Electroacupuncture at ST36 (Zusanli) Prevents T-Cell Lymphopenia and Improves Survival in Septic Mice.

Purpose: Sepsis is the main cause of death in intensive care unit. Maladaptive cytokine storm and T-cell lymphopenia are critical prognosis predictors of sepsis. Electroacupuncture (EA) is expected to be an effective intervention to prevent sepsis. This study aims to determine the potential of EA at ST36 (Zusanli) to prevent experimental septic mice. Methods: Mice were randomly assigned into PBS, LPS, or EA+LPS group. EA (0.1 mA, continuous wave, 10 Hz) was performed stimulating the ST36 for 30 min, once a day for 3 days. After the third day, all mice were challenged with PBS or LPS (4 mg/kg) simultaneously. Mice were evaluated for survival, ear temperature, and other clinical symptoms. Lung and small intestine tissue injuries were analyzed by hematoxylin and eosin staining. Bio-Plex cytokine assay was used to analyze the concentration of cytokines. T lymphocytes were analyzed by flow cytometry and Western blot assays. The role of T cells in preventing sepsis by EA was analyzed by using nude mice lacking T lymphocytes. Results: EA at ST36 improved survival, symptom scores, and ear temperature of endotoxemic mice. EA also improved dramatically pulmonary and intestinal injury by over 50% as compared to untreated mice. EA blunted the inflammatory cytokine storm by inducing a lasting inhibition of the production of major inflammatory factors (TNF-α, IL-1ß, IL-5, IL-6, IL-10, IL-17A, eotaxin, IFN-γ, MIP-1ß and KC). Flow cytometry and Western blot analyses showed EA significantly reduced T-lymphocyte apoptosis and pyroptosis. Furthermore, T lymphocytes were critical for the effects of EA at ST36 stimulation blunted serum TNF-α levels in wild-type but not in nude mice. Conclusion: EA halted systemic inflammation and improved survival in endotoxemic mice. These effects are associated with the protective effect of EA on T lymphocytes, and T cells are required in the anti-inflammatory effects of EA in sepsis.

Analysis of Acupoint Selection and Combinations in Acupuncture Treatment of Asthma Based on Data Mining.

OBJECTIVE: Asthma is a highly prevalent respiratory disease that remains difficult to control. Acupuncture, as an important alternative therapeutic modality in preventing and treating asthma, is widely used in the world due to its promising efficacy and safety. Although acupoint selection and combinations are critical to therapeutic effects of acupuncture, its fundamental rules for asthma have not been fully understood. Thus, using data mining, the present study aimed to discover the most effective acupoints and combinations in the acupuncture treatment of asthma. METHODS: Controlled clinical trials (CCTs) of acupuncture treatment for asthma were searched and retrieved from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and PubMed. Data regarding the main acupoints prescribed in these clinical trials was collected and quantified. A network analysis was performed to uncover the interconnections between the acupoints. Additionally, hierarchical clustering analysis and association rule mining were conducted to discover the potential acupoint combinations. RESULTS: A total of 183 CCTs were retrieved. Feishu (BL13), Dingchuan (EX-B1), Dazhui (GV14), Shengshu (BL23), Pishu (BL20), and Fengmen (BL12) appeared to be the most frequently used acupoints for asthma. While the Bladder Meridian of Foot Taiyang, the Governor Vessel, and the Conception Vessel, compared to other meridians, were found to be the more commonly selected meridians. In the acupoint interconnection network, Feishu (BL13), Fengmen (BL12), Dingchuan (EX-B1), and Dazhui (GV14) were defined as key node acupoints. Moreover, acupoint clustering analysis revealed the treatment principle of "facilitating the flow of the lung Qi, tonifying spleen and kidney, and treating both the symptoms and root causes." Association rule mining analysis demonstrated that the combination of Pishu, Shenshu, Feishu, and Dingchuan, as well as that of Feishu, Dazhui, and Fengmen were potential acupoint combinations that should be selected with priority in asthma treatment. CONCLUSION: Based on a data mining analysis of published CCTs, this study provides valuable information regarding the selection of the most effective acupoints and combinations for clinical acupuncture practice and experimental study aimed at the prevention and treatment of asthma.

