木姜叶柯叶改善小鼠高尿酸血症肾病作用及其机制

Effects and Mechanism of Lithocarpus litseifoliu on Improving Hyperuricemia Nephropathy in Mice

目的探究木姜叶柯叶对小鼠高尿酸血症肾病(HN)肾功能和炎症的改善作用及潜在治疗机制。方法采用腺嘌呤和氧嗪酸钾联合给药建立HN模型,将小鼠随机分成正常对照组,模型对照组,苯溴马隆组,木姜叶柯叶大、中、小剂量组,分别给予不同药物,每周记录1次小鼠体质量,第21天采集并检测各组血清或尿液中尿酸(UA)、肌酐(Cr)、尿蛋白(UP)和血液尿素氮(BUN)、尿液尿素氮(UUN)及肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量;苏木精-伊红(HE)染色观察小鼠肾组织损伤情况;实时荧光定量聚合酶链反应(RT-PCR)测定肾组织中ABC转运蛋白G家族成员2(ABCG2)、尿酸转运蛋白1(URAT1)、葡萄糖转运体9(GLUT9)、核转录因子NF-κB p50(κB p50)。结果与正常对照组相比,模型对照组小鼠体质量在给造模药第2周后明显降低(P<0.05),UA、Cr、UP、BUN、UUN、TNF-α、IL-6含量及肾组织GLUT9、κB p50 mRNA表达含量显著升高(P<0.01或P<0.05)。与模型对照组相比,木姜叶柯叶大、中、小剂量组Cr、UP、BUN和UUN含量以及肾组织κB p50 mRNA表达显著降低(P<0.01或P<0.05),木姜叶柯叶大剂量组UA水平明显降低(P<0.05),中剂量组肾脏ABCG2 mRNA表达显著升高(P<0.01),小剂量组URAT1 mRNA表达显著降低(P<0.01)。结论木姜叶柯叶对小鼠高尿酸血症肾病有一定改善作用,其机制可能与调控肾脏尿酸转运蛋白、改善肾功能和抗炎有关。

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factorα(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P<0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA andκB p50 mRNA expression contents of kidney tissues were significantly higher(P<0.01,P<0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokineκB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P<0.01,P<0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P<0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P<0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P<0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.