Study On The Effect And Mechanism Of Tcm Herb Enema On Intestinal Mechanical Barrier In Non-dialysis CKD 3?5 Patients Based On“Gut-kidney Axis” Theory

Objective:1.Through the TCMISS,this paper summarizes the characteristics and rules of the existing herb enema in the treatment of CKD,and establishes a new herb enema prescription combined with the etiology,pathogenesis and treatment of CKD.2.Based on the“ Gut-Kidney Axis ” theory,the effect of the new herb enema prescription on intestinal mechanical barrier and micro-inflammation in Non-dialysis CKD3?5 patients was observed,and the potential therapeutic efficacy and safety of this prescription in the treatment of CKD were evaluated.3.To observe the intervention effect of the new herb enema prescription drug-containing serum on the inflammation model of human colonic epithelial cells and to study the mechanism of protecting intestinal mechanical barrier.Methods:1.Data mining.Using CNKI,Wanfang data,VIP,CBM and Pub Med database,we searched the literature on herb enema for CKD before December 31,2019,screened and summarized the enema prescriptions in the literatures,and obtained the medication characteristics,prescription rules and new prescription combination of CKD herb enema prescription through the analysis of TCMISS v2.5 software,then to establish a new herb enema prescription.2.Clinical rials.In a randomized,single-blind,placebo-controlled trial,116 patients with non-dialysis in stage CKD3?5 were randomly divided into Placebo Enema Group(n=58)and Herb Enema Group(n=58).The two groups were treated with basic western medicine plus placebo/herb enema.The enema was retained for 1 hour each time,twice in the morning and evening every day,5 days a week,and the course of treatment was 4 weeks.The intestinal mechanical barrier function(endotoxin,D-lac),inflammatory state(CRP,IL-6,TNF-?),intestinal uremic toxin(IS),TCM symptom grading and PAC-SYM score were detected in the two groups before and after treatment.3.Cell experiment.40 SPF SD rats were randomly divided into Blank Group(n=10),Low-dose Herb Enema Group(n=10),Medium-dose Herb Enema Group(n=10)and High-dose Herb Enema Group(n=10).The Blank Group was not given enema,and the low,middle and high-dose groups were given 0.4m L,0.8m L and 1.6m L herb enema at 1:2:4,each time for 30 minutes,twice a day in the morning and evening for 5 days.One hour after the last enema,blood was taken from the abdominal aorta,and the upper serum was collected after centrifugation.Human normal colonic epithelial cells(NCM460)were divided into Blank Group,Model Group,Low-dose Herb Enema Serum Group,Medium-dose Herb Enema Serum Group and High-dose Herb Enema Serum Group.Except for the Blank Group,the other groups were treated with 100?g/m L to induce cell inflammatory injury.The enema serum group replaced the cell culture medium with 10% drug-containing serum,and the Model Group was added with rat serum of the Blank Group.After incubation for 24 hours,the Claudin-1,Occludin,ZO-1,cell OD value,IL-6 and TNF-? were detected in each group.Results:1.Data mining.(1)CKD herb enema prescription used more than 10 times of 23 traditional Chinese medicine,mainly cold and bitter,the efficacy is divided into astringent,heat-clearing and detoxification,diarrhea and accumulation,activating blood stasis,invigorating spleen and replenishing qi,tonifying fire and helping yang,cooling blood and stopping blood,invigorating spleen and dampness.(2)The most commonly used drug combination of CKD herb enema prescription is:rhubarb-calcined oyster,the core drugs are: rhubarb,astragalus,calcined oyster,dandelion,salvia miltiorrhiza,aconite.The Jianpi Yishen Xiezhuo decoction was established with these six herbs.2.Clinical rials.(1)Compared with placebo enema,herb enema can reduce the level of endotoxin,but has no effect on the level of D-Lac.(2)Compared with placebo enema,herb enema could reduce the levels of CRP and IL-6,but had no effect on the level of TNF-?.(3)Herb enema had no effect on the level of IS.(4)Compared with placebo enema,herb enema can reduce the quantitative score of TCM symptoms.(5)The longer the course of herb enema,the lower the compliance of treatment.3.Cell experiment.(1)Compared with the intervention of blank serum,the drug-containing serum of herb enema could enhance the OD value of inflammatory injured cells,but there was no difference among different doses.(2)Compared with the blank serum intervention,the drug-containing serum of herb enema could reduce the levels of IL-6 and TNF-? in the supernatant of inflammatory injured cells,and the effect of high dose is more significant.(3)Compared with the blank serum intervention,the drug-containing serum of herb enema can increase the relative expression of Claudin-1,Occludin and ZO-1 of inflammatory injured cells,and the effect of high dose is more significant.Conclusion:Jianpi Yishen Xiezhuo decoction(rhubarb,astragalus,calcined oyster,dandelion,salvia miltiorrhiza,aconite)enema can protect the intestinal barrier function,reduce microinflammation and relieve clinical symptoms in non-dialysis patients in CKD3?5stage.This effect may be related to the enhancement of intestinal epithelial cell activity,increase the expression of tight junction-related proteins between intestinal epithelial cells,and promote the repair of intestinal mechanical barrier.