Effect of Aidi Injection on Expression of Cytochrome P450 Enzyme in DEN-induced Hepatocellular Carcinoma Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To study the effect of Aidi injection （AD） on the expression of cytochrome P450 isoenzyme 1A2，2E1，3A2，2C11（CYP1A2，2E1，3A2，2C11）mRNA and protein in rats with N-nitrosodiethylamine （DEN） chemically induced primary hepatocellular carcinoma（HCC）. Method:Three healthy SD male rats were randomly selected as the blank group， and the remaining rats were treated with DEN intermittently induced primary hepatocellular carcinoma rat model. After success of the model， the rats were randomly divided into model group and AD group， with 3 rats in each group. The rats in the blank group and model group were intraperitoneally injected with 10 mL·kg^-1 saline， while those in the AD group were intraperitoneally injected with 10 mL·kg^-1AD once a day， a total of 14 d intervention. Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of CYP1A2， CYP2E1， CYP3A2 and CYP2C11， respectively. Result:Real-time PCR results showed that after 14 days of drug administration， compared with the blank group， the mRNA expressions of CYP1A2， CYP2E1， CYP3A2 and CYP2C11 were all down-regulated in para-cancerous tissue （PCT） and cancerous tissue （CT） in model group， and there were significant differences （<italic>P</italic><0.05，<italic>P<</italic>0.01）. Compared with the model group， the mRNA expressions of the four subtype enzyme were significantly down-regulated in PCT in the AD group（<italic>P</italic><0.05，<italic>P<</italic>0.01）， while the mRNA expressions of the four subtype enzyme were significantly up-regulated in CT （<italic>P</italic><0.05）， and the expression was down-regulated overall. Western blot results showed that compared with the blank group， the protein expressions of CYP1A2， CYP2E1， CYP3A2 and CYP2C11 in CT of the model group were significantly down-regulated （<italic>P</italic><0.01）， and the protein expressions of CYP3A2 and CYP2C11 were significantly down-regulated in PCT （<italic>P</italic><0.01）. Compared with the model group， the protein expressions of CYP1A2， CYP2E1， CYP3A2 and CYP2C11 in CT and PCT were down-regulated in the AD group， but the differences were not statistically significant. Conclusion:AD can down-regulate the mRNA and protein expressions of CYP1A2， CYP2E1， CYP3A2 and CYP2C11 in rat liver tissues. In clinical use of AD， attention should be paid to drug interactions that may be caused by CYP450 enzyme inhibition.