黄芩-连翘不同配伍比例对痛风性肾病小鼠肾损伤的改善作用研究

Study on the Ameliorative Effect of Different Compatibility Ratios of Scutellaria baicalensis and Forsythia suspensa on Renal Injury in Mice with Gouty Nephropathy

关键词:  黄芩-连翘  配伍比例  痛风性肾病  肾损伤

Key words:  Scutellaria baicalensis-Forsythia suspensa  compatibility ratio  gouty nephropathy  renal injury

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及对其肾组织NLRP3/IL-1β/TGF-β1通路的影响。方法? 将小鼠随机分为6组:空白组、模型组、阳性药组(别嘌醇)、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,其余各组均通过灌胃给予腺嘌呤(100 mg/kg)和氧嗪酸钾(200 mg/kg)混合悬液,连续3周构建痛风性肾病模型。从造模第8 d起,对各组进行相应药物干预,持续给药14d。采用生化分析法评估小鼠肾功能,检测血清及肝脏中XOD、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重增长速度加快,24 h尿蛋白、血UA、BUN、Scr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GN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:

ABSTRACT: OBJECTIVE To investigate the therapeutic effects of Scutellaria baicalensis and Forsythia suspensa at different compatibility ratios on a mouse model of gouty nephropathy (GN) and their impact on the renal tissue NLRP3/IL-1β/TGF-β1 pathway. METHODS Mice were randomly divided into six groups: blank control group, model group, positive drug (allopurinol) group, Scutellaria-Forsythia (1:1) group, Scutellaria-Forsythia (2:3) group, and Scutellaria-Forsythia (1:2) group. Except for the control group, GN was induced in all other groups by intragastric administration of a mixture of adenine (100 mg/kg) and potassium oxonate (200 mg/kg) for 3 weeks. From the 8th day of modeling, corresponding drug interventions were administered to each group for 14 consecutive days. Biochemical analysis was used to assess renal function and measure the activity of Xanthine Oxidase (XOD) and Adenosine Deaminase (ADA) in serum and liver. HE staining and Masson staining were employed to observe renal histopathological changes. TUNEL staining was used to detect renal tissue cell apoptosis. Immunofluorescence and immunohistochemistry were applied to detect the protein expression of NLRP3, IL-1β, and TGF-β1. The 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, the groups treated with different compatibility ratios of Scutellaria baicalensis and Forsythia suspensa showed increased body weight gain, decreased 24-hour urinary protein, serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), and kidney index, along with increased urinary UA excretion. Morphological and structural damage to the kidneys was alleviated to varying degrees, the area of collagen fiber deposition in renal tissue was reduced, and the rate of renal cell apoptosis decreased. The protein expression of NLRP3, IL-1β, and TGF-β1 in renal tissue was downregulated, and the levels of TNF-α, IL-6, IL-18, IL-1β, and TGF-β1 were reduced. The most pronounced effects were observed in the Scutellaria-Forsythia (1:2) group. CONCLUSION The Scutellaria baicalensis and Forsythia suspensa combination at a 1:2 ratio exhibited the strongest renal protective effect in GN mice. The underlying mechanism is likely associated with the amelioration of renal injury through the suppression of the NLRP3/IL-1β/TGF-β1 signaling pathway.