目的 基于核因子-κB（nuclear factor-κB，NF-κB）/环磷酸腺苷应答元件结合蛋白（cyclic adenosine monophosphateresponse element blinding protein，CREB）/核心结合蛋白因子2（runt-related transcription factor-2，RUNX2）通路探讨蒲公英水提物对肾结石大鼠肾脏的保护作用。方法 通过向饮用水中加入2%氯化铵、1%乙二醇制备肾结石大鼠，将造模大鼠随机分为模型组、蒲公英水提物（低、高剂量100、200 mg/kg）组、排石颗粒（100 mg/kg）组和蒲公英水提物（200 mg/kg）＋NF-κB激活剂（佛波酯，5 mg/kg）组，并以正常大鼠为对照组。给予药物干预后，检测大鼠肾功能指标[尿素氮（urea nitrogen，BUN）、血肌酐（blood creatinine，Scr）]、尿生化指标（尿蛋白、Ca²⁺）、肾脏指数、血清中炎性因子[白细胞介素-6（interleukin-6，IL-6、IL-1β]、肾组织中氧化应激指标[丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）]水平；采用苏木素-伊红（HE）染色观察肾组织病理变化； TUNEL染色检测肾组织细胞凋亡情况； Western blotting检测肾组织中NF-κB/CREB/RUNX2通路相关蛋白表达。结果 与对照组比较，模型组大鼠血清中BUN、Scr、尿蛋白、Ca²⁺、IL-6、IL-1β水平以及肾脏指数、肾组织MDA水平、细胞凋亡率、肾组织p-NF-κB p65/NF-κB p65、p-CREB/CREB、RUNX2表达均显著升高（P＜0.05），肾组织SOD活性显著降低（P＜0.05）。与模型组比较，蒲公英水提物各剂量组和排石颗粒组血清中BUN、Scr、尿蛋白、Ca²⁺、IL-6、IL-1β水平以及肾指数、肾组织MDA水平、细胞凋亡率、p-NF-κB p65/NF-κB p65、p-CREB/CREB、RUNX2表达显著降低（P＜0.05），肾组织SOD活性显著升高（P＜0.05）。给予NF-κB激活剂后，蒲公英水提物对以上指标的作用均被显著逆转（P＜0.05）。结论 蒲公英水提物可通过调节NF-κB/CREB/RUNX2通路保护肾结石大鼠肾脏。

Objective To explore the protective effect of water extract of Pugongying (Taraxaci Herba) on kidney of rats with kidney stones based on nuclear factor-κB (NF-κB)/cyclic adenosine monophosphate response element blinding protein (CREB)/runt-related transcription factor-2 (RUNX2) pathway. Methods Kidney stone rats were prepared by adding 2% ammonium chloride and 1% ethylene glycol to drinking water. The model rats were randomly divided into model group, water extract of Taraxaci Herba low-, high-dose (100, 200 mg/kg) groups, Paishi Granules (排石颗粒, 100 mg/kg) group and water extract of Taraxaci Herba (200 mg/kg) + NF-κB-activator (phorbol ester, 5 mg/kg) group, with normal rats as the control group. After drug intervention, renal function indicators such as urea nitrogen (BUN), serum creatinine (Scr), urine biochemistry indicators such as urinary protein and Ca²⁺, renal index, inflammatory factors such as interleukin-6 (IL-6) and IL-1β in serum and oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) in renal tissue were detected; Hematoxylin-eosin (HE) staining was used to observe pathological changes in renal tissue; TUNEL staining was used to detect apoptosis in renal tissue cells; Western blotting was used to detect the expressions of NF-κB/CREB/RUNX2 pathway related proteins in renal tissue. Results Compared with control group, levels of BUN, Scr, urinary protein, Ca²⁺, IL-6, IL-1β in serum and renal index, MDA level, cell apoptosis rate, p-NF-κB p65/NF-κB p65, p-CREB/CREB and RUNX2 expressions in renal tissue of rats in model group were significantly increased (P < 0.05), SOD activity in renal tissue was significantly decreased (P < 0.05). Compared with model group, levels of BUN, Scr, urinary protein, Ca²⁺, IL-6, IL-1β in serum and renal index, MDA level, cell apoptosis rate, p-NF-κB p65/NF-κB p65, p-CREB/CREB and RUNX2 expressions in renal tissue of rats in water extract of Taraxaci Herba low-, high-dose groups and Paishi Granules group were significantly reduced (P < 0.05), SOD activity in renal tissue was significantly increased (P < 0.05). After administering NF-κB activators, the effects of water extract of Taraxaci Herba on the above indicators were significantly reversed (P < 0.05). Conclusion Water extract of Taraxaci Herba can protect the kidney of rats with kidney stones by regulating NF-κB/CREB/RUNX2 pathway.

R285.5

黑龙江省省属高等学校基本科研业务费科研项目（2020-KYYWFMY-0030）