Acupuncture in a Rat Model of Asthma.

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.

G protein-coupled estrogen receptor, a potential therapeutic target of asthma probed by Chinese herb.

Discussion on the identification of GPER as a potential therapeutic target for asthma through Chinese herb-driven drug discovery strategy.

Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas.

ETHNOPHARMACOLOGICAL RELEVANCE: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments. AIM OF THE STUDY: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy. MATERIALS AND METHODS: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated. RESULTS: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10-2 mM) and ginkgolide A (1 × 10-5 mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 µg/kg) and ginkgolide A (205 µg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6). CONCLUSION: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy.

Metallothionein-2 is associated with the amelioration of asthmatic pulmonary function by acupuncture through protein phosphorylation.

BACKGROUND: Acupuncture has long been used for asthma treatment but the underlying mechanism remains unclear. Previous study showed that metallothionein-2 (MT-2) was significantly decreased in asthmatic lung tissue. However, the relationship between acupuncture treatment and MT-2 expression during asthma is still unknown, and the detailed effect analysis of MT-2 on phosphorylation in airway smooth muscle cells (ASMCs) is also unclear. METHODS: The acupuncture effect on pulmonary resistance (RL) was investigated in a rat model of asthma, and the mRNA and protein levels of MT-2 in lung tissue were detected. Primary ASMCs were isolated and treated with MT-2 recombinant protein to study the MT-2 effects on ASMC relaxation. A Phospho Explorer antibody microarray was applied to detect protein phosphorylation changes associated with MT-2-induced ASMC relaxation. Bioinformatic analysis were performed with PANTHER database, DAVID and STRING. Phosphorylation changes in key proteins were confirmed by Western blot. RESULTS: Acupuncture significantly reduced RL at 2-5 min (P < 0.05 vs asthma) in asthmatic rats. Acupuncture continued to increase MT-2 mRNA expression in lung tissue for up to 14 days (P < 0.05 vs asthma). The MT-2 protein expression was significantly decreased in the asthmatic rats (P < 0.05 vs control), while MT-2 protein expression was significantly increased in the asthmatic model group treated with acupuncture (P < 0.05 vs asthma). Primary ASMCs were successfully isolated and recombinant MT-2 protein (100, 200, 400 ng/ml) significantly relaxed ASMCs (P < 0.05 vs control). MT-2 induced phosphorylation changes in 51 proteins. Phosphorylation of 14 proteins were upregulated while 37 proteins were downregulated. PANTHER classification revealed eleven functional groups, and the phosphorylated proteins were identified as transferases (27.8 %), calcium-binding proteins (11.1 %), etc. DAVID functional classification showed that the phosphorylated proteins could be attributed to eight functions, including protein phosphorylation and regulation of GTPase activity. STRING protein-protein interaction network analysis showed that Akt1 was one of the most important hubs for the phosphorylated proteins. The phosphorylation changes of Akt1 and CaMK2ß were consistent in both the Phospho Explorer antibody microarray and Western blot. CONCLUSION: Acupuncture can significantly ameliorate RL, and the MT-2 mRNA and protein levels in lung tissue are increased during treatment. MT-2 significantly relaxes ASMCs and induces a series of protein phosphorylation. These phosphorylation changes, including Akt1 and CaMK2ß, may play important roles in the therapeutic effects of acupuncture on asthma.

Acupuncture has a positive effect on asthmatic rats in a glucocorticoid-independent manner.

