The Effect Of Compound Traditional Chinese Medicine Combined With Probiotics On Chronic Kidney Disease

Objective: To observe the effect of shenwei herbal medicine compound on chronic kidney disease.To explore the effect and possible mechanism of shenwei herbal medicine compound combined with probiotics in preventing and repairing intestinal mucosal barrierrenal and renal function.Methods: Fifty sprague dawley(SD)rats were randomly divided into five groups,which were Nor group,CKD group,Prob group,SWF group and Prob+SWF group.Besides Nor group,all rats in the rest groups were intravenously injected with adriamycin(4mg/kg)only once and received adenine(200mg/kg/d)by gavage for four weeks to establish CKD model.After the model established,rats in Prob group,SWF group and Prob+SWF group were received respectively probiotic preparations(bifid triple viable tablet,20mg/kg/d),shenwei herbal medicine compound(5.2mg/kg/d)and shenwei herbal medicine compound(5.2mg/kg/d)combined with probiotics(20mg/kg/d)for four weeks.And equal volume of saline was intragastric in the model group and control group.All rats were sacrificed at 4w post medicine intervention,determination of serum creatinine,blood urea nitrogen,24-hours urinary protein level were tested by automatic biochemical analyzer.Limulus reagent chromogenic azo matrixmethod was used to detect endotoxin and ELISA method was adopted for the determination of IL-6,TNF-a and plasma D-lactic acid level.Kidney tissues were harvested for HE and Masson staining.The expression of TGF-?1 of kidney tissue was assessed with immunohistological staining.The intestine tissues were harvested for HE staining and TJ ultrastructure was observed by transmission electron microscopy.Expression and location of TJ protein Occludin in the epithelium were investigated by immunofluorescence microscopy.Expression of CD4+T lymphocytes and CD8+T lymphocytes in intestinal mucosa were assessed with immunohistochemical staining.Results:(1)The index of renal structure and function revealed : The serum creatinine,blood urea nitrogen,24-hours urinary protein level,pathological scoring of renal injury,renal interstitial fibrosis relative area ratio and mean optic density of TGF-?1 in CKD group were all significantly higher than Nor group(P<0.01).All index of renal structure and function in Prob group were lower than CKD group,but had no statistical significance.Compared with CKD group,those index in Prob+SWF group were significantly lower.Among the three treatment groups,index of renal structure and function in Prob+SWF group were both significantly lower than Prob group and SWF group(P<0.05).(2)The index of mucosa barrier and permeability revealed:The morphology of villous was normal in Nor group,but the intestinal villi were in a mess and severe edema,necrotic epithelium,inflammatory cell infiltration and damage of tight junctions were observed in CKD group.The pathological score of intestinal tissue and plasma D-lactic acid level in CKD group were both significantly higher than Nor group(P<0.01).Compared with CKD group,the pathological score and D-lactic acid level in SWF group were lower while with no statistical significance,and Prob+SWF group were significantly lower than CKD group(P<0.05).Among the three treatment groups,the pathological score and D-lactic acid level in Prob+SWF group were all significantly lower than both Prob group and SWF group(P<0.05).The tight junction protein Occludin uniformly distributed in the intestinal epithelial cells at the top of the junction in Nor group.In CKD group,the fluorescence of Occludin protein were reduced,weaker and uneven.Compared with the CKD group,the distortion of tight junction morphology and redistribution of TJ protein Occludin were both prevented in Prob+SWF group.(3)The index of systemic inflammation and intestinal mucosal immune revealed:The plasma endotoxin,serum IL-6 and TNF-a level in CKD group were all significantly higher than Nor group(P<0.01).Those indexes in three treatment groups were all significantly lower(P<0.05)compared with CKD group.Among the three treatment groups,the plasma endotoxin,serum IL-6 and TNF-a level in Prob+SWF group were all significantly lower than both Prob group and SWF group(P<0.05).The immunohistochemical stainingrevealed the intestinal CD4+T lymphocyte percentage in CKD group decreased significantly and CD8+T lymphocyte percentage were significantly ascended compared with Nor group(P<0.01).Compared with CKD group,the intestinal CD4+T lymphocyte and CD8+T lymphocyte percentage in Prob group and Prob+SWF group had both significantly differences.Among the three treatment groups,the CD4+T lymphocyte and CD8+T lymphocyte percentage of the mucosa in Prob+SWF group all had significantly differences with both Prob group and SWF group(P<0.05).Conclusions:(1)Shenwei herbal medicine compound could improve the renal function of CKD rats.(2)Shenwei herbal medicine compound combined probiotics could obviously improve the renal function,which had better effect than single Shenwei herbal medicine compound treatment.(3)Shenwei herbal medicine compound combined probiotics could obviously improve the structure and function of intestinal mucosal barrier,which had better effect than single probiotic treatment.(4)Shenwei herbal medicine compound combined probiotics could obviously improve the structure and function of kidney in CKD rats,which might be related with regulating of mucosal immunity,repairing damaged intestinal mucosa and relieving the inflammatory system.