石淋清颗粒对大鼠草酸钙肾结石的影响及机制  

Effect of Shilinqing granules on calcium oxalate nephrolithiasis in rats and its mechanism

作　　者：杨雄 靳潇潇 李卫胜 郑聪 何文强 YANG Xiong;JIN Xiaoxiao;LI Weisheng;ZHENG Cong;HE Wenqiang(Dept.of Urology and Andrology,Nanyang Second General Hospital,Henan Nanyang 473000,China;Section Two,Dept.of Urology,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450003,China)

机构地区：[1]南阳市第二人民医院泌尿男科,河南南阳473000 [2]河南中医药大学第一附属医院泌尿外科二区,郑州450003

出　　处：《中国药房》2024年第22期2750-2755,共6页China Pharmacy

基　　金：河南省卫生健康委国家中医药传承创新科研专项(No.2023ZXZX1089);河南省中医药科学研究专项课题(No.2024ZY2045)。

摘　　要：目的基于沉默信息调节因子1(SIRT1)/核因子κB(NF-κB)/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)信号通路探讨石淋清颗粒对大鼠草酸钙肾结石的影响及潜在机制。方法将60只雄性SD大鼠随机分为对照组,模型组,石淋清颗粒低、中、高剂量组(6.5、13、26 g/kg,以生药量计)和石淋清颗粒高剂量+抑制剂组(石淋清颗粒26 g/kg+SIRT1抑制剂尼克酰胺5 mg/kg),每组10只。除对照组外,其余各组大鼠均自由饮用1%乙二醇溶液并灌胃2%氯化铵溶液2 mL(每天1次,连续4周),以构建草酸钙肾结石模型。造模同时,各药物组大鼠灌胃或(和)腹腔注射相应药液,对照组和模型组灌胃生理盐水并腹腔注射二甲基亚砜。检测各组大鼠体重、肾脏指数、尿液/血清生化指标[24 h尿量、尿pH、尿钙离子(Ca^(2+))和尿草酸(Ox)含量,以及血肌酐(Scr)、血尿素氮(BUN)、血Ca^(2+)含量]、血清炎症指标[白细胞介素1β(IL-1β)、IL-18水平],观察其肾组织病理变化、草酸钙结晶情况并进行结晶评分,检测其肾组织中SIRT1、NLRP3、NF-κB蛋白的表达情况。结果与对照组相比,模型组大鼠肾组织损伤严重并可见大量草酸钙结晶;其体重、24 h尿量、尿pH及肾组织中SIRT1蛋白的表达均显著降低或下调(P<0.05);结晶评分,肾脏指数,尿Ca^(2+)、Ox含量,血清中Scr、BUN、Ca^(2+)含量和IL-1β、IL-18水平,以及肾组织中NF-κB、NLRP3蛋白的表达均显著升高或上调(P<0.05)。与模型组相比,石淋清颗粒各剂量组大鼠肾组织病理改变有所好转,草酸钙结晶有所减少,各定量指标均显著改善(P<0.05);而SIRT1抑制剂可显著逆转高剂量石淋清颗粒对上述指标的改善作用(P<0.05)。结论石淋清颗粒可抑制大鼠草酸钙肾结石的形成,降低炎症指标水平;其机制可能与上调SIRT1蛋白表达,下调NF-κB、NLRP3蛋白表达有关。OBJECTIVE To explore the effect of Shilinqing granules on calcium oxalate nephrolithiasis in rats and its potential mechanisms through the silence information regulator 1(SIRT1)/nuclear factor-κB(NF-κB)/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)signaling pathway.METHODS Sixty male SD rats were randomly assigned to control group,model group,and low-,medium-,high-dose groups of Shilinqing granules(6.5,13,26 g/kg,calculated based on crude drug),and high-dose of Shilinqing granules+inhibitor group(Shilinqing granules 26 g/kg+SIRT1 inhibitor nicotinamide 5 mg/kg),with 10 rats in each group.Except for the control group,the remaining groups of rats were given 1%ethylene glycol solution to drink freely and were intubated with 2%ammonium chloride solution 2 mL(once a day,for 4 weeks)to construct a calcium oxalate nephrolithiasis model.At the same time of modeling,the administration groups were intubated or(and)intraperitoneally injected with the corresponding drug solutions,while the control and the model groups were intubated with physiological saline and intraperitoneally injected with dimethyl sulfoxide.The body weight,kidney index,urine/blood biochemical indicators[24-hour urine volume,urine pH,urinary calcium ion(Ca^(2+))and urinary oxalic acid(Ox)content,as well as blood creatinine(Scr),blood urea nitrogen(BUN),blood Ca^(2+)content],serum inflammatory indicators[levels of interleukin-1β(IL-1β),IL-18],pathological changes in renal tissue,calcium oxalate crystallization,and crystal scoring were observed.The protein expressions of SIRT1,NLRP3,and NF-κB in renal tissue were detected.RESULTS Compared with the control group,the model group had severe renal tissue damage and a large number of calcium oxalate crystals,with significant decrease or downregulation in body weight,24-hour urine volume,urine pH,and protein expression of SIRT1 in renal tissue(P<0.05);crystal score,kidney index,urinary contents of Ca^(2+)and Ox,serum contents of Scr,BUN and Ca^(2+),and serum lev

关 键 词：石淋清颗粒 草酸钙肾结石 炎症反应 SIRT1/NF-κB/NLRP3信号通路 

分 类 号：R965[医药卫生—药理学]