肥大细胞通过血管紧张素Ⅱ途径参与尿酸性肾损伤  

Mast Cells Participate in Uric Acid Nephropathy Through Angiotensin Ⅱ Pathway

作　　者：张明康 周燕[1] 武新安[1,3] ZHANG Ming-kang;ZHOU Yan;WU Xin-an(Department of Pharmacy,the First Hospital of Lanzhou University,Lanzhou 730000,Gansu,China;College of Pharmacy,Lanzhou University,Lanzhou 730020,Gansu,China;Engineering Research Centre of Prevention and Control Risk for Clinical Medicine of Gansu Province,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学第一医院药剂科,中国甘肃兰州730000 [2]兰州大学药学院,中国甘肃兰州730020 [3]甘肃省临床用药风险防控工程研究中心,中国甘肃兰州730000

出　　处：《生命科学研究》2022年第4期301-308,共8页Life Science Research

基　　金：国家自然科学基金资助项目(82060676,81960680);甘肃省青年科技基金(20JR5RA353);2020年甘肃省高等学校创新基金项目(2020B-010);2019年兰州市城关区科技计划项目(2019RCCX0039)。

摘　　要：基于肥大细胞介导的血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)途径初步探讨尿酸性肾损伤机制。将SD大鼠随机分为对照组和模型组,模型组按100 mg/(kg·d)的剂量灌胃腺嘌呤,喂食含10%酵母粉的饲料,经连续干预14 d、21 d和28 d构建尿酸性肾病大鼠模型。采用全自动生化分析仪检测血清尿素氮(blood urea nitrogen,BUN)、肌酐(serum creatinine,SCr)、胱抑素C(cystatin-C)水平以及血尿酸(serum uric acid,SUA)和尿尿酸(urinary uric acid,UUA)含量;借助HE、Masson和甲苯胺蓝染色观察大鼠肾脏病理学变化以及肥大细胞;通过UPLC-MS/MS技术检测大鼠肾脏尿毒素含量;采用试剂盒检测大鼠血清和肾脏谷胱甘肽(glutathione,GSH)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)的含量;利用ELISA方法检测大鼠血清AngⅡ含量。结果显示:随着造模天数增加,BUN、SCr、cystatin-C以及SUA的含量均显著性增加(P<0.05),UUA含量显著性下降(P<0.05);肾脏组织出现肾小管扩张、尿酸盐晶体沉积及纤维化损伤,与此同时,肥大细胞数量显著性增加(P<0.05);以硫酸吲哚酚和对甲酚硫酸盐为代表的尿毒素含量显著性增加(P<0.05);血清和肾脏中GSH、SOD和GSH-Px的含量显著性降低(P<0.05);血清AngⅡ含量显著性升高(P<0.05)。实验结果初步表明,随着造模天数增加,尿酸盐和尿毒素在肾脏蓄积量增加,大鼠肾脏损伤加重;肥大细胞参与尿酸性肾损伤,其通过促进AngⅡ的产生,促进氧化应激反应,使血清和肾脏GSH、SOD和GSH-Px含量降低,从而加重肾损伤。Based on the mast cell-mediated angiotensin Ⅱ(AngⅡ)pathway,the mechanism of renal injury in uric acid nephropathy was preliminarily explored.SD rats were randomly divided into control and model groups.The model groups were given adenine at a dose of 100 mg/(kg·d)and fed a diet containing 10%yeast powder.The rat model of uric acid nephropathy was established after continuous intervention for 14days,21 days and 28 days,respectively.The levels of blood urea nitrogen(BUN),serum creatinine(SCr),cystatin-C,serum uric acid(SUA)and urinary uric acid(UUA)were detected by an automatic biochemical analyzer.The pathological changes and mast cells in rat kidneys were observed by HE,Masson and toluidine blue staining.The urinary toxin content in rat kidney was detected by UPLC-MS/MS technology.The levels of serum and kidney glutathione(GSH),glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)were detected by testing kits.Meanwhile,the content of serum AngⅡ in rats was evaluated by ELISA.The results showed that,with the increase of modeling days,the contents of BUN,SCr,cystatin-C and SUA increased significantly(P<0.05),and the content of UUA decreased significantly(P<0.05).Renal histopathology revealed a significant increase in renal tubular dilatation,urate crystal deposition,fibrotic lesions,and a significant increase in the number of mast cells(P<0.05).The contents of urinary toxins represented by indoxyl sulfate and p-cresol sulfate were significantly increased(P<0.05).The contents of GSH,SOD and GSH-Px in sera and kidneys were significantly decreased(P<0.05).Serum AngⅡ content was significantly increased(P<0.05).The experimental results preliminarily showed that,with the increase of modeling days,the accumulation of urate and urine toxins in the kidneys increased,and the kidney damage in rats was aggravated.Mast cells were involved in uric acid kidney injury by promoting the production of AngⅡ and oxidative stress,and reducing serum and kidney GSH,SOD and GSH-Px levels.

关 键 词：尿酸性肾损伤 尿毒素 肥大细胞 血管紧张素Ⅱ(AngⅡ) 氧化应激 

分 类 号：Q256[生物学—细胞生物学] R692[医药卫生—泌尿科学]