| 摘要: |
| [目的] 基于纤维肉瘤蛋白（Raf）/丝裂原活化的细胞外信号调节激酶（MEK）/细胞外信号调节激酶（ERK）通路探讨白芍总苷（TGP）对肾结石（KS）大鼠肾纤维化的影响。[方法] 将建模成功的 KS 大鼠分为 KS 组、TGP 低剂量（L-TGP）组、TGP 高剂量（H-TGP）组（灌胃 100、200 mg/kg 的 TGP），TGP+2-（[ 2-苯乙基）硫代]烟酸（ML-099）组（灌胃 200 mg/kg 的 TGP+腹腔注射 11.7 mg/kg ML-099）。每组 18 只，对照（Ctrl）组和 KS 组灌胃和腹腔注射等量生理盐水，每日 1 次，连续给药 28 d。检测各组大鼠肾功能；ELISA 试剂盒检测 KS 大鼠血清中白细胞介素（IL）-6、IL-1β的水平；冯库萨（Von-Kossa）染色观察肾组织内病理性钙沉积；苏木精-伊红（HE）和马松（Masson）染色检测肾组织病理学；免疫组化检测肾组织中转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）的水平；Western blot 检测肾组织中 Raf/MEK/ERK 通路蛋白的表达。[结果] Ctrl 组肾组织结构完整、未见明显的胶原纤维和草酸钙（CaOx）结晶体；KS 组肾组织结构混杂，肾小管扩张或变形，可见明显炎性细胞浸润、胶原纤维沉积和 CaOx 结晶体，胶原容积分数（CVF）和 CaOx 结晶评分升高；L-TGP、H-TGP 组肾组织病理损伤依次改善，胶原纤维沉积和 CaOx 结晶体依次减少，CVF 和 CaOx 结晶评分降低；TGP+ML-099 组肾组织损伤进一步加重，胶原纤维沉积和 CaOx 结晶体进一步增加，CVF 和 CaOx 结晶评分升高。KS 组尿素氮（BUN）、血肌酐（Scr）、24 h 尿蛋白、IL-6、IL-1β、TGF-β1、α-SMA、p-Raf/Raf、p-MEK/MEK、p-ERK/ERK 高于 Ctrl 组（P<0.05），L-TGP、H-TGP 组 BUN、Scr、24 h 尿蛋白、IL-6、IL-1β、TGF-β1、α-SMA、p-Raf/Raf、p-MEK/MEK、p-ERK/ERK 低于 KS 组（P<0.05）；TGP+ML-099 组 BUN、Scr、24 h 尿蛋白、IL-6、IL-1β、TGF-β1、α-SMA、p-Raf/Raf、p-MEK/MEK、p-ERK/ERK 高于 H-TGP 组（P<0.05）。[结论] TGP 可能通过抑制 Raf/MEK/ERK 通路，抑制炎症反应，改善 KS 大鼠的肾纤维化。 |
| 关键词: 纤维肉瘤蛋白 丝裂原活化的细胞外信号调节激酶 细胞外信号调节激酶 白芍总苷 肾结石 肾纤维化 |
| DOI：10.11656/j.issn.1672-1519.2026.10.12 |
| 分类号:R692.4 |
| 基金项目:河北省卫生健康委员会医学科学研究课题计划项目（20250853）。 |
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| Effects of total glucosides of paeony on renal fibrosis in rats with kidney stones based on Raf/MEK/ERK pathway |
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WANG Junhao, FENG Rui, LI Yongzhang, HAN Jianpeng, ZHANG Qian, DU Fei
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Department of Urology, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China
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| Abstract: |
| [Objective] To discuss the effect of total glucosides of paeony（TGP）on renal fibrosis in rats with kidney stones（KS）based on the rapidly accelerated fibrosarcoma（Raf）/mitogen-activated extracellular signal-regulated kinase（MEK）/extracellular regulated protein kinase（ERK）pathway. [Methods] The successfully modeled KS rats were separated into the KS group，the low-dose TGP（L-TGP）group，the high-dose TGP（H-TGP）group（gavage of 100 and 200 mg/kg TGP），and the TGP+2-（[2-phenylethyl）thio]nicotinic acid（ML-099）group（gavage of 200 mg/kg TGP+intraperitoneal injection of 11.7 mg/kg ML-099），with 18 rats per group. The Ctrl group and the KS group were administered the same amount of normal saline by gavage and intraperitoneal injection once a day for 28 consecutive days. The renal functions of rats in each group were detected. The levels of interleukin（IL）-6 and IL-1β in the serum of KS rats were detected by ELISA kits. Von-Kossa staining was used to observe pathological calcium deposition in renal tissue. Renal histopathology was measured by HE and Masson staining. The levels of transforming growth factor β1（TGF-β1）and α-smooth muscle actin（α-SMA）in renal tissue were detected by immunohistochemistry. The expression of Raf/MEK/ERK pathway proteins in renal tissue was measured by Western blot. [Results] The renal tissue structure in the Ctrl group was intact，and no obvious collagen fibers or CaOx crystals were observed. In the KS group，the renal tissue structure was mixed，the renal tubules were dilated or deformed，obvious inflammatory cell infiltration，collagen fiber deposition and CaOx crystals could be observed，and the CVF and CaOx crystal scores increased. The pathological damage of renal tissues in the L-TGP and H-TGP groups improved successively，the collagen fiber deposition and CaOx crystals decreased successively，and the CVF and CaOx crystal scores decreased. In the TGP+ML-099 group， renal tissue injury was further aggravated，collagen fiber deposition and CaOx crystals were further increased，and CVF and CaOx crystal scores were elevated. The BUN，Scr，24 h urine protein，IL-6，IL-1β，TGF-β1，α-SMA，p-Raf/Raf，p-MEK/MEK，and p-ERK/ERK in the KS group were higher than those in the Ctrl group（P<0.05）. The BUN，Scr，24 h urine protein，IL-6，IL-1β，TGF-β1，α-SMA，p-Raf/Raf，p-MEK/MEK and p-ERK/ERK in the L-TGP and H-TGP groups were lower than those in the KS group（P<0.05）. The BUN，Scr，24 h urine protein，IL-6，IL-1β，TGF-β1，α-SMA，p-Raf/Raf，p-MEK/MEK，and p-ERK/ERK in the TGP+ML-099 group were higher than those in the H-TGP group（P<0.05）. [Conclusion] TGP may suppress the inflammatory response，and improve renal fibrosis in KS rats by inhibiting the Raf/MEK/ERK pathway. |
| Key words: rapidly accelerated fibrosarcoma mitogen-activated extracellular signal-regulated kinase extracellular regulated protein kinase total glucosides of paeony kidney stones renal fibrosis |
