| Chronic renal failure(CRF)as a chronic non-communicable disease is very common in clinical practice,the cause of the disease is very complex currently,The rate of CRF is increasing year by year,as one of the complications of diabetes,hypertension which is increasing nowdays.there is still no treatment of chronic renal failure which is safe and effective enough.There will be accompanied by a variety of gastrointestinal reactions of CRF patients with different stages:according to Chinese meciicine,the theory of 'kidney-stomach",we select rhubarb and Astragalus Chinese herbal 1edicine as a research object in this subject,both of them are commonly used for the treatment of CRF in clinical,and play a very good therapeutic effect,but has not yet seen the report of mechanism from the aspects of gastrointestinal of CRF.In this study,the CRF rat model was established by mode:m pharmacological experimental method based on the pathogenesis of chronic renal failure and the theory of "kidney-stomach-related".First,we select the optimal dose of rhubarb and astragalus that were used in the treatment of chronic renal failure.Later,different ratio programs were used to study the effects of different proportions of rhubarb and astragalus on the body weight,kidney coefficient,the levels of 24h urinary protein(Proteinuria;Upr),serum creatinine(SCR),blood urea(BUN),urinary acid(UA),gastrointestinal hommone,and the expression of pathway in renal fibrosis related factor,in order to investigate the correlation between gastrointestinal hormone levels and expression of pathway in renal fibrosis related factor,and pharmacological mechanism of different proportions of rhubarb and astragalusin in chronic renal failure.at the same time,screen out the best clinical dosing regimen.Objective:To observe the changes of gastrointestinal motility and the expression of renal fibrosis related factors such as transforming growth factor?1(TGF-?1)?hepatocyte growth factor(HGF);HGF in CRF rats treated with different proportions of rhubarb and astragalus on CRF rats And to analyze the pharmacological mechanism of rhubarb and astragalus in the treatment of chronic renal failure and the best clinical formula.Method:The rat model of CRF was prepared by 5/6 nephrectomy.When it was succ.essful,the rats were divided into model group according to the level of 24h Upr.In the experiment of single herb,the rats in the model group were divided into model group,Benazepril group,rhubarb and astragalus high,middle and low dose group.And in the experiment of rhubarb astragal us membranaceus,it was divided into rhubarb group,astragalus group,rhubarb astragalus membranaeeus 1:1 group,1:2 group,1:4 group and 1:6 group.After 1 week of drug intervention,the animals were sacrificed 5 weeks after the administration.24 hours urine was collected and the levels of serum SCR,BUN and UA were measured in the abdominal aorta In the experiment of rhubarb astragalus membranaceusan addition to the above steps,isolated The antral tissue was isolated and the gastric motility(MTL;Motilin),GAS(GAStrin),Vasoactive intestinal peptide(Vasoactive intestinal peptide)and Sornatostatin(SS)were neasured to detect the expression of TGF-?1,TGF-?1mRNA,HGF,C-Met(hepatocyte growth factor receptor).Result:1.The levels of SCR,BUN and UA in CRF rats were significantly decreased after treatment with single herb rhubarb(P<0.01,P<0.05),astragalus and rhubarb astragalus membranaceus.The levels of rhubarb and rhubarb astragalus 1:4 were significantly higher than those of CRF rats Significant inhibitory effect.2.In the experiment of rhubarb astragalus membranaceus,the expression of TGF-pl in CRF rats was significantly decreased and the expression of C-Met in renal tissue was increased by rhubarb,astragalus and rhubarb astragalus group(P<0.01,P<0.05).Rhubarb astragalus l:2 and l:4 eould decrease the expression of TGF-?1mRNA concentration(P<0.01,P<0.05),rhubarb astragalus 1:2,1:6 group can improve the expression of HGF(P<0.05),with the role of reducing renal interstitial fibrosis.In addition to rhubarb and rhubarb astragalus 1:1 group,the other parties can significantly improve the serum MTL concentration(P<0.01,P<0.05),thubarb and rhubarb astragalus 1:2,1:4,1:6 can reduce the level of serum GAS(P<0.01,P<0.05),rhubarb and rhubarb astragalus can improve serum SS concentration,reduce serum VIP concentration(P<0.01),adjust the level of gastrointestinal hormones in the body,help to restore gastrointestinal motility.3.In the experiment of rhubarb astragalus membranaceus,rhubarb and rhubarb astragalus 1:4 group had significant inhibitory effect on the compensatory hypertrophy of CRF rats.All treatment group can protect the integrity of renal tubular epithelial cell structure effectively,reduce glomerular sclerosis,renal tubular dilatation and renal interstitial fibrosis,inhibit the hyperplasia of renal interstitial inflammatory cells and connective tissue.4.The expression of HGF/C-Met and serum SCR was not significantly correlated with the level of gastrointestinal hormones(P>0.05),the levels of 24h urinary protein,BUN,UA,TGF-?1 and mRNA were significantly correlated with GAS,VIP and SS(P<0.0],P<0.05).not correlated with the content of MTL,and the expression level was positively correlated with the contents of GAS and VIP,and negatively correlated with contents of SS significantly.The efficacy of the 1:2 ratio was optimal in each treatment group.Conclusion:A single herb rhubarb and astragalus can significantly reduce the 24h upr,serum SCR,BUN,UA levels in CRF rats,inhibit the compensatory hypertrophy of residual kidney,improve the pathological state of residual kidney,restore renal function effectively.In the treatment group,the effect of rhubarb middle dose and astragalus medium group was the best.The levels of TGF-?1 and the levels of letabolic toxins,including 24h urinary protein,BUN and UA,were not significantly correlated with HGF/C-Met expression levels in CRF rats.The levels of SCR,BUN and UA in the CRF rats were significantly lower than those in the control group,and the renal hypertrophy of the residual kidney was inhibited.The pathological status of the residual kidney was improved and the expression of TGF-?1/HGF was regulated.Delay the degree of renal interstitial fibrosis,effective recovery of renal function,regulate the level of gastrointestinal hormones,contribute to the recovery of gastrointestinal function.The treatment group of Rhubarb Astragalus 1:2 group was the best. |
PDF Full Text Request