尿毒康合剂改善慢性肾病大鼠肠源性尿毒素蓄积的研究  

Research on improving accumulation of enterogenous urotoxin in rats with chronic nephropathy by Niaodukang mixture

作　　者：王蕾[1] 徐娟 王宏[1] 江茜 张婷[1] 袁玲[1] 刘琳娜[2] 康利[1] 李燕林[2] WANG Lei;XU Juan;WANG Hong;JIANG Qian;ZHANG Ting;YUAN Ling;LIU Lin-na;KANG Li;LI Yan-lin(Cardiovascular and Cerebrovascular Drug Research Laboratory,Tianjin Institute of Medical&Pharmaceutical Sciences,Tianjin 300020,China;Department of Nephrology,Zhongshan Hospital of Traditional Chinese Medicine,Zhongshan 528401,Guangdong Province,China)

机构地区：[1]天津市医药科学研究所心脑血管药物研究室,天津300020 [2]中山市中医院肾内科,广东中山528401

出　　处：《中国临床药理学杂志》2023年第2期246-250,共5页The Chinese Journal of Clinical Pharmacology

基　　金：广东省自然科学基金资助项目(2017A030313720);广东省中医药局科研基金资助项目(20201372);广东省中医药局专项研究课题基金资助项目(20223020);中山市社会公益科技研究基金资助项目(2018B1008);中山市社会公益与基础研究基金资助项目(2020B3005);天津市卫生健康委员会科技人才培育基金资助项目(KJ20018);中山市社会公益科技研究项目(医疗卫生重点项目)基金资助项目(210904224108136)。

摘　　要：目的 研究尿毒康合剂改善慢性肾病(CKD)大鼠肠道屏障促进肠源性尿毒素代谢作用。方法 用5/6肾切除法复制CKD大鼠模型,假手术组大鼠分离肾组织但不切除。将CKD大鼠分为模型组、对照组和低、中、高剂量实验组,每组10只。假手术组和模型组均给予等体积饮用水;对照组按2.5 g·kg^(-1)剂量给予0.25 g·mL^(-1)浓度尿毒清颗粒;低、中、高剂量实验组分别按5.0,10.0和20.0 mL·kg^(-1)剂量给予尿毒康合剂原液。6组大鼠每天给药1次,连续12周。末次给药后取材,用超高效液相色谱-电喷雾串联三重四级杆质谱法同时测定大鼠血清中尿毒症毒素[氧化三甲胺(TMAO)、硫酸吲哚酚(IS)、硫酸对甲酚(PCS)]的含量,用免疫荧光法检测大鼠回肠组织中闭合蛋白(Occludin)、紧密连接蛋白1(ZO-1)蛋白的表达水平。结果 高剂量实验组、对照组、模型组和假手术组的血清TMAO分别为(0.48±0.04),(0.52±0.56),(2.06±0.34)和(0.22±0.02)μg·mL^(-1),血清IS分别为(2.23±0.23),(2.18±0.26),(10.51±1.52)和(1.48±0.11)μg·mL^(-1),血清PCS分别为(0.46±0.10),(0.24±0.08),(1.06±0.17)和(0.29±0.11)μg·mL^(-1),回肠组织Occludin表达量分别为0.72±0.04,0.70±0.03,0.34±0.02和1.00±0.00,回肠组织ZO-1表达量分别为0.83±0.06,0.76±0.06,0.40±0.05和1.00±0.00。高剂量组和对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.01)。结论 尿毒康合剂能够改善慢性肾病大鼠肠源性尿毒素蓄积的作用。Objective To study the effect of Niaodukang mixture on improving intestinal barrier and promoting enterogenous urotoxin metabolism in rats with chronic kidney disease (CKD).Methods The model of chronic renal failure was made by 5/6 nephrectomy,and the rats in sham-operation group were separated from the renal tissue without nephrectomy.Chronic renal failure model rats were divided into model group,control group and experimental-L,-M,-H groups.The sham-operation group and model group were given equal volume o drinking water.The control group was given 0.25 g·m L-1niaoduqing granules at the dose of 2.5 g·kg^(-1).Experimental-L,-M,-H groups were given the original solution of Niaodukang mixture at the dose of 5.0,10.0 and 20.0 m L·kg^(-1),respectively.The corresponding drugs were given to rats in each administration group once a day for 12weeks.After the last administration,the contents of uremic toxins[trimethylamine oxide (TMAO),indophenol sulfate(IS) and P-cresol sulfate (PCS)]in rat serum were simultaneously determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry.The protein expression levels of Occludin and tight junction protein 1 (ZO-1) in rat ileum were detected by immunofluorescence.Results The serum TMAO of experimentalH,control,model and sham-operation groups were (0.48±0.04),(0.52±0.56),(2.06±0.34) and(0.22±0.02)μg·m L-1;the serum IS were (2.23±0.23),(2.18±0.26),(10.51±1.52) and (1.48±0.11)μg·m L-1;the serum PCS were (0.46±0.10),(0.24±0.08),(1.06±0.17) and (0.29±0.11)μg·m L-1,expression levels of Occludin in rat ileum were 0.72±0.04,0.70±0.03,0.34±0.02 and 1.00±0.00,expression levels of ZO-1 in rat ileum were 0.83±0.06,0.76±0.06,0.40±0.05 and 1.00±0.00.Compared with the model group,the above indexes of the high dose group and the control group were significantly different (all P<0.01).Conclusion Niaodukang mixture can improve the accumulation of enterogenous urotoxin in rats with chronic nephropathy.

关 键 词：尿毒康合剂 肠肾轴 肠源性尿毒素 肠黏膜上皮屏障 慢性肾病 

分 类 号：R28[医药卫生—中药学]