BACKGROUND: There is some evidence to support the use of acupuncture as an alternative therapy for asthma. However, the mechanisms underlying its effects are not fully understood. We have reported previously that acupuncture has beneficial effects on asthma without changing the concentration of serum cortisol, although endogenous glucocorticoid (GC) plays an important role in regulating immune responses. OBJECTIVE: In this study, bilateral adrenalectomy (removal of both adrenal glands) was performed in rats before asthma model induction to investigate whether acupuncture influences asthma in a GC-dependent manner. METHODS: Adrenal-intact and adrenalectomised rats were injected with ovalbumin to induce asthma and then left untreated or treated with manual acupuncture (MA) at GV14, bilateral BL12 and bilateral BL13, or manual restraint without MA. Healthy and sham-adrenalectomised control groups were also included. Pulmonary resistance (RL), serum concentrations of corticosterone, and eosinophil counts were measured at the end of the experimental course. Sera from adrenal-intact and adrenalectomised asthmatic rats treated with acupuncture were injected into untreated adrenal-intact and adrenalectomised asthmatic rats to investigate further the potential role of GC in the effect of acupuncture. RESULTS: Acupuncture significantly decreased RL and eosinophil count in both adrenal-intact and adrenalectomised asthmatic rats. Moreover, administration of sera derived from acupuncture-treated adrenal-intact and adrenalectomised asthmatic rats attenuated the increase in RL and eosinophil count in both asthmatic models. CONCLUSIONS: Results of this study suggest that endogenous GC is not a key contributor to the effects of acupuncture on asthma, and that acupuncture may have potentially therapeutic effects on asthma in a GC-independent manner.

Efficacy of acupuncture for chronic asthma: study protocol for a randomized controlled trial.

BACKGROUND: Although asthma symptoms can be temporarily controlled, it is recommended to use effective low-risk, non-drug strategies to constitute a significant advance in asthma management. Acupuncture has been traditionally used to treat asthma; however, the evidence for the efficacy of this treatment is still lacking. Previous clinical trials of acupuncture in treating asthma were limited by methodological defects; therefore, high-quality research is required. METHODS/DESIGN: This trial is designed as a multi-center, randomized, double-blind, parallel-group controlled trial. Patients with mild to moderate asthma will be randomly allocated to either a verum acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group or a sham acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group. Acupoints used in the verum acupuncture group are GV14 (Da Zhui), BL12 (Feng Men), BL13 (Fei Shu) and acupoints used in the sham acupuncture group are DU08 (Jin Suo), BL18 (Gan Shu), BL19 (Dan Shu). After a baseline period of 1 week, the patients in both groups will receive verum/sham acupuncture once every other day with a total of 20 treatment sessions in 6 weeks and a 3-month follow-up. The primary outcome will be measured by using the asthma control test and the secondary outcomes will be measured by using the percentage of symptom-free days, the average dosage of salbutamol aerosol and/or prednisone tablets, lung functions, daily asthma symptom scores, asthma quality of life questionnaire, and so on. DISCUSSION: This trial will assess the effect of acupuncture on asthma and aims to provide reliable clinical evidence for the efficacy of acupuncture in treating asthma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01931696 , registered on 26 August 2013.

Non-specific physiological background effects of acupuncture revealed by proteomic analysis in normal rats.

BACKGROUND: The total effects of adequate real acupuncture treatment consist of pathologic-specific and non-specific physiological effects. The latter may be the fundamental component of the therapeutic effects of acupuncture. This study investigated the physiological background effects of acupuncture in normal rats treated with acupuncture. METHODS: Manual acupuncture was performed on normal rats at experienced acupoints, GV14 (Dazhui), BL12 (Fengmen) and BL13 (Feishu), once every other day for two weeks. The proteomic profile of rat lung tissue was examined using 2-DE/MS-based proteomic techniques. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed for differentially expressed proteins using the WebGestalt toolkit. RESULTS: In total, 25 differentially expressed protein spots were detected in the 2-DE gels. Among these spots, 24 corresponded to 20 unique proteins that were successfully identified using mass spectrometry. Subsequent GO and KEGG pathway analyses demonstrated that these altered proteins were mainly involved in biological processes, such as 'protein stabilization', 'glycolysis/gluconeogenesis' and 'response to stimulus'. CONCLUSIONS: Our study indicated the non-specific background effects of acupuncture at acupoints GV14, BL12 and BL13 likely maintained internal homeostasis via regulation of the local stimulus response, energy metabolism, and biomolecule function balance, which may be important contributors to the therapeutic effects of acupuncture.

