ABSTRACT
ObjectiveTo investigate the regulatory effects of traditional Chinese medicine (TCM) Shufengxuanfeijiedu formula on Janus kinase signal transducer and activators of transcription (JAK-STAT) of lung tissues in mice with influenza viral pneumonia.Methods According to random number table, 60 mice were randomly divided into six groups with 10 mice in each group: normal group (N), model group (M), Tamiflu control group (C) and low (SL), medium (SM), high dose (SH) Shufengxuanfeijiedu formula groups. The mouse model of influenza virus pneumonia was reproduced by dropping of 0.05 mL 4LD50 inflluenza virus FM1 strain which can be adapted to lung tissue into the nose; while the N received nose instillation of 0.05 mL normal saline. After successful modeling for 2 hours, distilled water was given orally (by lavage) to N and M; Duffy (oseltamivir) 2.5 g·mL-1·d-1 was administrated to C; the TCM SL, SM, SH were intragastrically administered with different doses of shufengxuanfeijiedu decoction into the corresponding groups respectively (the ingredients of prescription: chrysanthemum, mulberry leaf, almond, platycodon root, forsythia, bupleurum etc. forming granules), according to the suitable dose of granules used for human body surface, the dose used for mouse surface area was calculated, the high dose means the dose used in the medium dose group doubled, the low dose means 1/2 dose used in medium group, once a day, once 0.2 mL for consecutive 4 days. Afterwards, the lung tissues were collected, the mouse differential gene expressions related to JAK-STAT pathway were detected by gene chip technology, the standards for screening of differential gene expression were as follows: up-regulated gene was P 1; down-regulation gene wasP < 0.05, and log2ratio < -1. The levels in lung tissue kinase (JAK) andγinterferon (IFN-γ) mRNA expressions were determined by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results Compared with those in N, the differential expression gene transcription activator, STAT5 [log2 (N/M) = 2.32], interleukin 4 receptor alpha subunit [IL4RA, log2 (N/M) = 4.77], interleukin 12 receptor [IL12R, log2 (N/M) = 1.58], JAK [log2 (N/M) = 2.41] were all obviously up-regulated, and IFN was significantly down-regulated [log2 (N/M) = -1.45] in M. Compared with those in M, C group IFN [log2 (C/M) = 1.51], various TCM dose groups [log2 (SL/M) = 1.46, log2 (SM/M) = 1.72, log2 (SH/M) = 1.40] differential expression gene IFN was significantly up-regulated, STAT5 [log2 (C/M) = -2.06, log2 (SL/M) = -1.41, log2 (SM/M) = -2.10, log2 (SH/M) = -1.89], IL4RA [log2 (C/M) = -2.52, log2 (SL/M) = -1.85, log2 (SM/M) = -2.74, log2 (SH/M) = -1.39), IL12R [log2 (C/M) = -1.48, log2 (SL/M) = -0.10, log2 (SM/M) = -1.58, log2 (SH/M) = -0.53], JAK [log2 (C/M) = -1.44, log2 (SL/M) = -0.88, log2 (SM/M) = -1.74, log2 (SH/M) = -0.53] were significantly down-regulated. In M, the JAK mRNA expression was obviously elevated (2-ΔΔCt: 3.17±0.94 vs. 1.01±0.13,P < 0.05), while the IFN-γ mRNA expression was decreased (2-ΔΔCt: 0.15±0.48 vs. 1.01±0.12,P < 0.05); compared with M, the JAK mRNA expressions in C, SM and SH groups were all obviously decreased (2-ΔΔCt: 2.02±0.63, 1.19±0.30, 1.59±0.67 vs. 3.17±0.94, allP < 0.05); while the IFN-γmRNA expressions in C, SL, SM and SH groups were elevated (2-ΔΔCt: 0.61±0.12, 0.41±0.13, 0.85±0.14, 0.78±0.20 vs. 0.15±0.48, allP < 0.05).Conclusions Shufengxuanfeijiedu formula can ameliorate the mice immune pathological injury of lung tissues induced by influenza virus by regulating JAK-STAT signal pathway and balancing Th1/2 via up-regulating the expression of IFN-γ.