Intervention Effect Of The Invigorating Spleen And Kidney And Detoxifying Principle On Simian Immunodeficiency Virus-infected Chinese Rhesus Macaques And Exploring The Progressive Factors Of Different Animal Model

ObjectiveThis research aims to evaluate the intervention effect of the invigorating spleen and kidney and detoxifying principle on simian immuno deficiency virus-infected Chinese rhesus macaques and search after the progessive factors of different model and explore Pathological mechanism of long term non-progressive animal model.MethodsFirst chapter:evaluating the intervention effect of the invigorating spleen and kidney and detoxifying principle on simian immunodeficiency virus-infected Chinese rhesus macaquesDiving 8 AIDS rhesus monkeys, which were infected at the same period and had a equal baseline, into two groups randomly. Both groups received 8-weeks consecutive treatment of herb and anti-virus agents. Blood sample and inguinal superficical lymph nodes are collected regulary. The gastrointestinal mucosa is collected after the experiment is finished. Following tests were carried out:detecting immune index and virology index as follows:T cell pure subgroup, memory subgroup, function subgroup, intestinal lymphatic homing receptors, plasma viral loading and tissues containing SIVRNA and SIVDNA. The TCM symptom and pathological structure are also used in these tests. Finally, the difference in indexes in the treatment of Chinese herb and anti-viral drug group were compared and analysed.Second chapter:search after the progessive factors of different modelSelect the LTNP, NP, RP characteristics of monkey,10 each group, with the same period 5 healthy monkeys in comparison, difference analysis and comparison among different types of T cell subsets, TCM(Traditional Chinese medicine) syndrome index and pathology of lymph node, find the influence factors of different types of progress, and established the discriminant equation to predict the risk.Thirdchapter:Explore the intrinsic pathological mechanisms about the long-term non-progressive SIV macaque modelElected 4 the long-term non-progressive HIV rhesus. Gave three normal monkey (Normal) and four general progressive (NP) SIV monkey which entered the trial in the same period as control. Continuous observation of six months, during the three groups were observed without any intervention. Regular blood, collected superficial inguinal lymph nodes and collected gastroin testinal mucosa specimen at the end of experiment. Detected T cell subsets innocence, memory subsets, functional subsets, intestinal lymphoid homing receptor and other immune index;plasma viral load and tissues virology indicators, such as SIVRNA and SIVDNA;traditional Chineses syndrome indicators and pathological structures detect. Then analyzed the difference index of each three groups.ResultsFirst chapter:evaluating the intervention effect of the invigorating spleen and kidney and detoxifying principle on simian immunodeficiency virus-infected Chinese rhesus macaquesTraditional Chinese medicine of invigorating spleen and kidney and detoxifying principle although not like HAART significantly decreased plasma and intracellular SIV DNA/RNA, but can increase the peripheral blood CD4. The subsets of CD4 cells is naive CD4 cells, at the same time, the down-regulation of CCR5, up regulate the expression of CD28 beta 7+ and CCR9 increased significantly. Beta 7+ expression and CCR9 in gastrointestinal mucosa was significantly lower. This change, there may be some correlation with decreased MAVS protein. In addition to delaying the emergence and development of the spleen deficiency to a certain extent, compared with the HAART group, lymph node pathology showed preserved more complete, displaying Chinese medicine has considerable clinical value.Second chapter:search after the progessive factors of different model1 Plasma viral load are in the peak reached in 10-14 days after infection in each group, differentiation appeared on the platform period.2 Compared with Normal, WBC of RP type was significantly higher, CD4 and LYM ratio was significantly lower; while LYM number of LTNP type was higher; 3 Compared with other types, RP type beta 2-MG was significantly increased, T3 decreased.4 RP type lymph nodes decreased in the platform, degeneration of germinal center was significantly reduced, significantly different from the other types.5 WBC and LYM ratio into the discriminant equation before infection, T4 and Log10RNA of set point into the discriminant equation in platform period. To test the established discriminant function of the uniform rate, theory to distinguish the total consistent with the actual data rate respectively is 57.1% and 91.2% before infection and platform period.Thirdchapter:Explore the intrinsic pathological mechanisms about the long-term non-progressive SIV macaque modelPlasma viral load in group LTNP, CD4 and the ratio, the number of memory subsets, functional subsets were in line with our expectations, mostly between NP group and normal group, we found that LTNP group lymph nodes in the low expression of CCR5 in the intestinal mucosa, chemotactic factor effector T cells, and higher closer to the normal group. This may be an important characteristic of LTNP, and even participate in the formation of LTNP. As the virus receptor TLR, RLR family protein MAVS connector signal in LTNP was significantly lower than that in NP group, the LTNP in lymph node inflammatory cell factor is low, thereby reducing the cell activation, Further delay the disease process of LTNP infection, the monkey is very low in natural SIV viral load. The index shows that the LTNP is in a relatively stable state, but not excessive activation state in SIV infection.Conclusion1 The recipe can increase CD4 naive cells, at the same time, the down-regulation of CCR5, up regulate the expression of CD28, beta 7+and CCR9 increased significantly, and the pathology of the lymph node structure preserved more complete, has a certain clinical value and application prospect.2 There are obvious differences in the platform among three kinds of SIV Rhesus model, the RP type has more obvious deficiency syndromes of spleen and kidney, suggesting that deficiency syndromes of spleen and kidney may be a key factor in the rapid progressor of AIDS. The WBC and LYM ratio before infection can be used as a reference for evaluation of different types of progress, and platform phase of LoglORNA and T4 can be used in different types of progress risk prediction.3 LTNP index between Normal and NP, and even closer to the normal group. The low expression of CCR5 in lymph nodes, chemotactic factor in intestinal mucosal effector T cells, and more closer to the normal group, as the virus nucleic acid receptor TLR, RLR family protein MAVS connector signal in LTNP was significantly lower, may make the LTNP lymph node inflammation cytokines be low, reducing lymphocyte activation and disease progression. These are likely to be involved in the formation of LTNP, resulting in low SIV in natural infection in monkeys.