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Outline
To investigate the mechanism of Jiawei Guipi Decoction (加味归脾合剂) in regulating the Janus inases 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3) signaling pathway to improve T helper cell 17 (Th17) /regulatory T cells (Treg) immune balance in primary immune thrombocytopenia (ITP) mice.
Sixty female BALB/c mice were randomly assigned to six groups: normal group, model group, Jiawei Guipi Decoction low, medium and high dose groups, and prednisone group, with 10 mice in each group. Except for the normal group, the other five groups were administered intraperitoneal injection of MWReg30 antibody to establish the ITP model. After successful modeling, the corresponding treatments were administered. The blank control and model groups were given an equivalent volume of sterile drinking water by gavage, while the Jiawei Guipi Decoction low, medium and high dose groups received the administration with the corresponding doses［13.49, 26.99, 53.97 g/ (kg·d), respectively］. The prednisone group was administered prednisone 9.25 g/ (kg·d). The treatments lasted for 14 consecutive days, and after this period, the samples were collected. The effects of Jiawei Guipi Decoction on platelet count, splenic pathology, the number of Th17 and Treg cells in peripheral blood and spleen, the expression levels of interleukin (IL) -17, IL-21, IL-22, IL-10 in peripheral blood, and the protein expressions of p-JAK2, p-STAT3, retinoic acid receptor-related orphan receptor γt (RORγt) and forkhead transcription factor p3 (Foxp3) in the spleen were evaluated.
Compared with those in the normal group, the mice in the model group exhibited a significant decrease in peripheral blood platelet count, marked histopathological alterations in splenic tissue, a reduced number of Treg cells and an increased number of Th17 cells in both peripheral blood and spleen. Furthermore, the expression levels of splenic p-JAK2, p-STAT3 and RORγt protein were significantly up-regulated, accompanied by elevated concentrations of IL-17, IL-21 and IL-22, and a decreased level of IL-10 in peripheral blood (P<0.01) . Compared with the model group, all treatment groups significantly increased the peripheral blood platelet count, improved the pathological status of the spleen, markedly reduced the number of Th17 cells, and elevated the number of Treg cells in both peripheral blood and spleen, substantially decreased the levels of IL-17, IL-21 and IL-22 in peripheral blood and increased the level of IL-10 (P<0.05, P<0.01) . Among the treatment groups, the high-dose group showed superior efficacy compared to the low-dose, medium-dose as well as the prednisone groups (P<0.05) . Moreover, Jiawei Guipi Decoction significantly down-regulated the protein expression levels of splenic p-JAK2, p-STAT3 and RORγt (P<0.05, P<0.01), while up-regulated the protein expression of Foxp3 (P<0.05, P<0.01). The high dose group exhibited a more pronounced reduction in the protein expressions of p-JAK2, p-STAT3 and RORγt compared with the low dose group (P<0.05) .
Jiawei Guipi Decoction exhibits significant therapeutic effects in ITP mice. The mechanism may involve the inhibition of the JAK2/STAT3 signaling pathway, regulation of RORγt and Foxp3 protein expression and modulation of the Th17/Treg balance.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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