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    黄芩-连翘不同配比对痛风性肾病小鼠肾损伤的改善作用

    Ameliorative Effect of Different Compatibility Ratios of Scutellariae Radix and Forsythiae Fructus on Renal Injury in Mice with Gouty Nephropathy

      摘要
    • 摘要:
      目的 探讨不同配伍比例黄芩-连翘对痛风性肾病模型小鼠的治疗作用，并基于NLRP3/IL-1β/TGF-β1通路探讨其具体机制。
      方法 将小鼠随机分为6组：空白组、模型组、阳性药(别嘌醇)组、黄芩-连翘1∶1组、黄芩-连翘2∶3组和黄芩-连翘1∶2组。除空白组外，其余各组均灌胃腺嘌呤(100 mg·kg−1)和氧嗪酸钾(200 mg·kg−1)混合悬液，连续3周构建痛风性肾病模型。从造模第8天起，对各组进行相应药物干预，持续给药14 d。采用生化分析法评估小鼠肾功能，检测血清及肝脏中黄嘌呤氧化酶(xanthine oxidase，XOD)、腺苷脱氨酶(adenosine deaminase，ADA)活性；HE染色及Masson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；采用免疫荧光及免疫组化检测NLRP3、IL-1β、TGF-β1的蛋白表达，通过ELISA法检测肾组织中TNF-α、IL-1β、IL-6、IL-18、TGF-β1水平。
      结果 与模型组比，黄芩-连翘不同配伍比例组小鼠体质量增长速度加快，24 h尿蛋白、血尿酸(uric acid，UA)、尿素氮、血肌酐及肾脏指数均降低，尿液中UA排泄增多，肾脏形态结构损伤有不同程度减轻，肾组织胶原纤维沉积面积缩小，肾组织细胞凋亡率降低，肾组织中NLRP3、IL-1β及TGF-β1蛋白表达均降低，肾组织中TNF-α、IL-6、IL-18、IL-1β及TGF-β1水平均降低，以黄芩-连翘1∶2时效果最佳。
      结论 黄芩-连翘配伍比例为1∶2时对痛风性肾病小鼠的肾保护作用最强，其机制可能是通过抑制NLRP3/IL-1β/TGF-β1信号通路改善肾损伤而实现。

       

      Abstract:
      OBJECTIVE To evaluate the therapeutic effects of Scutellariae Radix and Forsythiae Fructus at different compatibility ratios in a mouse model of gouty nephropathy, with a focus on the mechanisms involving the NLRP3/IL-1β/TGF-β1 signaling pathway.
      METHODS Mice were randomly assigned to six groups: blank control, model group, positive control(allopurinol) group, and three Scutellariae Radix-Forsythiae Fructus groups with compatibility ratios of 1∶1, 2∶3, and 1∶2. Gouty nephropathy was induced in all groups except the blank group by oral administration of adenine(100 mg·kg−1) and potassium oxonate(200 mg·kg−1) suspension for 3 weeks. From 8th day of modeling, each treatment group received the corresponding drug intervention for 14 consecutive days. Renal function parameters, along with serum and hepatic xanthine oxidase(XOD) and adenosine deaminase(ADA) activities, were assessed biochemically. Renal histopathology was examined via HE and Masson staining, while apoptosis was detected by TUNEL assay. The protein expression of NLRP3, IL-1β, and TGF-β1 was evaluated using immunofluorescence and immunohistochemistry. Levels of TNF-α, IL-1β, IL-6, IL-18, and TGF-β1 in renal tissue were measured by ELISA.
      RESULTS Compared with the model group, all Scutellariae Radix-Forsythiae Fructus treatment groups exhibited increased body weight gain, reduced 24-hour urinary protein, serum uric acid(UA), blood urea nitrogen(BUN), serum creatinine(Scr), and kidney index, along with elevated urinary UA excretion. Renal histopathological injury, collagen deposition, and apoptosis were also alleviated. Furthermore, protein expression of NLRP3, IL-1β, and TGF-β1 was downregulated, and levels of renal TNF-α, IL-6, IL-18, IL-1β, and TGF-β1 were reduced. The most significant improvements were observed in the 1∶2 Scutellariae Radix-Forsythiae Fructus group.
      CONCLUSION The 1∶2 combination of Scutellariae Radix and Forsythiae Fructus provide the most pronounced renoprotective effect in GN mice, likely mediated through suppression of the NLRP3/IL-1β/TGF-β1 signaling pathway.

       

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