Renal Protection And Injury Assessment For Rhubarb Based On Theory Of "YOU GU WU YUN"

Recent years, many reports about adverse reactions of Chinese traditional medicine (TCM) have caused social concerns for security of Chinese medicine and casted a shadow over for Chinese medicine to go into the international. Rheum, is one of the most important traditional Chinese medicine in our country, have been widely used in gastrointestinal disease, hepatitis, nephritis, obesity, etc. But, rhubarb had been argued that it was nephrotoxicity, hepatotoxicity and have potential carcinogenicity by foreign, that made the clinical application safety of rhubarb and some Chinese patent medicine with related be queried.In this study, the theory of "YOU GU WU YUN" was used as a guide, acorrding to the biphasic effect for nephrotoxicity and renal protection of rhubarb, proposed to create the mode and method of rhubarb safety evaluation based on disorder toxicology, a comparative study on normal rats and disease animals (4kinds of ARF rats with different reagents induced), and then, the intervention and law on different extracts of rhubarb to different disease animal models with integrated comparative. The aim of this work is to elucidate the relationship amony "toxicity, effect, material and disease" of therapy for renal failure with rhubarb, to evaluate the objective authenticity for nephrotoxicity and renal protection of rhubarb, its material base and potential mechanism. In order to put forward suggestions for reasonable use of rhubarb in clinic, provide evidence for syndrome differentiation, provide new visual and thought for the enrichment and development of toxic theories of TCM. The study results as follow:1.Preparation for different extracts of rhubarb:The dried rhubarb was extracted with60%ethanol to get the total extract of rhubarb (TR). And then a part of TR was divided into the total anthraquinones (TA) free of tannins, the total tannins (TT) free of anthraquinones, and the remaining components (RC) free of both anthraquinones and tannins using D-101macroporous resin. The yields of each were41.2%,6.73%,26.1%and5.92%. The content of5anthraquinone monomer and total anthraquinones and tannins in each extract was determined by UPLC and UV. The dates show that rhubarb have been well divided.2. The nephrotoxicity evaluation of rhubarb based on normal rats:TR, TA, TT and RC were treated to normal rats according to the3g/kg·d dose to last one week. There were no deaths observed in7days. TR and TA made SUN increase significantly(p<0.05), especially TA increased CREA more(p<0.01) and decreased Na. Renal tubular epithelial cells appear granular degeneration of rats in TR and TA groups.3. The nephrotoxicity and renal protection evaluation of rhubarb based on ARF rats:(1) Comparative study on the effect of each rhubarb extract to renal tubular S1injury in rats:ARF model groups were induced by administered subcutaneously with a single dose of potassium dichromate (20mg/kg) aqueous solution (administraion condition as the same above). Except TT group, the mortality rates of M, TA and RC groups were38%while its50%in TR group. For the four kinds of extracts, only TT can improve the unnormal indexs (SUN, CREA) and the phenomenon of renal tubular epithelial cell necrosis, interstitial vascular dilatation and congestion. TR evently increased CREA and made injury worse. The maximum inhibition rate for·OH of TT was about70%, reduction reaction and precipitation reaction could appear between TT and Cr(Ⅵ).(2) Comparative study on the effect of each rhubarb extract to renal tubular S1, S2injury in rats:ARF model groups were induced by administered subcutaneously with a dose of potassium dichromate (3mg/kg·d) aqueous solution for4days (administraion condition as the same above). There were no deaths observed in7days. Compared to group N, SUN and CREA increased greatly, TR TA TT and RC all could decreased them, especially in CREA. TR appeared the best effect for improving renal injury.(3) Comparative study on the effect of each rhubarb extract to renal tubular S3injury in rats:ARF model groups were induced by administered subcutaneously with a single dose of mercuric chloride (2mg/kg) aqueous solution (administraion condition as the same above). After administration with mercuric chloride, each one rat have been found in TR and TA groups. But, mortality rates of TT and RC groups were50%and62%while that of M group was75%. Compared to rats in M group with the phenomenons about SUN, CREA increased and TP, ALB dcreased whopping, even extensive necrosis of proximal tubular epithelial cells, TR and TA played the role of improving that effectively. But, ascites was appeared in rats with TT-treated and renal ischemia was appeared in RC and M groups.(4) Comparative study on the effect of each rhubarb extract to renal tubular epithelial cells injury in rats:ARF model groups were induced by administered subcutaneously with a dose of gentamicin (2mg/kg) aqueous solution for4days(administraion condition as the same above). During the7days, mortality rates of TR was25%, and there were no death appeared in others. Compared to M group, TA, TT, RC nearly have no effect for SUN and CREA. But, TR increased that (p<0.01). In addition, the K value in TR group was less than that of N group. Furthermore, the phenomenon on renal tubular department membrane cell proliferation appeared worse in rats with TR treatment.4. comprehensive analysis(1) The objective authenticity for nephrotoxicity and renal protection of rhubarb.(2) The material base or nephrotoxicity and renal protection of rhubarb.(3) The usage value of "YOU GU WU YUN" thinking used on toxicity assessment of TCM.Above all, this study shows that the renal injury performance of rhubarb at dose on normal animals, but also showed a therapeutic effect on different renal failure model. So the effects for nephrotoxicity and renal protective of rhubarb is a relative term. It is suggested that the evaluation for "poison" and "efficiency" of TCM should acorrding to body status and the types of diseases. The results of this study have provided an important basis for an objective evaluation to the renal toxicity of rhubarb. The experiments confirmed that syndrome differentiation is scientific and practical, also provided ideas and examples for richment and development on the toxic cognitive theory of TCM with based on "YOU GU WU YUN" thinking.