| ObjectiveIn the present paper, the influence of Bushen Jianpi Jiedu Prescription on serum HBV DNA and HBsAg and HBeAg quantitative and hepatic function indexes in the chronic HBV carriers was studied. By observing the impacts of Bushen Jianpi Jiedu Prescription on the CD4+CD25+Treg expression frequency and functions, DC mature deficit and quantity and immune function, and the cellular immune functions, in the chronic HBV carriers, the mechanisms of the prescription in inhibiting immune resistance and enhancing the cellular immune function were explored, which could bring the effective Chinese herbal compound for the chronic HBV carriers and provide the study strategies and theoretical basis for the traditional Chinese medicine treatment of chronic HBV carriers.MethodsWith the placebo-controlled method, the cases were divided into two groups. In the treatment group,30cases of chronic HBV carriers were applied with Bushen Jianpi Jiedu Prescription. In the control group,10cases of healthy volunteers were applied with placebo, and after48weeks the therapeutic effects were assessed, and the following indexes were observed.(1) changes of the serum HBV DNA and the HBsAg and HbeAg quantitative and the negative transforming situation;(2) Influence of CD4+CD25+Treg expression frequency and functions (IL-10and TGF-β);(3) Impacts on DC mature deficit (morphology and surface marker analyses), quantity and the immune function indexes (MLR, IL-12and IFN-γ);(4) Impacts on cellular immune function indexes (CD4+T cells, CD8+T cells and CD4+/CD8+) and the occurrence of adverse effects. Results1. Clinical therapeutic effects of Bushen Jianpi Jiedu Prescription in treatment of chronic HBV carriersAfter48weeks following treatments, in the treatment group, the serum HBV DNA level decreased from8.2701g IU/ml to7.168lg IU/ml, with the average decreasing as1.102lg IU/ml, with significant difference (P<0.05); Compared with the baseline level, the case number of the decreasing level higher than11g IU/ml,2lg IU/ml and3lg IU/ml were14(50.00%),6(17.86%) and2(7.14%), and no case of negative transforming. After the treatments, the case number of the serum HBV DNA level lower than105IU/ml was3(10.71%). In the three cases, before treatments, the serum HBV DNA levels were8.25X106IU/ml,2.93×107IU/ml and6.74×105IU/ml, and after treatments, they were2.69×103IU/ml,5.41×103IU/ml and1.82×104IU/ml, respectively, with the decreasing as3.487lg IU/ml,3.734lg IU/ml and1.569lg IU/ml.After48weeks following treatments, in the treatment group, the serum HBsAg quantitative level decreased from4.618lg IU/ml to3.993lg IU/ml, with the average decreasing as0.625lg IU/ml, with significant difference (P<0.05); Compared with the baseline level, the case number of the decreasing level higher than0.5lg IU/ml,1lg IU/ml and2lg IU/ml were9(32.14%),5(17.86%) and1(3.57%), and no case of negative transforming. After the treatments, the serum HBeAg average level decreased from the baseline1108.52S/Co to774.07S/Co, with the average decreasing as334.45S/Co, with significant difference (P<0.05). There was no case of serum HBeAg negative transforming.After48weeks following treatments, in the treatment group, the serum ALT, AST and GGT levels decreased from33.8IU/L,26.3IU/L and31.7IU/L to27.4IU/L,18.7IU/L and25.1IU/L, respectively.2. Mechanisms of Bushen Jianpi Jiedu Prescription on immune regulation in chronic HBV carriersThe peripheral serum CD4+CD25+Treg expression frequency was7.68%in the chronic HBV carriers with immune resistance, which was obviously higher than that of5.72%in the healthy volunteers (P<0.05), and the contents of serum IL-10and TGF-β were apparently higher than those in the healthy people(P<0.05). After48weeks following intervention, the peripheral serum CD4+CD25+Treg expression frequency and the serum IL-10and TGF-β contents were obviously decreased (P<0.05), which were approximated to those in the healthy volunteers (P>0.05, respectively).The expression levels of DC mature surface markers such as HLA-DR, CD86, CD80and CD1a in the chronic HBV carriers with immune resistance were61.34%,55.78%,42.63%and43.17%, respectively, which plus DC induced MLR ability and the IL-12and IFN-γ expressions in MLR serum were obviously lower than those in the healthy people (P<0.05, respectively). After48weeks following Bushen Jianpi Jiedu Prescription intervention, the IL-12and IFN-γ expressions in the MLR serum were apparently increased, and the DC induced MLR ability was obviously enhanced (P<0.05, respectively). However, after48weeks with intervention, the HLA-DR, CD86, CD80and CD1a expressions and the IFN-γ expressions in the MLR serum in the treatment group were still obviously lower than those in the control group (P<0.05, respectively), while the IL-12expressions were approximated to those in the healthy volunteers(P>0.05).For the cellular immune function indexes, the peripheral serum CD3+and CD4+T cell expressions in the chronic HBV carriers were62.94%and32.68%, which were lower than those of72.28%and39.49%in the control group, respectively. The expression of CD8+T cells was29.03%, which was obviously higher than that of23.04%in the control group. The CD4+/CD8+ratio in the chronic HBV carriers was1.18, which was lower than that of1.77in the control group (P<0.05, respectively). After48weeks following Bushen Jianpi Jiedu Prescription intervention, the CD3+and CD4+T cell expressions in the treatment group increased to67.35%and37.22%, respectively, but the CD8+T cell expression decreased to24.41%, and the CD4+/CD8+ratio obviously increased to1.61(P<0.05, respectively). After48weeks, compared with those in the control group, the CD3+cell expressions were still lower than those in the control group (P<0.05), but there were no significant differences of the CD4+T and CD8+T cell expression and the CD4+/CD8+ratio between the two groups (P>0.05, respectively).ConelusionsFor the chronic HBV carriers, Bushen Jianpi Jiedu Prescription could inhibit the HBV DNA duplication and the expressions of serum HBV markers such as HBsAg and HBeAg, which could protect the liver and reduce the risks of disease progress brought by immune resistance.For the chronic HBV carriers, Bushen Jianpi Jiedu Prescription performs the anti-HBV actions via down-regulating CD4+CD25+Treg expression, promoting DC mature, enhancing cellular immune function and inhibiting/eliminating HBV, namely:(1) Reduces the stimulation to CD4+CD25+Treg via decreasing the serum IL-10and TGF-β secretions, down-regulates the CD4+CD25+Treg expression, alleviates the immune inhibition induced by CD4+CD25+Treg, provokes the HBV specific immune response hence inhibits/eliminates HBV.(2) Enhances the DC antigen submission via promoting DC mature and enhancing DC induced MLR ability, regulates Thl/Th2immune response, induces T cell effective immune response hence inhibits/eliminates HBV.(3) The DC mature induces the iDC secretion of CD4+CD25+Treg expression reduced. The decreasing of Treg expression promotes the integration of DC and non-regulative T cells and inhibits DC activation and mature and stimulates the T cell proliferation, which consequently increases the expressions of CD3+and CD4+T cells, decreases the expression of CD8+T cells, regulates the CD4+/CD8+ratio normal and induces the virus specific CTL ability hence inhibits/eliminates HBV. |
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