| Objective: In this study we choosed medicinal namoparticles asa carieer in order to make A、B、C、D into medicinal namoparticles A’、B’、C’、D’ to explore the effect and mechanism of drug-resistant ofMycobacterium tuberculosis. Methods:(1) A、B、C、D were encasedin medicinal nanoparticles to make them to be medicinal nanoparticlesA’、B’、C’、D’ with the help of four constant temperature magnetic stirrer;(2) To identify tuberculosis mycobacterium type we used Acid roche drugsensitive medium and gene chip technology, then we selected sensitivestrain H37Rv and three resistant strains (respectively, resistant toisoniazid, rifampicin and multi-drug resistant strains) as experimentobject;(3) The experiment was made up of experimental group and thecontrol group, experimental group1: Medicinal nanoparticles A、B、C、D; experimental group2: A、B、C、D; experimental group3: experimentalgroup1and experimental group2respectively combined with INH;experimental group4: experimental Group1and experimental group2respectively in joint RFP. The experimental group1, group2and group3and group4, respectively affected the four kinds of TB strains.Thecontrol group was composed of positive control group、 negative controlgroup and blank control group. Positive control group:INH and RFP respectively affected the four kinds of TB strains. Negative controlgroup： Four strains of mycobacterium tuberculosis bacterium fluidgroup.Blank control group: Mie7H9culture solution.(4)Firstly,medicinal namoparticles A、B、C、D as well as A’、B’、C’、D’ respectively affected on the four kinds of TB strains.Then, themedicinal namoparticles A’、B’、C’、D’ as well as A、B、C、D respectivelycombined with INH or RFP to affect on the four kinds of TB strains.Finally,with the help of MTT method we investigated the effect of eachkind of strain.（5）By gene chip technology we detected the role ofMedicinal nanoparticles C to drug-resistant strains and themycobacterium tuberculosis resistant loci fluorescence values before andafter the change. Results:(1) Neither medicinal namoparticles A、B、C、D nor A’、B’、C’、D’ had inhibitory effect on each kind of strain. INH hadno inhibitory effect on Isoniazid-resistance strain and RFP had noinhibitory effect on rifampicin-resistant strain.Neither of INH nor RPFhad inhibitory effect on multidrug-resistant strains, but,both of them weresensitive to H37Rv strain.(3) Medicinal namoparticles A’、B’、C’、D’ aswell as A、B、C、D respectively combined with INH or RFP had inhibitoryeffect on four kinds of strains. Simultaneously, experimental resultsshowed that the drug resistant strains of inhibition increased with theincrease of drug dose in addition showed a trend of increasing. Also, thedegree of dependence of the drug-resistant strains depended on the drug dose.(4) Compared with the positive control group, the resistance indexof drug-resistant strains from experimental group3and group4weresignificantly decreased (p <0.05). The resistance index of medicinalnanoparticles A’、B’、C’、D’ combined with isoniazid or rifampin felledmore obviously than the resistance index of A、B、C、D combined withisoniazid or rifampin.And The resistance index of different drug-resistantstrains decreased in different degree.(5) After the role of medicinalnanoparticlesC,the drug-resistant sites of drug-resistant strains wereunchanged, but the resistance loci gene expression descended comparedwith the drug used before. Among them,the expression of katG gene fromisoniazid-resistance strains dropped in47.5%.And the rifampicin-resistantstrains of the rpoB gene expression decreased by97.3%.Themultidrug-resistant mutant katG gene expression decreased by14.7%,rpoB gene expression decreased by60.1%.Conclusion:(1) Neithermedicinal nanoparticles A’、B’、C’、D’ nor A、B、C、D had inhibitoryeffect on drug-resistant TB strains.(2) Medicinal namoparticles A’、B’、C’、D’ as well as A、B、C、D respectively combined with isoniazid orrifampicin had inhibitory effect on drug-resistant Mycobacteriumtuberculosis.And this inhibitory effect was positively correlated with thedose,and the effect of the former was stronger.(3) Medicinalnanoparticles of A’、B’、C’、D’ as well as A、B、C、D probably by theway of cutting the expression of drug resistance gene in drug-resistant mycobacterium tuberculosis,so that can reduced the resistance and playeda role of reverse.(4) Medicinal nanoparticles A’、B’、C’、D’ combinedwith classic anti-TB drugs such as isoniazid and rifampicin is expected tobecome the effective method to treat drug-resistant TB. |
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