| The spleen-hypofunction diarrhea syndrome is one kind of traditional Chinese medicine syndrome, appeared with general physical symptoms, such as diarrhea, decreasing of body mass, chilly and tired. The disease category is broader, including chronic diarrhea, ulcerative colitis, irritable bowel syndrome, enteron tumor, et al. At present, the drug's effect for this syndrome isn't very well. According to the clinical observation, Chinese formula Fu-Xie-Kang(FXK) has 90% clinical cure rate on splenasthenic diarrhea, by invigorated the spleen, relieved pain, antidarrheaed with astringent. It would be valuable to do mechanism research and widespread popularization on clinic.Etiopathogenisis and nosogenesis of splenasthenic diarrhea are complex. It is difficult to establish animal models which are consistent with this traditional Chinese medicine syndrome for appreciation of new curative drug. So the research of splenasthenic diarrhea animal models is imminently. According to previous literature, we established several kind of models and found the model established by Folium Sennae and acetic acid was the best of all for it was coincidence to clinical characteristic and objective indexes of splenasthenic diarrhea. We can use this model to evaluated pharmacodynamic action of drugs.We evaluated pharmacodynamic action of FXK according to the research manual of new traditional Chinese medicine. FXK had marked preventive and therapeutic effects, such as the immune, digestive and absorptive functions, on rat with splenasthenic diarrhea by degraded the activity of MPO, NOS, iNOS and the level of NO.In order to clarify the mechanism of FXK at molecule level, we used proteomics technique to find changes of protein expression in colon and spleen of splenasthenic diarrhea rat induced by Folium Sennae and acetic acid. It was shown that 5 proteins's expression on splenasthenic diarrhea rat's colon were up-regulated and 5 proteins down-regulated, respectively. These proteins involved Cu/Zn superoxide dismutase and DJ-1 protein which were participated in peroxidatic reaction. Heterogeneous nuclear ribonucleo protein A2/B1 and gelsolin are associated with autoimmunity. Creatine kinase, ATP synthase D chain and voltage-dependent anion channel 2 participate in energy metabolism. Actin is associated with cell apoptosis. Desmin involves in hyperplasia. Hpx protein is associated with blood clotting. 9 proteins's Expression on splenasthenic diarrhea rat's spleen were down-regulated. Those proteins involved proteasome subunit, alpha type 2 which participate in ubiquitin-proteasome mediated proteolysis, Rho, GDP dissociation inhibitor(GDI) alpha, beta, myosin regulatory light chain 2, isoform 1 of tropomyosin 1 alpha chain which are associated with cytokelet dynamics change in cell apoptosis, carbonic anhydrase I , II and Ran protein involved in cell growth and differention. The effect of FXK on reversing the colon and spleen's proteins expression is obvious. It may play the important role by resist oxidative stress, reduced autoimmune response and apoptosis, improved energy metabolism of mitochondrium, regulated ubiquitin-proteasome pathway and growth and differention of cells, et al.In short, we established a spleen-hypofunction diarrhea syndrome model used it to evaluatd the FXK's therapeutic effect on model animals, and then approached the mechanism of FXK with Proteomics technology. The experimental evidence provided valuable reference for the further research... |
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