降尿酸方对高尿酸血症肾病大鼠内皮功能的影响
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国家自然科学基金项目(81874437);上海市卫建委科研项目(202040120);上海市海派中医丁氏内科浦东基地建设项目(PDZY-2019-0701);浦东医院特色专病(诊治中心)建设项目(TSZB2020-06,YJRCJJ201806)


Effect of Jiangniaosuan Prescription on the Endothelial Function of Rats with Uric Acid Nephropathy
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    摘要:

    目的:探究降尿酸方对氧嗪酸钾联合腺嘌呤造模高尿酸血症肾病大鼠内皮型一氧化氮合酶(eNOS),内皮素(ET)的影响。方法:将40只8周龄无特定病原(SPF)级雄性SD大鼠随机分为正常组、模型组、别嘌醇组和降尿酸方组。正常组灌胃2 mL/d灭菌蒸馏水,2次/d,模型组采用上午氧嗪酸钾1 500 mg/(kg·d)联合腺嘌呤100 mg/(kg·d)灌胃,下午2 mL/d灭菌蒸馏水4周诱导高尿酸血症肾病模型。别嘌醇组,降尿酸方组,上午与模型组相同。下午别嘌醇组给予大鼠灌胃2.5 mg/100 g剂量别嘌醇灌胃,降尿酸方组给予大鼠灌胃1.6 g/(100 g·mL)剂量灌胃。治疗4周后处死,检测血肌酐(Scr)、血尿酸(SUA)、尿素氮(BUN)。观察肾功能,电镜观察肾脏内皮病变,实时聚合酶链式反应技术(Real-time PCR)检测eNOS mRNA,ET mRNA表达水平。免疫组织化学检测eNOS、ET的表达。结果:与正常组比较,模型组Scr、SUA、BUN显著升高(P<0.05),电镜显示肾脏内皮细胞损伤严重。肾组织eNOS mRNA的表达降低(P<0.05)。肾组织ET mRNA的表达升高(P<0.05)。免疫组织化学显示eNOS表达下降,ET-1表达升高。与模型组比较,别嘌醇组和降尿酸方组Scr、SUA、BUN降低(P<0.05),电镜显示大鼠肾脏内皮损伤改善,肾组织eNOS mRNA的表达升高(P<0.05)。肾组织ET mRNA的表达降低(P<0.05)。免疫组织化学显示eNOS表达升高,ET-1表达下降。结论:降尿酸方通过促进eNOS基因的表达,抑制ET基因的表达改善高尿酸血症肾病大鼠内皮功能,达到保护肾脏的目的。

    Abstract:

    To study the effects of Jiangniaosuan prescription on endothelial nitric oxide synthase(eNOS) and endothelin(ET) in rats with hypoxanthine and adenine-induced uric acid(UA) nephropathy.Methods:Forty 8-week-old male SD rats of SPF grade were randomly divided into a normal group,a model group,an allopurinol group,and a Jiangniaosuan prescription group,with 10 rats in each group.The normal group was given 2 ml/d acidified water by gavage twice a day.All groups were given hypoxanthine 1 500 mg/(kg·d) and adenine 100 mg/(kg·d) in the morning for 4 weeks except the normal group.The model group was given 2 mL/d acidified water by gavage in the afternoon for 4 weeks.The allopurinol group was given allopurinol(2.5 mg/100 g) by gavage in the afternoon.The Jiangniaosuan prescription group was given Jiangniaosuan prescription 1.6 g/(100 g·mL) by gavage in the afternoon.The rats were sacrificed after 4-week treatment,and the serum creatinine(Scr),blood urea nitrogen(BUN),and UA were detected.The renal function of rats was observed,and the renal endothelial lesion was measured by electron microscopy.Real-time quantitative polymerase chain reaction(real-time PCR) was used to determine the expression levels of messenger ribonucleic acid(mRNA) of eNOS and ET.The expressions of eNOS and ET were detected by immunocytochemistry.Results:Compared with the normal group,the Scr,serum uric acid(SUA),BUN,and UA of rats in the model group were significantly increased(P<0.05),and the cells of renal endothelium were severely damaged.The mRNA expression of eNOS in the kidney tissue was decreased(P<0.05),and the mRNA expression of ET in the kidney tissue was increased(P<0.05).The results of immunocytochemistry showed that eNOS expression decreased,whereas ET-1 expression increased.Compared with the model group,the Scr,BUN,and UA of rats in the allopurinol group and the Jiangniaosuan prescription group were decreased(P<0.05),and the renal endothelial function was improved.The mRNA expression of eNOS in the kidney tissue was increased(P<0.05),and the mRNA expression of ET in the kidney tissue was decreased(P<0.05).The results of immunocytochemistry showed that eNOS expression increased,whereas ET-1 expression decreased.Conclusion:Jiangniaosuan prescription improved the endothelial function of rats with UA nephropathy by promoting the expression of eNOS gene and inhibiting the expression of ET gene,thus protecting the kidney.

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郭亚芳,丁铃,乔春萍,周嘉宝,李东东,甘静,张长明,高建东.降尿酸方对高尿酸血症肾病大鼠内皮功能的影响[J].世界中医药,2022,(07).

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  • 收稿日期:2020-05-12
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  • 在线发布日期: 2022-05-26
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