清利湿热方调节IL27/IL12RB1/CCR7信号通路改善高尿酸血症大鼠肾脏炎性状态作用机制  

Mechanism of Qingli Shire Formula in improving renal infammatory state in hyperuricemic rats by regulating IL27/IL12RB1/CCR7 signal pathway

作　　者：邸松蕊 刘金莲 张建军 姜砚馨 张惠 南海鹏 朱映黎[2] 王淳 王林元[2] DI Songrui;LIU Jinlian;ZHANG Jianjun;JIANG Yanxin;ZHANG Hui;NAN Haipeng;ZHU Yingli;WANG Chun;WANG Linyuan(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;Schoolof Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中医学院,北京102488 [2]北京中医药大学中药学院,北京102488

出　　处：《中华中医药杂志》2025年第2期605-612,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重点研发计划“中医药现代化研究重点专项”(No.2018YFC1706800)。

摘　　要：目的:探讨清利湿热方通过调控IL27/IL12RB1/CCR7信号通路改善高尿酸血症大鼠肾脏炎性状态的作用及机制。方法:实验一:将56只雄性SD大鼠随机分为空白组、模型1组、阳性对照1组、模型2组、阳性对照2组、模型3组、阳性对照3组,模型1、2、3组连续30 d分别灌胃750、1 000、1 500 mg/kg氧嗪酸钾,以等剂量27 mg/kg别嘌呤醇为阳性对照,通过血尿酸(SUA)水平验证各组模型高尿酸血症是否成立,并观察不同造模剂量氧嗪酸钾对大鼠体质量、血尿素氮(BUN)、血肌酐(Scr)、肾脏组织病理的影响,综合评价各模型肾脏改变的程度。实验二:将48只雄性SD大鼠随机分为空白组,模型组(1 000 mg/kg氧嗪酸钾),阳性对照组(27 mg/kg别嘌呤醇),清利湿热方低、中、高剂量组(1.25、2.5、5g/kg),观察清利湿热方对高尿酸血症肾脏轻度炎性状态模型大鼠体质量、SUA、BUN、Scr、肾脏组织病理的影响,利用RT-qPCR和Western Blot分别测定肾脏白介素27(IL27)、白介素12受体B1亚型(IL12RB1)及趋化因子受体7(CCR7)mRNA及蛋白表达。结果:实验一:与空白组比较,模型1、2、3组SUA含量显著升高(P<0.05),模型3组Scr含量显著升高(P<0.05);模型1组肾脏组织未见明显变化,模型2组可见少量肾小管轻度颗粒变性,胞质内可见嗜酸性颗粒,模型3组肾皮质局部可见周围间质中伴有结缔组织增生及淋巴细胞浸润。与各模型组比较,相应的阳性对照组SUA含量均显著降低(P<0.05)。实验二:与空白组比较,模型组SUA含量显著升高(P<0.05),肾脏可见少量淋巴细胞浸润,IL27、IL12RB1 mRNA及蛋白表达均显著升高(P<0.05),CCR7 mRNA表达显著升高(P<0.05),蛋白表达显著降低(P<0.05)。与模型组比较,各给药组SUA含量均显著降低(P<0.05);阳性对照组肾皮质中可见少量肾小囊腔内有嗜酸性物质渗出,清利湿热方各剂量组肾脏组织未见明显的病理变化;清利湿热方高剂量组IL27、IL12RB1 mRNA与蛋�Objective:To discuss the effect and mechanism of Qingli Shire Formula in improving the renal infammatory state of hyperuricemia rats by regulating the IL27/IL12RB1/CCR7 signal pathway.Methods:Experiment 1:a total of 56 male SD rats were randomly divided into blank group,model 1 group,positive control 1 group,model 2 group,positive control 2 group,model 3 group,and positive control 3 groups.Model 1,2,and 3 groups were given 750 mg/kg,1000 mg/kg,and 1500 mg/kg potassium oxazinate by gavage for 30 consecutive days,the same dose of 27 mg/kg allopurinol was used as the positive control to verify whether the hyperuricemia model in each group was established by the level of blood uric acid(SUA),and the effects of different modeling doses of potassium oxazinate on the weight,blood urea nitrogen(BUN),blood creatinine(Scr),and renal histopathology of rats were observed,and the degree of renal changes in each model was comprehensively evaluated.Experiment 2:a total of 48 male SD rats were randomly divided into blank group,model group(1000 mg/kg potassium oxazinate),positive control group(27 mg/kg allopurinol),low,medium,and high dose group of Qingli Shire Formula(1.25,2.5,and 5 g/kg).To observe the effect of Qingli Shire Formula on body weight,SUA,BUN,Scr,and renal histopathology of rats with mild renal inflammation in hyperuricemia.The mRNA and protein expressions of interleukin-27(IL27),interleukin-12 receptor B1 subtype(IL12RBI),and Chemokine receptor 7(CCR7)in the kidney were measured by RT-qPCR and Western blot.Results:Experiment 1:Compared with the blank group,the SUA content in model 1,model 2,and model 3 groups significantly increased(P<0.05),the Scr content in model 3 groups increased(P<0.05).There was no significant change in the renal tissue of model 1 group.In model 2 group,a small amount of mild granular degeneration of renal tubules was observed,with eosinophilic particles visible in the cytoplasm.In model 3 group,there was local connective tissue proliferation and lymphocyte infiltration in the surrounding in

关 键 词：高尿酸血症 清利热湿 清利湿热方 肾脏炎性 氧嗪酸钾 IL27/IL12RB1/CCR7信号通路 

分 类 号：R73[医药卫生—肿瘤]