基于IL-1β探讨矢志方对高尿酸血症小鼠肾组织OAT1/3表达的影响  

Effects of Shizhi Prescription on the Expression of OAT1/3 in the Renal Tissue of Hyperuricemic Mice Based on IL-1β

作　　者：王传旭 周嘉宝 吴志远 吴燕升 郭亚芳 高建东[1] WANG Chuanxu;ZHOU Jiabao;WU Zhiyuan;WU Yansheng;GUO Yafang;GAO Jiandong(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Nephropathy Institute of Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Ministry of Education,Key Laboratory of Liver and Kidney Diseases,Shanghai University of Traditional Chinese Medicine,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai 201203,China;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Fudan University Pudong Medical Center,Shanghai 201399,China)

机构地区：[1]上海中医药大学附属曙光医院,上海中医药大学中医肾病研究所,上海中医药大学肝肾疾病病证教育部重点实验室,上海市中医临床重点实验室,上海201203 [2]上海中医药大学附属龙华医院,上海200032 [3]复旦大学附属浦东医院,上海201399

出　　处：《中国中医药信息杂志》2022年第12期70-75,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81874437、81904126);上海市科委项目(20Y21901800);上海市浦东新区卫生系统重点学科群建设项目(PWZxq2017-07);上海市进一步加快中医药事业发展三年行动计划[ZY(2018-2020)-CCCX-2003-08、ZY(2018-2020)-FWTX-7005]。

摘　　要：目的基于炎症因子白细胞介素(IL)-1β观察矢志方对高尿酸血症(HUA)小鼠肾组织有机阴离子转运蛋白1/3(OAT1/3)表达的影响,探讨其作用机制。方法32只SPF级雄性BALB/c小鼠随机分为正常组、模型组、非布司他组和矢志方组,每组8只。正常组予生理盐水灌胃,其余各组予氧嗪酸钾250 mg/kg灌胃制备HUA小鼠模型。非布司他组和矢志方组造模同时分别按6 mg/kg、562.5 mg/kg灌胃相应药物,正常组和模型组予生理盐水灌胃,连续2周。HE和Masson染色观察肾组织病理变化,Western blot和免疫荧光染色检测肾组织IL-1β、OAT1、OAT3及肝细胞核因子(HNF)1α、HNF4α表达。结果与正常组比较,模型组小鼠肾小管管壁变薄,管腔扩张,炎性细胞浸润,肾间质纤维组织增生,肾组织IL-1β蛋白表达显著升高(P<0.001),OAT1、OAT3、HNF1α、HNF4α蛋白表达显著降低(P<0.01,P<0.001);与模型组比较,矢志方组小鼠肾小管管壁变薄、管腔扩张、纤维组织增生有所减轻,炎性细胞浸润减少,肾组织IL-1β蛋白表达显著降低(P<0.05),OAT1、OAT3、HNF1α、HNF4α蛋白表达显著升高(P<0.05,P<0.01)。免疫荧光染色结果与Western blot结果一致。结论矢志方减轻肾脏病理损伤的机制可能与抑制HUA小鼠肾组织炎症因子IL-1β表达,促进OAT1/3、HNF1α/4α表达有关。Objective To observe the effects of Shizhi Prescription on the expression of organic anion transporter 1/3(OAT1/3)in renal tissue of hyperuricemia(HUA)mouse based on IL-1β;To discuss its mechanism of action.Methods Totally 32 SPF male BALB/c mice were randomly divided into normal group,model group,febuxostat group,and Shizhi Prescription group,with 8 mice in each group.The normal group was given normal saline by gavage,the other groups were given 250 mg/kg potassium oxazine by gavage to prepare the HUA mouse model.The febuxostat group and the Shizhi Prescription group were treated with corresponding drugs by intragastric administration of 6 mg/kg and 562.5 mg/kg,respectively,while the normal group and the model group were given normal saline by gavage for 2 consecutive weeks.The pathological changes in renal tissue were observed by HE and Masson staining,Western blot and immunofluorescence staining were used to detect the expression of IL-1β,OAT1,OAT3,HNF1α,HNF4αin renal tissue.Results Compared with the normal group,the renal tubular wall of mice in the model group became thinner,the lumen was dilated,the inflammatory cells infiltrated,and the renal interstitial fibrous tissue proliferated,the expression of IL-1βprotein in renal tissue significantly increased(P<0.001),and the expressions of OAT1,OAT3,HNF1α,HNF4αprotein significantly decreased(P<0.01,P<0.001).Compared with the model group,the pathological changes of renal tubular wall became thinner,the lumen was dilated,fibrotic tissue hyperplasia was alleviated,inflammatory cell infiltration was reduced,and the expression of IL-1βprotein in renal tissue was significantly decreased(P<0.05),and the expressions of OAT1,OAT3,HNF1α,HNF4αprotein significantly increased(P<0.05,P<0.01).The results of immunofluorescence staining were consistent with those of Western blot.Conclusion The mechanism of Shizhi Prescription in alleviating the pathological damage to the kidney may be related to promoting the expression of OAT1/3 and HNF1α/4αin renal tissue of HUA mi

关 键 词：矢志方 高尿酸血症 有机阴离子转运蛋白1/3 白细胞介素-1Β 肝细胞核因子1α/4α 小鼠 

分 类 号：R285.5[医药卫生—中药学]