伴蛋白结合毒素升高尿毒症模型的建立

doi:10.3969/j.issn.1006-298X.2020.01.007

肾脏病与透析肾移植杂志

伴蛋白结合毒素升高尿毒症模型的建立

出版日期:2020-02-28 发布日期:2020-03-19

A model of uremia with high levels of proteinbound uremic toxins in pigs

Online:2020-02-28 Published:2020-03-19

摘要/Abstract

摘要： 目的：建立伴高浓度蛋白结合毒素的猪尿毒症模型，观察相关生物学参数在3个月内的变化趋势。
方法：实验第1天、第3天用关木通提取物（马兜铃酸A含量为102%）15 g/kg·d给猪灌胃，引起猪急性肾损伤。并于实验第4天、第8天、第10天、第12天，给予吲哚酚50 mg/kg·d和对甲酚100 mg/kg·d 灌胃。检测相关生物学指标，进行组织形态学观察。
结果：（1）早期（第1～20天）：血清肌酐（SCr）和血尿素氮（BUN)急剧升高，约第8～15天左右达高峰，峰值水平约为基础水平的129倍（P＜001）和99倍 (P=0011)，同时伴有一过性的血尿、蛋白尿和持续的肾小管损伤表现（尿NAG和尿糖升高），硫酸吲哚酚(IS)和硫酸对甲酚（PCS）在第4天升至基础水平的65倍（P＜001）和22倍（P＜005），经4次吲哚酚和对甲酚灌胃后，两者进一步升至基础水平的733倍和89倍 (P均＜005)；(2)中期（第20～45天）：SCr 、BUN、IS和PCS水平达峰后下降；（3）晚期（第45～90天）：肾功能衰竭相对稳定期，SCr和BUN分别稳定在基础水平的62倍和51倍左右（P均＜005），IS和PCS分别稳定在基础水平的125倍和38倍左右（P均＜005）；（4）模型动物还出现血红蛋白降低（P＜005），同型半胱氨酸轻度升高（P＜005）等改变；（5）组织形态学改变：第1月和第3月末均表现为肾小管扩张及间质胶原纤维增生，并以第3月末病变更明显。
结论：关木通提取物联合吲哚酚、对甲酚灌胃的方法可快速建立伴高浓度蛋白结合毒素的猪尿毒症模型，可用于今后血液净化域对蛋白结合毒素清除方面的研究。

关键词: 关木通, 蛋白结合毒素, 尿毒症

Abstract: Ｏｂｊｅｃｔｉｖｅ：To establish a model of uremia in pigs with high levels of proteinbound uremic toxins and observe the variation trend of relevant biological parameters in 3 months.
Ｍｅｔｈｏｄｏｌｏｇｙ：A dose of 15 g/kg·d Aristolochia manshuriensis Kom (AMK) extraction was administrated to pigs by gavage on the 1st day and 3rd day,causing acute renal injury in pigs.Subsequently,on the 4th,8th,10 th and 12th days,indoxyl and pcresol were given to pigs by gavage at 50 mg/kg·d and 100 mg/kg·d,respectively.During the experiment,relevant biological parameters were detect continuously,and pathological examinations were performed.
Ｒｅｓｕｌｔｓ：(1) Early stage(120d): serum creatinine (SCr) and blood urea nitrogen (BUN) sharp increased，and reached the peak level to approximately 129 times(P＜001) and 99 times of the basic level (P=0011) at 815d,,together with transient proteinuria,hematuria and persistent renal tubular injury(such as urinary NAG and urinary glucose rising),indoxyl sulfate (IS) and pcresol sulfate（PCS）increased to 65 times(P＜001) and 22 times（P＜005）of the basic level on the 4th day，and further increased to 733 times and 89 times of the basic level after 4 times of indoxyl and pcresol gavage,respectively (both P<005).(2) Medium stage (2045d):characterized by partial recovery of renal function and decreased SCr,BUN,IS and PCS after reaching the peak level. (3) Late stage (4590d),there was relatively stable renal failure stage.SCr and BUN were stabilized at 62 times and 51 times of the basic level,respectively (both P<005); IS and PCS were stabilized at 125 times and 38 times of the basic level,respectively (both P<005). (4)Anemia and hyperhemocysteinemia were also observed.(5) Renal pathological investigation showed residual tubular dilatation and interstitial collagen fiber hyperplasia 1mon after modeling,and 3mon later the lesions was more significant.
Ｃｏｎｃｌｕｓｉｏｎ：The method of AMK extraction combined with indoxyl and pcresol by gavage can quickly establish uremic model with high levels of proteinbound uremic toxins in pigs,which can be used in blood purification of proteinbound uremic toxins clearance for future research.

