| Ristolochic acid is a main category mixture of structurally related nitrophenanthrene carboxylic acids, and contained in some species belong to the Aristolochia genus, Aristolochic acids A is the major component. To follow therapeutic effect and adverse reaction of Aristolochic acids researches, the nephrotoxicity of some Chinese herbs that contain Aristolochic acids has been revealed. There are many Aristolochic acids, in which Aristolochic acid A is mostly related to the nephrotoxicity. The aim of this study was to investigate nephrotoxicity mechanism of Aristolochic acid A, through relationship between its metabolism information, changes in the level of energy substance and pathological changes of kideny in the living body.For the purpose of study, chuan fangchi are choosed as crude drug. Aristolochic acid A is extracted by 95% alcohol cool-immersing. The experimental rats are administrated with extract-water-solution. We established acute nephrotoxicity model and chronic nephrotoxicity model in our experiment. At the same time, the rats were sacrificed in given experimental session, and their kindey were collected.To detect Aristolochic acid A in rat kidney, we use the determination method for Aristolochic acid A in biological samples, which had been established in our laboratory. To detect ATP, ADP, AMP in rat kidney, we use the determination method for ATP, ADP, AMP in biological samples, which had been reported in the references. Comparison on study pathological changes between acute nephrotoxicity and chronicity nephrotoxicity of Aristolochic acid A in rats were performed by its metabolism information and changes in the level of energy substance.The results showed that there was no definite evidence that Aristolochic acid A can be accumlated in rat kideny, the amount of energy substance showed distinct downtrend in rat kideny during chronicity nephrotoxicity while the contents of ATP decrease to a significantly low level at acute nephrotoxicity. Through pathology observation, chronicity nephrotoxicity showed a series of chronic inflammation morphology changes, tissue fibrosis would take place at the last period; while acute nephrotoxicity showed that a plenty of tissue cells had taken place neorobiosis.In this study, we can initially concluded that kidney suffers aristolochic acid A at a certain usage narcotics dose and a certain usage narcotics period, which would lead to nephrotoxicity. Nephrotoxicity mechanism can be come true by an influence on ATP content. |
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