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。
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 1 st day and 3 rd day,causing acute renal injury in pigs.Subsequently,on the 4 th,8 th,10 th and 12 th 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(1-20 d): 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 8-15 d,,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 4 th 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(20-45 d):characterized by partial recovery of renal function and decreased SCr,BUN,IS and PCS after reaching the peak level.(3) Late stage(45-90 d),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 1 mon after modeling,and 3 mon 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-b
作者
张冬
任宏伟
李川
孔凌
龚德华
ZHANG Dong;REN Hongwei;LI Chuan;KONG Lin;GONG Dehua(National Clinical Research Center of Kidney Diseases,Jinling Hospital,Nanjing University School of Medicine,Nanjing 210016,China;Department of Anesthesiology,Jinling Hospital,Nanjing University School of Medicine,Nanjing 210016,China)
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
北大核心
2020年第1期36-41,共6页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
国家重点研发计划课题(2017YFC1104404)。
关键词
关木通
蛋白结合毒素
尿毒症
Aristolochia manshuriensis Kom
protein-bound uremic toxins
uremia
