| AIDS (acquired immunodeficiency syndrome, AIDS) is a systemic immune by HIV (human immunodeficiency virus, HIV) serious damage of infectious diseases, Because the population of HIV/AIDS has certain particularity, occult, health protection consciousness, as well as the public social discrimination of HIV/AIDS and to avoid further increased the difficulty of prevention and control, lead to rising number of HIV/AIDS. Intravenous drug infections become the main way of the spread of AIDS in Yunnan Province, therefore, in the drug group, is to detect the HIV antibody positive rate has been high.Methamphetamine belongs to amphetamines stimulants, as well as is called deoxygenate ephedrine, commonly known as "crystal meth". It has the drug dependence (mainly psychological dependence), central nervous excitement, hallucinogenic, appetite suppression and sympathetic effects and other pharmacological and toxicological characteristics. It is the one of control active substances by United Nations convention on psychotropic substances. In recent years methamphetamine abuse is more common, it will be the high risk on HIV infected and transmitted.Autophagy is a process of lysosome dependent on pathway for degradation of cytoplasmic proteins and organelles, conserved highly on the evolution, widely existed in yeast, worms, fruit flies and senior vertebrate cells. Autophagy plays very critical roles in the growth and development, cell differentiation and organism response to environmental stress. In the process of intracellular bacterial infection and virus infection the host cell, on another hand, autophagy can promote the remove of pathogens of the infected cells, on the other hand, infected pathogenesis escape from autophagy through some mechanisms, which is involved in the pathogenesis of infection of germ and virus. In the progress, LC3(microtubule-associated protein1light chain3, as well as autophagy related protein8, Atg8, in mammalian) Continues to be recruited to the autophagy precursor, the precursor for extending autophagy plays a key role in the regulation. As same time, p62(sequestosome-1) has an important role in regulating discrimination and degradation of substrate.Major histocompatibility complex (MHC) is formed by a group of genes closely chain group, located in a particular area of the chromosome in animals or people, are highly polymorphic. Its coding molecules express in different cell surface, participate in antigen presentation, restricting the mutual recognition between cells and inducing immune response. MHC is divided into three categories, MHCII locates on the antigen presenting cells (APC). is used to provide foreign antigens to the T helper cells, to start the immune response.Thioredoxin (Trx) is a widely expressed in various kinds of biological tissues and cells, low molecule weight protein, plays an important role in regulating the redox reaction. At the same time, it also has the biological functions such as transcription regulation, resistance to apoptosis, It has close relationship with tumor, rheumatoid arthritis and cardiovascular disease, such as a variety of human diseases has important research value. Thioredoxin has many family members, thioredoxin-1(Trx-1) has been studied well.Methamphetamine (METH) is used to stimulate acute T lymphocyte leukemia cell line (Acute T cell leukemia cell line. Jurkat) to build drug abuse cell model, to study the mechanism on interaction between Trx-1and cell autophagy, to explore the mechanism on MHCII expression during immune response to drug abuse, further demonstrate the mechanism on defected immunity after abuse, to provide new-theoretical basis with improving immunity of abusers, also provide new issue for the prevention of AIDS.The main results were as follows:Methamphetamine (METH) dose dependent reduces the Jurkat cell vitality. Aafter the short, long time METH stimulating Jurkat cells, to detect the Trx-1, LC3II, P62changes*results showed that METH not only can reduce of the Trx expression, and LC3II increased in time dependent manner, P62are decreased on the opposite. This suggests that METH induces autophagy in Jurkat cell, and the expression of autophagy is related to the Trx-1expression. After METH stmulating control mice and the overexpression transgenic mice of hTrx-1, the expressions of Trx-1, LC3II, MHCII were examined. The results show that changes of Trx-1and LC3II are similar with cell level, suggesting METH also induce autophagy in mice. Results show that Trx-1expression in transgenicmice is not decreased, non-gm group, verified the cell autophagy occurs in the process of addiction. While LC3II and MHCII expressions in transgenic mice are reversed compared with control group. This suggests that overexpression of Trx-1can enhance expressions of LC3II and MHCII. Thus, overexpression of MHCII may improve immunity of drug abusers.Conclusion:Trx-1plays an important role in regulating the expressions of autophagy and MHCII by METH. Trx-1may be a therapeutic target for treating immunity defects by METH. |
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