The research of acupuncture effective biomolecules: retrospect and prospect.

Acupuncture is an effective, safe and convenient therapy that has been applied for 2,500 years. The acupuncture researches have obtained significant improvement with the technical support of the life sciences and the studies of acupuncture have in turn accelerated the development of biomedical science. The effects of acupuncture influence important physiopathologic and biological activities, including gene expression, protein-protein interactions, and other biological processes. Cerebrospinal fluid, serum, organs, and tissues are reported to be carriers of the biomolecules of the effects of acupuncture. The paper summarized the progress of acupuncture effective biomolecules researches and found that biomolecules play important roles in the mechanism of acupuncture. With the development of omics technologies and translational medicine, the acupuncture research will meet both opportunities and challenges.

An In Vivo and In Vitro Evaluation of the Mutual Interactions between the Lung and the Large Intestine.

One of the most important theories of the traditional Chinese medicine is the exterior-interior relationship between the lung and the large intestine; so far, little direct experimental evidence has been reported to support such relationship. Here we for the first time investigated the mutual interactions between the lung and the large intestine by examining the relevancies between the pulmonary functions and the rectal resting pressure in the rat models of asthma and constipation. We also evaluated the effects of the lung homogenate and the large intestine homogenate on the isolated large intestine muscle strip and the isolated tracheal spiral, respectively. Our results showed that the pulmonary resistance and pulmonary compliance were closely related to the rectal resting pressure in the asthmatic rat model, while the rectal resting pressure was much correlated with the pulmonary resistance in the rat model of constipation. Moreover, it was shown that the lung homogenate could specifically contract the isolated large intestine muscle strip. Overall, this study provided new lines of evidence for the theory and highlighted the potential application in the treatment of the corresponding diseases.

Considerations for use of acupuncture as supplemental therapy for patients with allergic asthma.

This study examines the clinical and immunomodulatory effects of acupuncture in the treatment of patients with allergic asthma. The acupuncture points GV14, BL12, and BL13 were selected based on the theory of traditional Chinese medicine in treating asthma. Manual acupuncture was performed once every other day (three times per week) for 5 weeks. The needles were twisted approximately 360° evenly at the rate of 60 times/min for 20 s, manipulated every 10 min and withdrawn after 30 min. Concentrations of sIgA and total IgA in secretions were determined by the combination of sucrose density gradient ultracentrifugation and RIA. Levels of cortisol in the plasma were measured by RIA. Total IgE in the sera was examined by ELISA. Flow cytometry was used to detect the numbers of CD3+, CD4+, CD8+, and IL-2R + T lymphocytes in the peripheral blood. The absolute and differential numbers of eosinophils in peripheral blood were counted with eosin staining. The total efficacy of the acupuncture treatment in patients with allergic asthma at the end of one course of treatment was 85 %. After treatment, the concentrations of sIgA and total IgA in the saliva (P<0.01, P<0.02) and nasal secretions (P<0.02, P<0.02) were significantly decreased in patients with allergic asthma. The levels of total IgE in sera (P<0.001), the counts of IL-2R + T lymphocytes (P<0.001), and the absolute and differential numbers of eosinophils (P<0.01, P<0.01) in the peripheral blood were also significantly decreased. The numbers of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were significantly increased in the allergic asthmatics treated by acupuncture (P<0.001, P<0.01, and P<0.001, respectively). The concentration of cortisol in the plasma of asthmatic patients did not change significantly after the acupuncture treatment (P>0.05). Acupuncture has regulatory effects on mucosal and cellular immunity in patients with allergic asthma and may be an adjunctive therapy for allergic asthma.

