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The Study on Animal Model of Schizophrenia Roled by Nanoparticles NF-κB Decoy Gene

Author: LvLuXian
Tutor: ZhangYangDe
School: Central South University
Course: Biomedical Engineering
Keywords: nanometer polybutylcyanoaciylate schizophrenia NF-κB animal models
CLC: R749.3
Type: PhD thesis
Year: 2006
Downloads: 161
Quote: 0
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Abstract


Objective:1. To prepare the gene carrier of nanometer practical in order to explore the preponderance in binding and protecting DNA and in playing a release and targeting role.2. To explore the immunizing changes induced by NF-κB in schizophrenia animal models.3. To investigate the intervence effects on mediated by NF-κB after NF-kB decoy gene was used on schizophrenia animal models.Methods:1. one way experiment and orthogonal experiment were used to analyze and optimize the condition of making Mean diameter nanoparticles(NPs) fitted to be NPs genetic carrier by using emulsion polymerization method and changing its surface character.2. NPs NF-κB decoy gene was made by connecting NPs acted as genetic carrier and dumb bell NF-κB nanometer decoy gene.3. Animal model of Schizophrenia was found in male wistar rats whose weight were 350±20g by being injected different dosage, 0.3mg/kg、0.6mg/kg、1.2mg/kg、1.8mg/kg、2.4mg/kg MK-801, and the effects of MK-801 were observed in behavior to optimize the optimal dose of model building.4. NPs NF-κB decoy gene was used to be injected in lateral cerebral ventricle to investigate the change of animal behavior and the effects on the mRNA expression of TNF-α、IL-1β、IL-2、IL-6、IL-10.The data was deal with by SPSS statistical package.Results:1. The conditions to prepare average size 74±3nm NPs by using one way experiment and orthogonal experiment, pH of the reaction solution is 2.5,BCA monomer density’is 1%,Mix round velocity is 1000r/min, superficial activator is 1% Dextran70, 0.3% Tween-80 is mixed in this system, reacted in 25C for three hours and adjust pH to keep 6-7,then mix them round for one hour. All NPs are uniformity sphericity , superficial smoothness and integrity ,size distributing is normal distribution and well-distributed, span just is about 0.21 and decentralization is well.2. To adopt 0.25% CTAB to change the quality blank PBCA-NP, elevate Zeta potential from -23. 0mV to +23mV. Cell toxicity was mensured by using MTT. No cell toxicity in PBCA-NP and CTAB-PBCA-NP<100ng/μl.3. NPs are changed in superficial quality can combine with dumb-bell NF-κB decoy gene. Carry drug dosage is 96%, and superficial form and average size has not changed after combining. The ability to resist DNase I and blood serum degenerating has improved remarkablely, the same as the ability to inhibit supersound destructing improved.4. According to the result of dose-response measurements of serial MK-801 dosages in the male wistar rats , 0.6 mg/kg and 100μl/20g MK-801 was determined as the optimum dosage that can induce the typical schizophrenia symptoms, including obvious hyperlocomotion, stereotype ataxia and apathy to social behaviour. At the same time the wistar rats still keep active ability and no toxicosis symptoms.5. NPs NF-κB decoy gene can inhibit the activity of NF-κB in upper efficiency in animal experiment .which compared with naked decoy DNA is different significantly(P=0,0324). Nanoparticles NF-κB decoy gene can inhibit well the activity of NF-κB in MK-801 model rats.6. After NPs NF-κB decoy gene roles model rats, action of rats generates significantly change---symtoms induced by MK-801 such as hyperlocomotion, stereotypy and ataxia action compared to control group. The effect on motor behavior decrease by 45 percent, which reach extremely significant level (P=0.007);the effect on stereotypy also reach significant level (P=0.046) . The improvement of ataxic is reaching significant level(P=0.026) too.7. After NPs NF-κB decoy gene roles model rats induced by MK-801, changes take place in the mRNA expression levels of NF-κB, TNF-α, IL-1β, IL-2, IL-10. Expression up-regulated in NF-kB, IL-10, but down-regulated in TNF-α,IL-1β,IL-2. Significant difference exist between before and after treatment with NPs NF-κB decoy gene.Conclusion:1. Little and well-distributed PBCA nanoparticles was prepared successfully. Modified by cationic surfactant CTAB, this nanoparticles can be used as optimal NPs genetic carrier. NPs carried NF-κB decoy gene can inhibit the activity of NF-κB.2. Schizophrenia models induced by MK-801 were established,it can be found that the expression of mRNA of multiple cell factors were abnormal and NF-κB function was hyperfunction in schizophrenia models.3. The first time to investigate the pathology of schizophrenia by nanoparticles (NPs) genetic carrier. The conclusions are as follows: NPs genetic carrier made with NF-κB decoy DNA can inhibit activity of NF-κB, which can be founded reliable platform to study the relationship between schizophrenia and immunization.4. The partly symptoms of model animals of schizophrenia can be reversed when the experimental animals were performed by NPs genetic carrier made with NF-κB decoy DNA. It confirmed that the relationship between NF-κB and social behavior the models of schizophrenia were existed.

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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Schizophrenia
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