| ObjectiveTo observe the effect of oral administration of Bupi Yishen Decoction combined with colon dialysis with renal failure enema prescription on chronic kidney disease stage 5 patients and renal failure rats with intestinal bacteria and intestinal barrier function, and the effect of down-regulating metabolic toxin levels,to evaluate the clinical and animals’therapeutic effects of invigorating the spleen and kidney and eliminating the turbid on chronic kidney disease stage 5, and to further explore the related mechanism for delaying the progression of chronic renal failure through the method of invigorating the spleen and kidney and eliminating the turbid by purgation.MethodsDesigned clinical study and animal experiment.78 outpatient or hospitalization patients of the spleen kidney qi(Yang) deficiency, damp turbidity (damp-heat) and blood stasis type from Nephrology Department were enrolled in this prospective non randomized clinical study in the period from 2013 March to 2014 December. After 11 of them were excluded by criteria, others were grouped according to their own willingness to accept the basic treatment of Western Medicine, the oral administration of Bupi Yishen Decoction, and the colon dialysis therapy with renal failure enema prescription or not, divided into the control group and treatment group.62 cases (30 cases in control group,32 cases in treatment group) actually completed the research, and 5 cases exit. All the patients in the two groups were given the standard basic treatment of Western Medicine;The control group daily with Bupi Yishen Decoction treatment, except that patients in treatment group were additionally treated with colon dialysis therapy with renal failure enema prescription for 8 weeks. Variances on clinical symptoms, metabolic toxin levels (serum creatinine , urea nitrogen, uric acid, indoxyl sulfate), intestinal bacteria (Escherichia coli, Enterococcus, total Anaerobic bacteria, Bif idobacterium, Lactobacillus), intestinal barrier function (plasma D-lactate, plasma endotoxin) and renal function(glomerular filtration rate) were observed and recorded before and after treatment. Animal experiment was used 24 rats divided into sham operation group, model group, oral medicine group, oral medicine+enema group,6 rats in each group, after a total of 8 weeks to die in order to detect the level of metabolic toxins, five gut bacteria and intestinal barrier function related indicators D-lactate and endotoxin levels. Therefore, evaluating the clinical and animals’therapeutic effects, and to further explore the related mechanism for delaying the progression of chronic renal failure through the method of invigorating the spleen and kidney and eliminating the turbid by purgation.Results1. Clinical research:(1) There were no statistical significance at baseline of two groups in gender, age, primary disease, the course of the disease, blood pressure and the use of Proprietary Chinese Medicine (P>0.05).(2) There were no significant differences in comparison of the baseline on TCM symptom scores, glomerular filtration rate, metabolic toxins, intestinal bacteria, endotoxin and D-lactic acid before treatment between two groups (P >0.05).(3) Comparison of TCM clinical symptom scores before and after treatment in two groups:(1)After treatment the total symptom score of the two groups were significantly improved compared with the same group before treatment (P<0.01), but after treatment the total symptom scores of two groups had no significant difference (P>0.05). ②In the control group, the soreness of waist and knee, aversion to cold, dry mouth, bitter taste, nausea and vomiting, cool and more nocturia and dry stool had no significant improvement (P>0.05), the rest of the symptoms were obviously improved(P<0.05 or P<0.01). ③ In the treatment group, the soreness of waist and knee, dry mouth, nausea and vomiting, abdominal distension, cool and more nocturia and loose stool had no significant improvement(P>0.05), while the rest of the symptoms were obviously improved (P<0.05 or P<0.01).④After treatment between the two groups, three symptoms (bitter taste, mouth sticky, dry stool) of the treatment group had obviously better clinical effect than the control group(P<0.05 or P<0.01).⑤ The differen-ce comparison showed that the total symptom score decreased significantly in the treatment group than that in the control group(P<0.05), two symptoms (mouth sticky, dry stool) score of the treatment group decreased significantly than that in the control group(P<0.01).