| Purpose" Eighteen antagonisms " belongs to traditional Chinese medicine incompatibility, namely the combination will produce severe side effects or reduce damage and efficacy. However, the ancient physicians mixed views on this application. In recent years, researchers did a lot of scientific experiments on whether the " Eighteen antagonisms " is in contrast. However, more research is under physiological conditions to the anti-drug combinations themselves. But clinical use of drugs is in certain pathological conditions, and in compound with other drugs. Therefore, the "973" plan conducted the project based on the’Eighteen’the basic theory of traditional Chinese medicine incompatibility. Among them, the Six topics use gansuibanxia Decoction containing licorice and euphorbia anti-drug combinations as the carrier, selecting malignant ascites as a model, to investigate the " toxicity-efficacy " caused by the euphorbia and licorice anti-drug combinations according to the different conditions of compatibility. Early study has conduct on doses, proportions, varieties of processing, medicine way, times of administration.On the basis of preliminary results on the subject, we conducted further experimental study to research the effect of Gansuibanxia decoction that under different times of administration on biological effects in malignant ascites rats, and the change when decoction plus-minus Gansuigancao anti-drug combination, to further investigate whether the effect of euphorbia Decoction is related with the frequency of administration. Remove one or two anti-drug will increase or decrease efficacy or toxicity. Provide scientific support for the clinical application of euphorbia and licorice anti-drug combinations reasonably and safely. Provide scientific basis for wealth and improve the incompatibility theory of Eighteen antagonisms.MethodsOn the basis of preliminary results on the subject, we choose specific ratio (1:15), the specific dose (high dose), euphorbia and licorice specific processing varieties (vinegar euphorbia and licorice), euphorbia specific medicine mode (euphorbia into the bulk) of the euphorbia Decoction to do further experimental study. In this study, Wistar rats were randomly divided into blank group, model group, furosemide group, once or twice of Gansuibanxia decoction group, once or twice of Gansuibanxia decoction removed Zhigancao group, once or twice of Gansuibanxia decoction removed Cugansui group, once or twice of Gansuibanxia decoction removed Zhigancao and Cugansui group. Once group administration at morning, and twice group administration at morning and afternoon, which total dose is as much as the once group. Finally, based on the result of efficacy evaluation, expression of CYP450, expression of AQP-2, and Diuresis mechanismt, we discuss the "efficacy or toxicity" effect of Gansuibanxia decoction administrating once or twice daily on biological effects in malignant ascites rats, and make sure whether the "efficacy or toxicity" effect is related to anti-drug.Results1 Effect of Gansuibanxia decoction plus-minus Gansuigancao anti-drug combination that under different times of administration on Characterization of toxicity in malignant ascites rats(1) Heart From the result of CK and LDH, we can see that there was no significant difference between Gansuibanxia decoction plus-minus Gansuigancao anti-drug combination that under different times of administration and model group. From the cardiac pathology, there is no significant difference between the treatment group and the model group.(2) Liver The content of AST、ALT、GSH and AST/ALT ratio in once and twice of Gansuibanxia decoction group showed a decreasing trend, while the content of ALP、SOD showed an increasing trend, and the liver pathology results showed that the degree of liver damage mitigation. It showed that once and twice of Gansuibanxia decoction group have some improvement on liver damage walker-256 rats with ascites, and there is no liver toxicity. The improvement Enhanced a little on once group. When the Gansuibanxia decoction removed one or two anti-drug, the improvement reduced.(3) Kidney The content of BUN in blood in once and twice of Gansuibanxia decoction group showed an increasing trend.While the content of CRE in blood showed a decreasing trend. It showed that once and twice of Gansuibanxia decoction group have some improvement on kidney damage walker-256 rats with ascites, and there is no kidney toxicity. The improvement of once group is a little better than the twice one. When the Gansuibanxia decoction removed one or two anti-drug, the improvement reduced.2 Effect of Gansuibanxia decoction plus-minus Gansuigancao anti-drug combination that under different times of administration on efficacy evaluation in malignant ascites rats(1) Diuresis Effects It showed a certain diuresis effects on Euphorbia Decoction under different times of administration, and the effects of once group is a little better than the twice group. As the extension of time, abdominal circumference/body weight ratio decreased and weight increased with significant difference both in once and twice of Gansuibanxia decoction group; there is significant decrease between once of Gansuibanxia decoction group and the other once group on weight, but the increase is not significant in abdominal circumference/body weight ratio; There is significant decrease between twice of Gansuibanxia decoction group and the other twice group on weight, and the abdominal circumference/body weight ratio increased significantly. Diuresis effects is came by RASS, and has been confirmed in the urinary sodium ion content. When the Gansuibanxia decoction removed one or two anti-drug, RASS reduced, urine decreased, ascites increased, diuresis effects reduced. That is to say diuresis effects of the Gansuibanxia decoction is better than it removed one or two anti-drug.(2) Immunomodulatory Effects It showed a certain immunomodulatory effects on gansuibanxia Decoction under different times of administration. But the effect is not significant. And dosing frequency did not affect the function. When the Gansuibanxia decoction removed one or two anti-drug under different times of administration, immunomodulatory effects reduced.3 Diuresis mechanismt of Gansuibanxia decoction plus-minus Gansuigancao anti-drug combination that under different times of administration in malignant ascites rats(1) Liver Thus gansuibanxia Decoction can promote drug metabolism and reduce the accumulation of drug toxicity by increasing CYP3A1 and CYP3A2 gene expression. At the same time, it reduced CYP2E1 mRNA expression, to suppress ascites. When the Gansuibanxia decoction removed one or two anti-drug, CYP3A1 and CYP3A2 gene expression reduced, CYP2E1 increased, inhibition of ascites effects reduced. That is to say, diuresis effects reduced.(2) Kidney Both the once and twice of Gansuibanxia decoction group can reduce the AQP-2 mRNA expression, and the effect roughly equivalent. When the Gansuibanxia decoction removed one or two anti-drug, the effect reduced. That is to say, Euphorbia Decoction performed well on diuresis effect.Conclusions1 Suitable and contraindicated conditions under different times of administrationBoth once and twice of Gansuibanxia decoction groups show a certain effect on diuresis effect, improvement of liver and kidney. Once group performed a litter better than the twice group on diuresis effect, improvement of liver and kidney, the effect of promoting drug metabolism, reducing the accumulation of drug toxicity. While the performance equal on the metabolism of inhibition of ascites. Once and twice administration of euphorbia and licorice anti-drug combinations in the compound compatibility condition are suitable for application. Once group was superior to the twice group.2 Suitable and contraindicated conditions under different times of administration removing one or two anti-drugBoth once and twice of Gansuibanxia decoction removing one or two anti-drugs groups show a certain effect on diuresis effect and regulation of AQP-2 mRNA. But these effects are worse than Gansuibanxia decoctions. There showed no toxicity on heart, liver and kidney. |
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