Effect Of Different Routes Of Addition Of Glycyrrhiza Uralensis Fisch And Glycyrrhiza Decoction On "Toxic - Effect" Of Ascites Rats

Background:"Eighteen antagonisms" as the incompatibility of TCM was derived from "Sheng Nong’s herbal classic". It was recorded by doctors of all dynasties which needs pay more cautious in clinical. In terms of its origin, Someone comply with the specification while others believe that using opposing herbal remedies can treat difficult miscellaneous diseases. In recent years research for eighteen antagonisms mainly concentrated in the physiological aspect, and the content was mostly about single drug combination or compound which containing the drug combination. It’s less for the drug combination in the pathological state of action. But the premise of clinical application is pathological state and compound will have to add and subtract medicine to treat disease. So in compound remove one or two taste the medicine will affect the curative effect of compound, if the compound there are side effects, whether the side effects associated with the drug combination is also in doubt. This topic use Kansuibanxia soup as the carrier, pathological ascites model is set up. On the basis of the previous studies, this topic discusses the influence of different medicine mode Kansuibanxia soup subtraction Kansuigancao anti-drug combination for the biological effect of ascites model rats.Purpose:Early research had screened effective and showed no obvious toxicity for further experiment on the basis of Kansui Gancao specific ratio, the dosage and processing varieties. Compare the Kansui decoction and Kansui powder which two kinds of medicine mode Kansuibanxia soup all party group with blindly against drug or two against drug compared with corresponding whole party group, observe its effect on ascites model rats. Further investigation has been did with Kansuigancao anti-drug combination of Kansuibanxia soup which performing "poison" and "effect" is associated with the drug combination. To Rich and perfect the theory of "eighteen antagonisms" as well as to guide the clinician safety and reasonable use of Kansuigancao anti-drug combination to provide scientific support.Method:This topic wheih have already carried on the preliminary experiment research of using method of Kansui. Explore the Kansui decoction and Kansui powder, two kinds of medicine mode which effect the biological of cancerous ascites model rats in experimental research. It is the experiment that have designed four main processing varieties which is unprocessed Kansui, processed Kansui, unprocessed Kancao, processed Kangancao, and they’re compatibility combination. And finally argue the effect on different drug-delivery way under the same processing varieties. Then we did all categories between the longitudinal comparison. And draw a conclusion:No matter which drug-delivery way, it can promote diuresis. Of all the processing varieties, Kansuibanxia soup with processed Gancao and unprocessed Kansui which has the better promoting diuresis. But the group with unprocessed Kansui powder may have further injury for the immune organ. For a large amount of ascites due to liver and kidney damage the party group of decoction may have certain protective effect.Results:Under the different drug-delivery way, the biological effect and mechanism of Kansuibanxia soup add or subtract Kansuigancao anti-drug combination on rats with ascites(1)Toxicity CharacterizationCardiac function:The different drug-delivery way of the whole party group and the separated prescriptions did not show obvious toxicity and efficacy in terms of lower rat cardiac index. In terms of reduce rat CK,Kansui decoction party group, Kansui decoction party group subtract Gancao, Kansui powder party group which compares with the blank group CK reduced statistically significant(P<0.05). But compared with model group, each dose group had no statistical difference (P>0.05). So in terms of rats CK levels to medicine group did not show obvious toxicity and efficacy. Compared with blank group. Kansui decoction party group, party group subtract Kansui, party group subtract Gancao and Kansui, which have higher contents of LDH was statistically difference (P<0.05). The rest of the dosage group compared with the blank group has a rising trend. And compared with model group positive medicine group, party group subtract Gancao, Kansui decoction party group,, Kansui powder party group subtract Gancao, which the LDH has a reducing trend. The group above may show some efficacy. In tenns of heart pathological tissue morphological, Compared with model group the Kansui decoction party group shows less pathological changes.Liver function:In terms of improve liver function, including lower rat AST, ALT, ALP, AST/ALT, GLB, and elevate TP.ALB, Overall.the role of Kansui decoction party group has a certain advantages than Kansui decoction party group., but has not statistically difference (P>0.05). To sum up, the whole party group has a better liver function improvement than separated prescriptions. In terms of improving liver antioxidant indicators such as SOD, MDA, GSH effect of the Kansui decoction party group is better than that of Kansui powder party group. And the whole party group has a better improvement of antioxidant indicators than separated prescriptions.Renal function:In terms of lower rat kidney index, compared with model group under the different drug-delivery way Kansuibanxia soup add or subtract Kansuigancao anti-drug combination showed lower role, with statistical difference (P<0.01), but no significant statistical difference between each dose group (P>0.05).It is prompted that the dosage could improve the group but no difference between each other. In rat serum levels of BUN and CRE, model group and each dosage group compared with the blank group had no statistical difference (p> 0.05). Compared with model group. Kansui powder party group, Kansui powder party group subtract Gancao, the whole party subtract Gancao and Kansui, which has the effect to reduce the CRE, statistically difference. The rest to medicine group and model group compare CRE, had a tendency to reduce, Kansui powder party group has the improvement effect on BUN and CRE than Kansui powder party group which has a slight advantage. Compared with the whole party, the separated prescriptions has less renal function improvement.