[Influence of acupuncture on expression of T-type calcium channel protein in airway smooth muscle cell in airway remodeling rats with asthma].

OBJECTIVE: To observe the anti-remodeling effect of acupuncture on asthma and to explore the mechanism of T-type calcium channel protein in airway smooth muscle cell in airway remodeling effect in asthma. METHODS: Thirty-two rats were randomly divided into a normal group, a model group, an acupuncture group and a sham acupuncture group, 8 rats in each group. The rats in the latter three groups were sensitized for consecutive 14 days by single peritoneal injection of aqueous suspension 1 mL of 10 mg ovalbumin (OVA), 200 mg aluminum hydroxide and saline together with 1 mL inactivated pertussis vaccine. From the 15th day, asthma was induced for 30 minutes by ultrasonic atomizing inhalation of 1% OVA for consecutive 14 days in the model group. The acupuncture group was treated with acupuncture at "Dazhui" (GV 14), "Fengmen" (BL 12) and "Feishu" (BL 13) for 30 minutes before the ultrasonic atomizing inhalation, once every two days for consecutive 14 days. The same acupoints selection and the course of treatment as the acupuncture group were produced in the sham acupuncture group and they were treated with acupuncture at 1 mm acupoint skin without retaining needles. The normal group remained unhandled. The respiratory function and the airway remodeling were evaluated by airway resistance and pulmonary histopathology, respectively, and the T-type calcium channel protein expression of Ca(v)3.1, Ca(v) 3.2, Ca, 3.3 in airway smooth muscle cell were detected by immunohistochemistry technique. RESULTS: (1) The airway resistance in the model group was higher than that in the normal group and in the acupuncture group (both P < 0.05), and the airway resistance in the acupuncture group was lower than that in the sham acupuncture group (P < 0.05). (2) The ratios of the airway wall thickness to the basement membrane perimeter (Awt/Pbm) and the airway outer perimenter to the airway internal perimeter (Po/Pi) in the model group were higher than those in the normal group and in the acupuncture group (all P < 0.05), and the ratios of Awt/Pbm and Po/Pi in the acupuncture group were lower than those in the sham acupuncture group (both P < 0.05). (3) The average optical of Ca(v) 3.1 and Ca(v) 3.2 in airway smooth muscle cell in the model group were higher than that in the normal group and in the acupuncture group (both P < 0.05), and the average optical of Ca(v) 3.3 in airway smooth muscle cell in the model group was higher than that in the normal group (P < 0.05) and it was lower than that in the sham acupuncture group (P < 0.05). CONCLUSION: Acupuncture can inhibit the airway remodeling and the accrementition of the airway smooth muscle and can reduce the airway resistance. The mechanism may be related to the inhibition of T-type calcium channel protein in airway smooth muscle cell, especially in relation to the protein expression of Ca(v) 3.1.

Effects of acupuncture on the gene expression profile of lung tissue from normal rats.

Acupuncture has been demonstrated to be an effective treatment for various diseases. However, little attention has been paid to its physiological influences, especially on the changes in protein and mRNA levels following acupuncture treatment under normal conditions. In this study, we investigated the gene expression profile of lung tissue from acupuncture-treated normal rats and attempted to characterize the underlying mechanisms of the changes in expression. Three common acupoints, Dazhui (GV14), fengmen (BL12) and feishu (BL13) were selected for analysis, and 2 serial analyses of gene expression (SAGE) tag libraries of the lung tissues that were derived from the normal and acupuncture-treated rats were established. Bioinformatic analyses were carried out using the functional annotation tools of the database for annotation, visualization and integrated discovery (DAVID), the gene ontology (GO) Tree Machine and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. In total, 144 tags were differentially expressed (P<0.05), and the DAVID functional classification of genes demonstrated that the genes were divided into 6 types. Furthermore, GO Tree Machine analysis of the gene categories indicated that 10 enriched GO categories had become enriched after acupuncture, and that 15 KEGG pathways matched the differentially expressed tags of the 2 SAGE libraries. Our results show that the essential effects of acupuncture on normal rats include the regulation of macromolecular biosynthesis, transportation and metabolism. Cellular biosynthesis and cellular lipid metabolism are the common biological processes that occur in response to acupuncture under normal and morbid conditions, which may be the general physiological effects of acupuncture.

