Effects of Couplet Medicine of Rheum palmatum -Salvia miltiorrhiza on Enterogenous Urotoxins Contents and Intestinal Barrier Function in Rats with Chronic Renal Failure
- VernacularTitle:大黄-丹参药对对慢性肾衰竭模型大鼠肠源性尿毒素含量和肠道屏障功能的影响
- Author:
Hong WANG
1
;
Juan XU
2
;
Qian JIANG
1
;
Li KANG
1
;
Weiwei LIU
1
;
Ling YUAN
1
;
Xiaoxue CUI
1
;
Linna LIU
2
;
Renrui FENG
1
;
Lei WANG
1
;
Yanlin LI
2
Author Information
1. Cardiovascular and Cerebrovascular Drug Research Laboratory，Tianjin Institute of Medical & Pharmaceutical Sciences，Tianjin 300020，China
2. Dept. Nephrology，Zhongshan Hospital of TCM，Guangdong Zhongshan 528401，China
- Publication Type:Journal Article
- Keywords:
Rheum palmatum;
Salvia miltiorrhiza;
Chronic renal failure;
Enterogenous urotoxins;
Intestinal barrier;
Rats
- From:
China Pharmacy
2021;32(7):825-831
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To study the effects of couplet medicine of Rheum p almatum-Salvia miltiorrhiza on the contents of enterogenous urotoxin and intestinal barrier function in chronic renal failure （CRF）model rats. METHODS ：Totally 55 male Wistar rats were randomly divided into sham operation group （10 rats）and modeling group （45 rats）. In sham operation group ，the kidneys were isolated but not removed ；CRF model was reproduced by 5/6 nephrectomy in modeling group. After modeling （excluding 5 dead and non-modeling rats ），modeling rats were divided into model group （water），Niaoduqing granules group （2.5 g/kg），couplet medicine of R. palmatum -S. miltiorrhiza groups（6，3 g/kg，by crude drug ），with 10 rats in each group. Sham operation group and model group were given constant volume of water intragastrically. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 12 weeks. After last administration ，the contents of creatinine （Scr）and urea nitrogen（BUN）in serum ，the content of urinary creatinine （Ucr） in urine were determined by automatic biochemical analyzer；creatinine clearance rate （Ccr）was calculated. The contents of enterogenous urotoxin [trimethylamine-N-oxide （TMAO），indoxyl sulfate （IS）and p-cresyl sulphate （PCS）] were determined by UPLC-ESI-MS/MS. Real-time RT-PCR and immunofluorescence assay were used to detect the mRNA and protein expression of Occludin and ZO-1 in the ileum tissue. HE staining and Masson staining were used to observe the pathologi cal changes of renal tissue. The ultrastructural changes of rat colon were observed by transmission electron microscope. RESULTS ：Compared with sham operation group ，serum contents of Scr，BUN，TMAO，PCS and IS were increased significantly in model group （P＜0.01），while urine content of Ucr ，Ccr，mRNA and protein expression of Occludin and ZO- 1 in ileum tissue were decreased significantly （P＜0.01）；renal glomerulosclerosis ， renal tubules dilation and inflammatory invasion and fibrosisin the interstitium were all found ；the intestinal epithelial barrier structure of colon tissue was severely damaged. Compared with model group ，serum contents of Scr ，BUN，TMAO，PCS and IS were decreased significantly in administration groups （P＜0.05 or P＜0.01）；the mRNA and protein expression of Occludin and ZO-1 in the ileum tissue were increased significantly （except for mRNA expression of ZO- 1 in R. palmatum -S. miltiorrhiza low-dose group （P＜0.05 or P＜0.01）；the infiltration of inflammatory cells in renal interstitium ，the degree of fibrosis and the damage of intestinal epithelial barrier structure in colon tissue were reduced. CONCLUSIONS ：Couplet medicine of R. palmatum -S. miltiorrhiza can effectively protect the residual renal function of CRF model rats ，the mechanism of which may be associated with reducing the serum contents of enterogenous urotoxin ，up-regulating mRNA and protein expresssion of Occludin and ZO- 1 in the ileum tissue so as to improve intestinal barrier function.
