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OBJECTIVE： To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis， and to provide reference for clinical application and R&D of the decoction. METHODS： Based on TCM integrative pharmacology platform （TCMIP）， chemical component analysis of Xiaochaihu decoction， disease target prediction， gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of “TCM-chemical components-core targets-key pathways” was established， and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS： A total of 224 predicted chemical ingredients of Xiaochaihu decoction （including saikoside， ginsenoside， glycyrrhizin， etc.） interacted with 118 key targets about sepsis， including PF4， MYD88， TLR4， CD14， NOS3， etc. Its anti-sepsis mechanism involved nervous system， endocrine system， immune response and energy metabolism， etc. CONCLUSIONS： Based on “neuronal- endocrine-immune-metabolism”， Xiaochaihu decoction achieved its role in regulating sepsis by multi-level， multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis， and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action．
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Objective:To study the effect of IL-17 on viral myocarditis in mice. Methods:We randomly selected 20 wild type BALB/c mice as the control group,20 IL-17A-/- mice for IL-17A-/- group,20 IL-17A-/- mice for IL-17 group. Each mouse had intrap-eritoneal injection of Coxsackie virus B3 (Coxsackie virus B3,CVB3) to construct VMC model. The serum levels of IL-17 were detected by ELISA method,and Th17 cells were detected by flow cytometry. After 3 days of treatment with CVB3,100 μg IgG antibody was injected intraperitoneally in control group and L-17A-/- group,and 100 μg IL-17mAb was injected with IL-17 group. Mice myocardium was collected at 3rd,7th and 14th days,respectively,after CVB3 treatment. Pathological examination was carried out on the myocardial sections of mice and stained with H&E. Virus titer in mouse myocardium was examined. The contents of TNF-α,IL-6,IL-23 and IL-17 in myocardial tissue were detected by enzyme linked immunosorbent assay. Results:We successfully constructed the model of mice with viral myocarditis. The levels of Th17 and IL-17 in serum of IL-17 group were significantly lower than those in control group and IL-17-/-group. On the fourteenth day after CVB3 treatment,the degree of myocardial tissue damage in the control group was significantly higher than that in the IL-17A-/- group and the IL-17 group(P<0. 05),the degree of myocardial injury in IL-17 mice was higher than that in the IL-17A-/- group. The virus titer of the control group was higher than that of IL-17A-/-group and IL-17 group,and the control group was increased with the increase of CVB3 treatment phase (P< 0. 05). After the IL-17mAb was injected,the virus titer of IL-17 group was higher than that of IL-17A-/- group. The levels of IL-17, IL-23, IL-6 and TNF-α in IL-17-/- group and IL-17 group were significantly lower than those in control group. The levels of IL-17,IL-23,IL-6 and TNF-αin IL-17 group were significantly higher than those in IL-17-/-group (P<0. 05). Conclusion:IL-17 is an important inflammatory factor in viral myocarditis,and IL-17 deletion can protect myocardium from viral myocarditis in mice.
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Objective To investigate the expression of T cell immunoglobulin-and mucin-domaincontaining molecule-3 (Tim-3) in peripheral CD8 +T cells and its significance in patients with chronic hepatitis B (CHB).Methods Fifty-eight CHB patients and 16 healthy controls were enrolled.Tim-3 expression in CDs + T cells was detected by flow cytometry,and quantities of IFNγ-producing HBV-specific cytotoxic T lymphocytes (CTLs) in HLA-A2 positive subjects were detected by enzyme-linked immunosorbent spot (ELISPOT) test before and after the blockade of Tim-3/Tim-3L pathway.Paired t test was performed to compare the quantities of CTLs before and after the blockade,and nonparametric Spearman correlation analysis was performed to explore the correlation in quantitive data.Results Tim-3 expression in CHB patients was (14.2 ± 8.98 )％,which was higher than that of healthy controls (4.80 ± 2.92)％,and the difference was of statistical significance (x2 =92.48,P ＜ 0.05 ) Tim-3 expressions in 16 severe CHB patients and 42 mild CHB patients were ( 19.54 ± 10.95) ％ and (9.58 ± 7.30) ％,respectively,and the difference was statistically significant (x2 =77.24,P ＜ 0.05 ). Before the blockade of Tim-3/Tim-3L pathway,IFNγ-producing HBV-specific CTLs were 7.27 ± 3.14,and it increased to 19.62 ± 4.97 after the blockade ( t =2.95,P ＜ 0.05 ).Conclusion The upregulation of Tim-3 on peripheral CD8 + T cells may inhibit HBV-specific CTLs,and the blockade of Tim-3 pathway can enhance the proliferation of IFNγ-producing HBV-specific CTLs,thus can enhance antiviral effect.