNA、IFN-γ和IL-17水平显著降低,血清C3和C4水平升高。HE染色显示,各治疗组肾小球内皮细胞增殖减轻,系膜增厚减轻。TEM观察进一步显示,干预组肾小球内电子致密沉积物减少,炎性细胞浸润减少。芪甲蛭3个剂量组及泼尼松治疗均显著降低小鼠模型肾组织中MyD88、NF-κB、p65和p52的表达水平。
芪甲蛭可能通过抑制MyD88/NF-κB信号通路的过度激活来改善MRL/lpr小鼠的肾损伤。