(4) Comparison of metabolic toxin levels before and after treatment in two groups:①The same group compared before and after treatment:After treatment, The blood creatinine, urea nitrogen, uric acid levels of two groups were reduced, the differences were all significant (P<0.01);After treatment the indoxyl sulfate levels of treatment group was decreased significantly(P<0.01) ;while the indoxyl sulfate levels of control group before and after treatment had no significant difference (P>0.05). ②Comparison between two groups after treatment:The blood creatinine, urea nitrogen, uric acid levels of two groups showed no significant difference (P>0.05);while the indoxyl sulfate levels of the treatment group were lower than the control group significantly (P<0.01). ③Difference comparison:The urea nitrogen, uric acid, indoxyl sulfate levels of the treatment group decreased much more than that of control group, with significant difference(P<0.01).(5) Comparison of intestinal flora before and after treatment in two groups:①The same group compared before and after treatment:The Escherichia coli, Enterococcus colony counts of the treatment group were significantly decreased compared with those before treatment (P<0.01), while the total Anaerobic bacteria, Bifidobacterium, Lactobacillus colony counts were increas-ed significantly compared with those before treatment(P<0.01);The Escheri-chia coli colony count of control group significantly decreased compared with those before treatment (P<0.01), with no significant difference of Enterococcus colony count(P>0.05), while the total Anaerobic bacteria, lactic acid bacteria were increased significantly compared with those before treatment (P<0.01 or P<0.05), no significant difference of Bifidobacterium colony count(P>0.05). ②Comparison between two groups after treatment:Escherichia coli colony count of the treatment group decreased significantly compared with the control group(P<0.05), there were no significant differences of Enterococcus colony count (P>0.05);the total Anaerobic bacteria, Bifidobacterium, Lactobacillus colony counts of the treatment group were significantly increased compared with the control group (P<0.01). ③ifference comparison:The Escherichia coli, Enterococcus colony count decreased and the total anaerobic bacteria, Bifido-bacterium, Lactobacillus colony count increased in the treatment group much more than that in the control group, both with significant difference (P<0.01).(6) Comparison of the intestinal barrier function of two groups before and after treatment:① The same group compared before and after treatment: D-lactic acid, endotoxin levels in the two groups were all significantly decreased than before treatment (P<0.01). ②Comparison between two groups after treatment:D-lactic acid levels of the treatment group decreased significantly compared with the control group (P<0.01), the levels of endotoxin had no significant difference compared with the control group(P>0.05). ③Difference comparison:The D-lactic acid, endotoxin levels of the treatment group decreas-ed more than the control group, with significant difference(P<0.01 or 0.05).(7) Comparison of renal function before and after treatment in two groups:After treatment eGFR levels were significantly increased than before treatment in the same group(P<0.01);After treatment eGFR levels had no significant difference between two groups(P>0.05);About difference compare-ison there was no significant difference between two groups(P>0.05).(8) Comparison of clinical efficacy of the two groups:30 cases in the control group,2 cases were cured(6.7%),8 cases were effective (26.7%),10 cases were stable(33.3%),10 cases were invalid(33.3%), the total efficiency was 66.7%;32 cases in the treatment group,4 cases were cured(12.5%),15 cases were effective(46.9%),9 cases were stable(28.1%),4 cases were invalid(12.5%), the total efficiency was 87.5%. The total effective rate of the treatment group increased significantly compared with the control group(p=0.05).(9) Correlation analysis related indicators in clinical study:metabolic toxins indoxyl sulphate and common indicators of renal toxin serum creatinine, blood urea nitrogen, uric acid showed a positive correlation with uric acid-related endotoxin into a positive, indoxyl sulphate was positively correlated with the D-lactic acid, sulfuric acid indoxyl and anaerobic probiotic Lacto-bacillus, Bifidobacterium, total anaerobes showed a negative correlation with aerobic pathogenic E. coli, enterococci showed a positive correlation, and the endotoxin and lactobacilli, total anaerobic Bacteria also negatively correlate-ed, D-lactic acid and probiotic Lactobacillus, Bifidobacterium, total anaero -bes negative correlation, enterococci and lactobacilli.bifidobacteria, total anaerobes negative correlation;total anaerobic bacteria and E. coli, Enteroc-occus negatively correlated