文章摘要
王庆婷,崔 颖,李云飞,黄智敏,袁杨刚,钱 军,叶扬帆,Yogendranath Purrunsing,王宁宁.调整腺嘌呤饮食磷含量制作慢性肾病高磷血症的小鼠模型[J].南京医科大学学报,2018,(7):956~961
调整腺嘌呤饮食磷含量制作慢性肾病高磷血症的小鼠模型
Adjusting phosphorus content in adenine diet to establish mice model of chronic kidney disease with hyperphosphatemia
投稿时间:2018-03-31  
DOI:10.7655/NYDXBNS20180716
中文关键词: 高磷血症  腺嘌呤  小鼠模型  纤维化  炎症
英文关键词: hyperphosphatemia  adenine  mice model  fibrosis  inflammatory
基金项目:国家自然科学基金 (81270408,81570666);国际肾脏病学会临床研究项目 (18?01?0247);江苏省临床医学研究中心支撑体系建设(BL2014084);江苏省“医学重点人才”项目 (ZDRCA2016002,RC201162);江苏省研究生创新工程(KYLX161094)
作者单位
王庆婷 南京医科大学第一附属医院肾内科江苏 南京 210029 
崔 颖 南京医科大学第一附属医院肾内科江苏 南京 210029 
李云飞 南京医科大学第一附属医院检验学部江苏 南京 210029 
黄智敏 南京医科大学第一附属医院肾内科江苏 南京 210029 
袁杨刚 南京医科大学第一附属医院肾内科江苏 南京 210029 
钱 军 南京医科大学第一附属医院肾内科江苏 南京 210029 
叶扬帆 南京医科大学第一临床医学院江苏 南京 211166 
Yogendranath Purrunsing 南京医科大学第一附属医院肾内科江苏 南京 210029 
王宁宁 南京医科大学第一附属医院肾内科江苏 南京 210029 
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中文摘要:
      目的:通过调整腺嘌呤饮食中的磷水平,建立慢性肾脏病伴高磷血症的小鼠模型。方法:将雄性C57BL/6小鼠分为腺嘌呤饮食组(腺嘌呤0.2%,钙1.0%,磷0.6%)及其对照组(钙1.0%,磷0.6%)、腺嘌呤联合高磷饮食组(腺嘌呤0.2%,钙0.6%,磷1.0%)及其对照组(钙0.8%,磷0.6%),每组各7只。于造模前、造模4周记录体重,测血尿素氮(BUN)、钙(Ca)、磷(P)水平,4周后取肾脏组织,RT?PCR检测肾纤维化指标包括Ⅰ型胶原蛋白(CollagenⅠ)、纤连蛋白(fibronectin,FN)、纤溶酶原激活物抑制剂?1(plasminogen activator inhibitor?1,PAI?1)以及炎症指标肿瘤坏死因子?α(tumor necrosis factor α,TNF?α)、白细胞介素?1β(interleukin?1β,IL?1β)、细胞间黏附分子?1(intercellular adhesion molecule?1,ICAM?1)等的表达情况。结果:与相应的对照组比,腺嘌呤饮食组4周时体重降低,血BUN明显升高,为(41.15 ± 4.59)mmol/L;Ca、P轻度升高,分别为(2.62 ± 0.16)mmol/L、(2.22 ± 0.26)mmol/L(P < 0.05)。腺嘌呤联合高磷饮食组造模4周时血BUN[(14.68 ± 3.57)mmol/L]轻度升高、P[(2.97 ± 0.29)mmol/L]明显升高(P < 0.05),血Ca水平无明显差异。RT?PCR显示腺嘌呤饮食组和腺漂呤联合高磷饮食组小鼠肾脏组织中CollagenⅠ、FN、PAI?1、TNF?α、IL?1β、ICAM?1表达水平均较相应对照组升高。结论:腺嘌呤联合高磷饮食饲喂C57BL/6小鼠4周即可建立高磷血症模型,同时伴有轻度肾功能下降、肾脏纤维化,是制备慢性肾脏病伴高磷血症小鼠模型的可行方法。
英文摘要:
      Objective: By adjusting the phosphorus content in adenine diet,we aimed to establish an effective chronic kidney disease mice model accompanied by hyperphosphatemia for further studies. Methods:Male C57BL/6 mice were divided into four groups:simple adenine dietary:the normal group(1.0% calcium,0.6% phosphorus),the simple adenine group(0.2% adenine,1.0% calcium,0.6% phosphorus),adenine integrating high phosphorus dietary:the normal group(0.8% calcium,0.6% phosphorus),the adenine integrating high phosphorus dietary group(0.2% adenine,0.6% calcium,1.0% phosphorus)(n=7). The weight,the levels of blood urea nitrogen(BUN),calcium(Ca)and phosphorus(P)in serum were measured at 0 and 4 weeks after the start of adenine diet. The gene expression of fibrosis markers collagenⅠ,fibronectin(FN),plasminogen activator inhibitor?1(PAI?1),in?ammatory markers TNF?α,IL?1β and ICAM?1 in the kidney were detected by RT?PCR. Results:Compared to the control group,their bodyweights were decreased and the serum BUN level[(41.15 ± 4.59)mmol/L]was significantly increased at 4 weeks in the simple adenine group,while the levels of serum Ca[2.62 ± 0.16)mmol/L]and P[(2.22 ± 0.26)mmol/L]were slightly increased(P < 0.05). In the adenine integrating high phosphorus dietary group,their weights were reduced and the level of serum P[(2.97 ± 0.29)mmol/L]showed significant increase,whereas the level of serum BUN[(14.68 ± 3.57)mmol/L]were slightly increased at 4 weeks(P < 0.05). There was no significant difference in serum Ca levels. RT?PCR results showed that the expressions of collagenⅠ,FN,PAI?1,TNF?α,IL?1β and ICAM?1 were increased in two model groups. Conclusion:Adenine combined with high phosphorus diet feeding C57BL/6 mice for 4 weeks can establish a hyperphosphatemia model,accompanied by mild renal dysfunction and renal fibrosis,which is an effective method to set up the mice with hyperphosphatemia.
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