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DOI:
:2018,32(3):80-85
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降尿酸复方对高尿酸血症大鼠氧化应激及肾脏炎症状态的影响
王毅兴1,吴燕升2,张春燕1,高建东2
(1.同济大学附属东方医院中医科(上海200120);2.上海中医药大学附属曙光医院肾病科,上海中医药大学中医肾病研究所,肝肾疾病病证教育部重点实验室(上海中医药大学) ,上海市中医临床重点实验室(上海201203))
Effects of compound recipe of reducing uric acid on oxidative stress and renal inflammatory state in rats with hyperuricemia
WANG Yixing1,WU Yansheng2,ZHANG Chunyan1,GAO Jiandong2
(1.Department of Chinese Medicine,East Hospital Affiliated to Tongji University,Shanghai 200120,China;2.Department of Nephropathy,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Nephropathy Institute of Chinese Medicine,Shanghai University of Traditional Chinese Medicine; Key Laboratory of Ministry of Education for Liver and Kidney Diseases,Shanghai University of Traditional Chinese Medicine; Shanghai Key Laboratory of Clinical Chinese Medicine,Shanghai 201203,China)
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中文摘要:   目的:评价降尿酸复方对高尿酸血症大鼠尿酸及氧化应激的作用,并检测对肾脏炎症状态影响。  方法:将28只SD大鼠随机分为正常组、模型组、西药组和中药组,每组7只;除正常组外,其他各组以氧嗪酸钾灌胃造模,同时正常组、模型组灌胃蒸馏水,西药组与中药组以成人10倍剂量分别灌胃别嘌呤醇、降尿酸复方,连续7周。实验结束取样,检测大鼠血尿酸(UA)、尿尿酸(UUA)及肾功能;检测血清及肾组织NO、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)活性及脂质过氧化物MDA水平;以免疫荧光法检测各组大鼠肾组织Nod样受体蛋白3(NLRP3)和IL-1β表达。  结果:与模型组比较,两药物组的UA水平均显著降低(P<0.05),且中药组与西药组比较无显著性差异(P>0.05);中药组的随机UUA浓度显著升高(P<0.05),而西药组无明显改善(P>0.05)。两药物组血清NO、CAT、GSH-PX、SOD活力均显著提高(P<0.05),MDA显著降低(P<0.05),且在血清GSH-PX水平上中药组优于西药组(P<0.05);两药物组肾脏组织匀浆GSH-PX、SOD活力显著提高(P<0.05),MDA显著降低(P<0.05),而NO水平无明显改变(P>0.05),西药组CAT水平明显提高(P<0.05),但与中药组比较无统计学差异(P>0.05)。肾组织免疫荧光染色显示,中药组和西药组大鼠肾组织中NLRP3和IL-1β的表达均较模型组明显下调。  结论:降尿酸复方能够有效降低高尿酸血症大鼠血尿酸水平,减轻高尿酸血症大鼠体内和肾内氧化应激,调节NLRP3炎性体表达。
Abstract:  Objective:To evaluate the effects of compound recipe of reducing uric acid on uric acid and oxidative stress in rats with hyperuricemia,and examine the effects on renal inflammatory state.   Methods:28 SD rats were randomly divided into the normal group,model group,western medicine group and Chinese medicine group,7 rats in each group. Except the normal group,the other groups were treated with potassium oxonate by intragastric administration to establish the model. Meanwhile,the normal group and model group were treated with distilled water by intragastric administration,the western medicine group and Chinese medicine group were treated with allopurinol and compound recipe of reducing uric acid at dose as 10 times as adult’s dosage,respectively,with a course of 7 continuous weeks. At the end of the experiment,the samples were collected. The levels of blood uric acid(UA),urinary uric acid(UUA) and renal function indexes were detected,and the activities of nitric oxide(NO),superoxide dismutase(SOD),glutathione peroxide(GSH-PX) and catalase(CAT) and the level of lipid peroxides malondialdehyde(MDA) in serum and renal tissue were detected. The expressions of Nod-like receptor protein 3(NLRP3) and interleukin-1β(IL-1β) in the renal tissue of rats were detected by immunofluorescence assay.   Results:Compared with the model group,the UA level in the two drug treatment groups was significantly decreased(P<0.05),and there was no statistically significant difference on the UA level between the Chinese medicine group and western medicine group(P>0.05). The random UUA concentration in the Chinese medicine group was significantly increased(P<0.05),while no obvious change was observed in the western medicine group(P>0.05). The serum activities of NO,CAT,GSH-PX and SOD in the two drug treatment groups were significantly increased(P<0.05),and the serum MDA level was significantly decreased(P<0.05),and the serum GSH-PX level in the Chinese medicine group was higher than that in the western medicine group(P<0.05). The GSH-PX and SOD activities in renal homogenate in the two drug treatment groups were significantly increased(P<0.05),and the MDA level was significantly decreased(P<0.05),but no change on NO level was found(P>0.05). The CAT activity in the western medicine group was significantly increased(P<0.05),but there was no statistically significant difference on the CAT activity between the Chinese medicine group and western medicine group(P>0.05). The renal immunofluorescence staining showed that the expressions of NLRP3 and IL-1β in the renal tissue in the Chinese medicine group and western medicine group were significantly down-regulated compared with the model group.   Conclusion:Compound recipe of reducing uric acid can effectively reduce the level of blood uric acid in rats with hyperuricemia,alleviate the oxidative stress in blood and kidney of hyperuricemia rats,and regulate the expression of NLRP3 inflammasome.
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基金项目:国家自然科学基金资助项目(81373613);上海市浦东新区名中医继承人培养建设项目(PDZYXK-6-2014024);浦东新区名中医及名中医工作室建设项目(PDZYXK-3-2014014);上海市科委专荐经费资助项目(16140903500) [
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