Proteomic analysis reveals the deregulation of inflammation-related proteins in acupuncture-treated rats with asthma onset.

Although the beneficial effects of acupuncture in asthma treatment have been well documented, little is known regarding the biological basis of this treatment. Changes in the lung proteome of acupuncture-treated rats with asthma onset were comparatively analyzed using a two-dimensional gel electrophoresis (2DE) and mass-spectrometry- (MS-) based proteomic approach. Acupuncture on specific acupuncture points appeared to improve respiratory function and reduce the total number of leukocytes and eosinophils in bronchoalveolar lavage fluid in OVA-induced asthma onset. Image analysis of 2DE gels revealed 32 differentially expressed acupuncture-specific protein spots in asthma onset; 30 of which were successfully identified as 28 unique proteins using LC-MS/MS. Bioinformatic analyses indicated that these altered proteins are most likely involved in inflammation-related biological functions, and the functional associations of these proteins result in an inflammation signaling pathway. Acupuncture regulates the pathway at different levels by regulating several key nodal proteins, including downregulating of proinflammatory proteins (e.g., S100A8, RAGE, and S100A11) and upregulating of anti-inflammatory proteins (e.g., CC10, ANXA5, and sRAGE). These deregulated inflammation-related proteins may mediate, at least in part, the antiasthmatic effect of acupuncture. Further functional investigation of these acupuncture-specific effector proteins could identify new drug candidates for the prophylaxis and treatment of asthma.

Use of serial analysis of gene expression to reveal the specific regulation of gene expression profile in asthmatic rats treated by acupuncture.

BACKGROUND: Asthma has become an important public health issue and approximately 300 million people have suffered from the disease worldwide. Nowadays, the use of acupuncture in asthma is increasing. This study intended to systematically analyze and compare the gene expression profiles between the asthmatic and acupuncture-treated asthmatic rat lung, and tried to gain insight into the molecular mechanism underlying the early airway response (EAR) phase of asthma treated by acupuncture. METHODS: Four tag libraries of serial analysis of gene expression (SAGE) were established from lung tissues of control rats (CK), asthmatic rats (AS), asthmatic rats treated by acupuncture (ASAC), and control rats treated by acupuncture (CKAC). Bioinformatic analyses were carried out by using the methods including unsupervised hierarchical clustering, functional annotation tool of the database for annotation, visualization, and integrated discovery (DAVID), gene ontology (GO) tree machine, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. RESULTS: There were totally 186 differentially expressed tags (P < 0.05, P(CK/AS)) between the libraries of CK and AS, 130 differentially expressed tags between libraries of AS/ASAC (P < 0.05, P(AS/ASAC)), and 144 differentially expressed tags between libraries of CK/CKAC (P < 0.05, P(CK/CKAC)). The gene expression profiles of AS and ASAC were more similar than other libraries via unsupervised SAGE clustering. By comparison of P(CK/AS) and P(AS/ASAC), the DAVID genes functional classification was found to be changed from "immune response" to "response to steroid hormone stimulus", and the GO term "antigen processing and presentation of peptide antigen" disappeared in P(AS/ASAC). Totally 3 same KEGG pathways were found among the three groups. Moreover, 21 specific tags of the acupuncture in treating asthma were detected using Venn diagrams. CONCLUSION: Our SAGE research indicates that the gene expression profile of the EAR phase of asthma could be effectively and specifically regulated by acupuncture, which suggests that the gene expression of immune response and steroid hormone may play an important role in the treatment.