【摘要】 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 monophosphate response 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。更多还原

【Abstract】 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 RUNX2expressions 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.更多还原