(2) Efficacy evaluationDiuresis effects:The different drug-delivery way of the whole party group shows the effects on increase in body weight of rats, decrease abdominal circumference, increase the amount of urine and reduce the amount of ascites, increase the serum K. and reduce the amount of serum Na and ADH. Kansui powder party group In this regard is relatively weak. While, the potassium ions in the blood and urine results showed that high potassium symptoms, in this regard may exhibit certain toxicity. And the whole party removed one or two anti-drug compared with the Kansui decoction party group has a relatively poor effect in promote diuresis. And the whole party removed one or two anti-drug compared with t Kansui decoction party group played a certain role to improve in terms of lower potassium.Immunomodulatory:The different drug-delivery way of the whole party group have immune regulating of improvement, especially in cancers of the rats, spleen reactive hyperplasia showed certain positive effect. All party group in stimulating IFN-y secretes also showed a certain regulation, but no obvious difference. The whole party removed one or two anti-drug also performed a role in improve spleen proliferation response. But the increased t expression of TNF-a showed certain toxicity. Analysis of the reason may be due to the large number of secretion of the TNF-a with the role of tumor angiogenesis form, thus inhibiting the growth of VEGF. In conclusion that Kansui decoction party group be superior to the whole party removed one or two anti-drug in immune regulation performance.(3) MechanismLiver:The whole party group and the whole party removed one or two anti-drug group under the different drug-delivery way both have the effect on the expression of rat liver CYP2E1 mRNA. And the hole party group has Increased significantly. So that Kansui-Gancao compatibility combination can induce the CYP2E1 mRNA expression. Compared with the model group each dosage group has a significant rise in CYP3A1 mRNA and CYP3A2mRNA expression. Increasing toxicity metabolism, which reducing the toxic effects of the liver in turn. Compared with Kansui decoction party group, Kansui powder party group has a lower expression of CYP3A1 mRNA and CYP3A2mRNA Prompting that in terms of drug metabolism Kansui decoction party group is superior to Kansui powder party group. Compared with the whole party group, the whole party removed one or two anti-drug group has a relative reduce in CYP3A1 mRNA and CYP3 A2mRNA expression.Kidney:Compared with the model group Kansui decoction party group has lower expression of rat kidney AQP-2mRNA. The rest of the group compared with model group had no statistical difference (p> 0.05). Kansui decoction party group is better than the whole party removed one or two anti-drug in the inhibition of rat kidney AQP-2mRNA expression. And Kansui powder party group is lower than the whole party removed one or two anti-drug in the inhibition of rat kidney AQP-2mRNA expression. But the AQP-2 protein expression is not consistent with the result of genes, the Kansui powder party group can lower rat urine β-2MG,urine mALB and urine LDH. And in this aspect function is better than that of the whole party removed one or two anti-drug group. Compared with the whole party removed one or two anti-drug group Kansui decoction party group can lower rat urine mALB and urine LDH. Compared with the whole party removed one or two anti-drug group Kansui powder party group can higher rat urine EGF.Conclusion:(1)Compatibility and incompatibility of drugs under the different drug-delivery way:The whole party group of Kansuibanx ia soup has shown the result of a certain diuresis effects: ascitic fluid is reduced and the urine volume increased, ADH secretion decline as while. In which the Kansui decoction party group has a better function. Toxicity:Kansui decoction party group have certain protective effect on liver damage, but kidney toxicity is not obvious, two groups of drugs showed reduced to CK. whether needs further verification for the toxic effect. Immunomodulatory express:both two groups showed lower spleen index and IFN-y,TNF-a slightly increased at the same time, the VFGF showed a decrease trend, that two whole party groups have a certain increase in immune function. Liver P450 enzyme gene showed CYP2E1 expression, which prompt that delivery group has the possibility of promoting the trans formation of the carcinogenic factor. The gene expression of CYP3A1 and CYP3A2, prompt that drug metabolism has sped up the accumulation of toxic substances. This performance Kansui decoction party group is better than that of Kansui powder party group. Compared with the model group Kansui decoction party group has lower expression of rat kidney AQP-2mRNAwhich prompt that has a function of diuresis. Kidney mechanism aspects:GRF is decreased, urine β2-MG, urine mALB are increased and urinary EGF is reduced which prompt that early renal damage.CH2O negative hinted urine concentration as while, the above pathological changes may be associated with the formation of cancerous ascites, Two groups of drugs have some improvement. Kansui decoction party group is relatively well. In the whole party group under different drug-delivery way belongs to the "efficiency" compatibility.(2) Compatibility and incompatibility of add and subtract medicine:The whole party group can be seen a better advantage than the whole party group removed one or two anti-drugs at diuresis effects, immune regulation, improve the function of liver and kidney and the expression of P450 enzymes in the liver, kidney AQP-2. The whole party group removed one or two anti-drugs can be seen a better advantage than the whole party group In the aspect of improving hypokalemia. Toxicity assessment:the whole party removed Kansui group and the whole party removed Kansui and Kancao has a increasing at AST, ALP, TP content, reducing ALB and A/G ratio, weather is characterized by liver toxic effect remains to be further studied, and the whole party removed Kansui group has a MDA increased, which prompt that oxidative stress damage may exist. All parties in the assessment of ascitic fluid is increased and the urine volume reduced. The water to abdomen water euphorbia Kansui group increased and reduced the volume of urine. The whole party removed Kansui and gancao group blood Na+ content reduced, urine Na+is increased which prompt that tubular reabsorption dysfunction. Combined with renal mechanism, according to the results of the whole party removed Kansui and gancao group has a increase in urine mALb and uric LDH, with urine EGF reduced. That may further confirm the injury of renal, so the whole party removed Kansui and gancao may belongs to "weaker" compatibility.