张冬,任宏伟,李川,孔凌,龚德华. 伴蛋白结合毒素升高尿毒症模型的建立[J]. 肾脏病与透析肾移植杂志, DOI: 10.3969/j.issn.1006-298X.2020.01.007.

ZHANG Dong1,REN Hongwei,LI Chuan，KONG Lin，GONG Dehua. A model of uremia with high levels of proteinbound uremic toxins in pigs[J]. Chinese Journal of Nephrology, Dialysis & Transplantation, DOI: 10.3969/j.issn.1006-298X.2020.01.007.

[1]	古晓燕,龚德华. 血液净化清除蛋白结合毒素的研究进展[J]. 肾脏病与透析肾移植杂志, 2020, 29(3): 280-284.
[2]	杨璨粼,刘玉秋,张晓良. 透析患者钙化防御的治疗[J]. 肾脏病与透析肾移植杂志, 2019, 28(6): 580-585.
[3]	魏萌,梁珊珊,王萌,等. 尿毒症大鼠肠道屏障功能紊乱与微炎症的关系[J]. 肾脏病与透析肾移植杂志, 2019, 28(5): 441-445.
[4]	刘玉秋,杨璨粼,汤日宁,等. 《钙性尿毒症性小动脉病》后续报道[J]. 肾脏病与透析肾移植杂志, 2019, 28(3): 291-292.
[5]	孙凌霜，刘华，梁珊珊，等. 益生菌改善尿毒症大鼠肠道巨噬细胞介导的细菌移位[J]. 肾脏病与透析肾移植杂志, 2019, 28(1): 30-35.
[6]	孙迎香,张明,马雪英,等. 尿毒症脑病磁共振诊断研究进展[J]. 肾脏病与透析肾移植杂志, 2019, 28(1): 58-62.
[7]	周蕾，龚德华. 蛋白结合毒素与心血管疾病[J]. 肾脏病与透析肾移植杂志, 2018, 27(3): 279-283.
[8]	刘玉秋，张晓良，汤日宁，等. 钙性尿毒症性小动脉病[J]. 肾脏病与透析肾移植杂志, 2018, 27(3): 294-299.
[9]	曾玲玲，胡章学. 透析患者皮肤瘙痒的药物治疗[J]. 肾脏病与透析肾移植杂志, 2017, 26(3): 277-281.
[10]	任红旗\|龚德华. 尿毒症肌少症的发病机制和治疗[J]. 肾脏病与透析肾移植杂志, 2015, 24(2): 181-185.
[11]	袁丽萍\|曾海鸥\|林茴\|等. 血液透析患者人工血管移植动静脉内瘘术[J]. 肾脏病与透析肾移植杂志, 2014, 23(5): 443-446.
[12]	杨蕾\|冯胜\|石永兵. 辅助性腹膜透析的临床应用[J]. 肾脏病与透析肾移植杂志, 2014, 23(3): 275-278.
[13]	邬步云，季大玺. 高截留量血液透析临床应用进展[J]. 肾脏病与透析肾移植杂志, 2012, 21(4): 379-383.
[14]	张新天, 庄守纲. 夜间透析的临床应用[J]. 肾脏病与透析肾移植杂志, 2012, 21(2): 179-182.

ISSN 1006-298X CN 32-1425/R

伴蛋白结合毒素升高尿毒症模型的建立

A model of uremia with high levels of proteinbound uremic toxins in pigs

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