An Experimental Study Of Matrine Combined With Albendazole On The Secondary Echinococcus Multilocularis In Mice

Objective: To evaluate the effect of matrine(Mat) on experimental secondary Echinococcus multilocularis in mice and synergistic effect of co-administration with albendazole(ABZ ),and to explore immune status and the outcome of murine Alveolar Echinococcosis(AE), as well as the change and the metabolic reaction of hepatic enzyme after pharmic treatment with matrine (Mat) and albendazole (ABZ).Methods: Mice infected with Echinococcus multilocularis were divided into four groups randomly,including Matrine alone,Albendanzole alone,combination of the two drugs above and control. At the same time selecting healthy mice as blank. After being treated 60 days ,the mice were dissected. The major judging criteria including cyst wet weight,thymus index,spleen index, inhibition rate, and histopathological changes of cyst both microscopically and electron microscopically. In addition ,the levels of IL-2, IL-4,IL-6 and TNF-a in serum were detected by radioimmunoassay (RIA)before and after therapy. NO, LD content and LDH, NOS, iNOS, Na⁺-K⁺ATPase, Ca²⁺-Mg²⁺ATPase activity in hepatic tissue homogenate from AE animal model treated by drugs were measured by chromatometry.Results: Matrine alone or combination with Albendazole had obviously effect against growing of E.multilocularis cyst (Inhibition rates were 77.61% and 89.88% respectively).There was significant difference in the cyst wet weight between therapeutical groups and control as shown by the results in mice (P＜0.01); The thymus index in the blank group was lower than that in the Echinococcus multilocularis infection groups,but the spleen index in the blank group was higher than that in the Echinococcus multilocularis infection groups (P＜0.05). Such cytokines as IL-4,IL-6 and TNF-a decreased after treatment(P＜0.05), and the levels of IL-4 and TNF-a decreased remarkably in the co-administration group (P＜0.05). Cytokine IL-2 in the co-administration increased after treatment(P＜0.05), compared with the blank group (P＞0.05). The content of NO and the activity of NOS and iNOS in the hepatic tissue decreased after treatment (P＜0.05).Especially the activity of iNOS in the Mat and co-group showed a much more decrease than that in ABZ group (P＜0.05).The LDH activity also decreased after treatment (P＜0.05), However, only in the co-administration group, did the LD content decrease(P＜0.05). The activity of Na⁺-K⁺ATPase, Ca²⁺-Mg²⁺ATPase in the hepatic tissue increased after treatment (P＜0.05), The increase of Ca²⁺-Mg²⁺ATPase in both the Mat group and the co-administration group was significantly different from the ABZ group (P＜0.05).Conclusion: Matrine had obvious inhibitory effec against E.multilocularis. The combination of the Matrine with Albendazole had stronger inhibition action, After treatment,cytokines IL-4,IL-6,TNF-a depressed and cytokine IL-2 increased. The hepatic functions of the mouse infected with E.m had improved significantly after treatment,therefore Matrine could heighten the immunity of the mice and improve the hepatic injury caused by AE. Matrine has marked inhibitory effects on E.m growth in vitro and in vivo, which is probably related to intervention of calcium ion passages and reversion of the multi-drug resistance.