negatively correlated Bifidobacterium and Enterococcus;Lactobacillus and Enterococcus negative correlation;and total anaerobic bacteria, lactobacilli, are positively related to E. coli between the three Bifidobacterium, Enterococcus and serum creatinine, blood urea nitrogen, uric acid showed a positive correlation;total anaerobic bacteria, bifidobacte-ria and serum creatinine, blood urea nitrogen, uric acid showed a negative correlation, Lactobacillus negatively correlated with urea nitrogen and total anaerobic bacteria associated with chronic kidney disease age, duration showed some negative.2. Experimental study:(1)Metabolic toxins comparison:Compared with sham operation group, model group, oral group, oral+enema group serum creatinine, blood urea nitrogen, indoxyl sulphate significant differences were statistically significant(P< 0.01),uric acid is only the model group and the sham group was statistically significant(P<0.01);compared with the model group, the oral group and oral+ enema group serum creatinine, blood urea nitrogen, uric acid had a significant difference was statistically significant(P<0.01), sulfuric acid indoxyl only oral+enema with model group was statistically significant(P<0.01);compared with the oral group, oral+enema group serum creatinine, blood urea nitrogen, indoxyl sulphate have significant differences, there was statistically signifi-cant(P<0.01).(2) Intestinal flora comparison:Compared with the sham group, model group of E. coli, Enterococcus, Bifidobacterium, Lactobacillus, total anaerobes have significant differences were statistically significant(P<0.05 or P<0.01); oral group Bifidobacterium, Lactobacillus, total anaerobes with the sham group was statistically significant (P<0.01);oral+enema group E. coli with the sham group was statistically significant (P<0.01); compared with the model group, the only oral+enema group E. coli, Bifidobacterium, Lactobacillus, total anaerobes significant difference was statistically significant(P<0.01);compared with the oral group, oral+enema group of E. coli, Bifidobacterium, Lactobacillus, total anaerobes significant difference was statistically significant(P<0.01 ).(3) Intestinal barrier function comparison:sham group, model group, oral group, oral+enema group D-lactate, endotoxin were significant differenc-es were statistically significant(P<0.01);compared with model group oral group and oral enema group+D-lactate, endotoxin significant difference was statistically significant (P<0.01);compared with the oral group, oral+enema group D-lactate, endotoxin have significant differences, there statistically significant(P<0.01).Conelusion1. "Deficiency of Spleen and Kidney, Retention of Turbidity Toxin in the Interior" is the basic pathogenesis of Traditional Chinese Medicine in chronic renal failure.2. Application of invigorating the Spleen and Kidney and eliminating the Turbid by Purgation to CKD stage 5 had clinical and experimental efficacy, that can improve the clinical symptoms, downregulate metabolic toxin levels espec-ially enterogenous toxin IS levels, improve renal function, thus delay the progress of renal failure in patients with CKD stage 5.3. In improving the clinical symptoms and enhancing the clinical curative effect, the treatment group with the method of eliminating the Turbid by Purgation was better than that of control group, and in the short term significantly improved Turbidity Toxin (Dampness, Damp-Heat) Syndrome of patients compared with the control group, which showed that the application of method with Eliminating the Turbid by Purgation to reduce Turbidity Toxin in the interior is an important treatment method for CKD stage 5, thus as a typical representative of method with Eliminating the Turbid.by Purgation, colon dialysis therapy with Traditional Chinese medicine enema is an important characteristic TCM therapy for the treatment of CKD stage 5.4. The therapeutic mechanism of the method of invigorating the Spleen and Kidney is associated with the strengthening Spleen Chinese Medicine’s roles of regulating intestinal microflora and improving intestinal barrier function , also related with the nourishing Kidney Chinese Medicine’s roles of regulat-ing immunity, inhibiting inflammation and reducing oxidative stress damage effects.5. The therapeutic mechanism of the method of eliminating the Turbid by Purgation is associated with its roles of increasing intestinal metabolic wastes and toxin excretion, regulating intestinal flora and improving intest -inal barrier function, reducing the absorption of endotoxin, or increasing the intestinal probiotics that decompositing and using more nitrogen waste. |
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