Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

The characteristics of the frequent exacerbator with chronic bronchitis phenotype and non-exacerbator phenotype in patients with chronic obstructive pulmonary disease: a meta-analysis and system review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD. METHODS: CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3. RESULTS: Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent predicted (FEV1%pred) (mean difference (MD) -8.50, 95% CI -11.36--5.65, P < 0.001, I2 = 91%), forced vital capacity percent predicted (FVC%pred) [MD - 6.69, 95% confidence interval (CI) -7.73--5.65, P < 0.001, I2 = 5%], and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (MD -3.76, 95% CI -4.58--2.95,P < 0.001, I2 = 0%); in contrast, Charlson comorbidity index (MD 0.47, 95% CI 0.37-0.58, P < 0.001, I2 = 0], COPD assessment test (CAT) score (MD 5.61, 95% CI 4.62-6.60, P < 0.001, I2 = 80%), the quantity of cigarettes smoked (pack-years) (MD 3.09, 95% CI 1.60-4.58, P < 0.001, I2 = 41%), exacerbations in previous year (2.65, 95% CI 2.32-2.97, P < 0.001, I2 = 91%), modified Medical British Research Council (mMRC) score (MD 0.72, 95% CI 0.63-0.82, P < 0.001, I2 = 57%), and body mass index (BMI), obstruction, dyspnea, exacerbations (BODEx) (MD 1.78, 95% CI 1.28-2.28, P < 0.001, I2 = 91%), I2 = 34%) were significantly higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70-0.42, P = 0.62, I2 = 75%). CONCLUSION: COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.

Effect of acupoint application on T lymphocyte subsets in patients with chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD. METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis. RESULTS: Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4/CD8 ratio (MD 0.12, 95% CI 0.03-0.21, P < .01, I = 49%), reduce CD8 T-cells (MD-0.99, 95% CI-1.70-0.28, P < .001, I = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21, P < .001, I = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48, P < .001, I = 39%). CONCLUSION: Acupoint application can improve the CD4/CD8 ratio and CD8 T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.

The characteristics of the frequent exacerbators with chronic bronchitis phenotype and the asthma-chronic obstructive pulmonary disease overlap syndrome phenotype in chronic obstructive pulmonary disease patients: A meta-analysis and system review.

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Effect of Qigong on self-rating depression and anxiety scale scores of COPD patients: A meta-analysis.

OBJECTIVE: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD). METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis. RESULTS: Six studies (combined n = 415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P < .001, I = 69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P < .001, I = 15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P < .01, I = 0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P < .001, I = 0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P < .001, I = 0]; 6-minute walk test (6MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P < .001, I = 32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P < .05, I = 72%]. CONCLUSION: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6MWT distance, and SGRQ score.

[Analysis of clinical characteristics of traditional Chinese and Western medicine in Professor Jiang Liangduo's theory of "sanjiao meridian stasis"].

In the clinical practice, Professor Jiang Liangduo, a national senior Chinese medicine doctor, has created the theory of "sanjiao meridian stasis" from the theory of meridian dialectics and from the overall state. In this paper, the traditional Chinese medicine and Western medicine clinical characteristics of sanjiao meridian stasis theory which is often used by Professor Jiang Liangduo in the treatment of out-patient syndrome differentiation, were first studied and summarized to investigate its inherent regularity. First, the source of data and research methods were introduced, and then the Traditional Chinese Medicine Inheritance Support System was used with the method of data mining to retrospectively analyze the disease characteristics of Chinese and Western medicine in 279 patients with sanjiao meridian stasis diagnosed by Professor Jiang in 2014. Then the following main conclusions were made after research: sanjiao meridian stasis was more common in women as well as young and middle-aged population. Often manifested by prolonged treatment course, red tongue with yellowishfur, with good correlation between modern Western medicine diagnosis and TCM differentiation syndrome. The symptoms of sanjiao meridian stasis syndrome are mostly of heat syndromes, and middle-aged patients are the most common patients with stasis and stasis of sanjiao. Related information of Western medicine diagnosis can help to diagnose the "sanjiao meridian stasis".

[Mechanism of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture against influenza immune inflammatory injury].

OBJECTIVE: To observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on mRNA expression of lung inflammatory cytokines and pulmonary pathological injury of mice infected by influenza virus, in order to discuss the mechanism of tonifying Qi traditional Chinese medicines against pulmonary immune inflammatory injury of infected mice. METHOD: In different time phases after mice were infected with influenza virus FM1, the RT-PCR method was adopted to observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on five inflammatory cytokines TNF-α, IL-1, IL-6, IL-10 and IFN-γ, and the changes in pulmonary pathological injury of mice with viral pneumonia after intervention with tonifying qi traditional Chinese medicines. RESULT: (1) Tonifying Qi traditional Chinese medicines significantly reduced the mRNA expression of TNF-α at 1-5 d and IL-1 mRNA expression at 7 d, may increase IL-1 mRNA expression in mouse lung at 3 d, significantly reduced IL-6 mRNA expression in mouse lung and increased IL-10 mRNA expression at 3-7 d, and significantly increased IFN-γ mRNA expression at 1 d. (2) Tonifying Qi traditional Chinese medicines could significantly inhibited and repaired pulmonary immune inflammatory injury of mice infected by FM1, which was most remarkable at 3-7 d after the infection with influenza virus FM1. CONCLUSION: Tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture could resist pulmonary immune inflammatory injury and repair inflammatory injury by regulating the mRNA expression of imbalance inflammatory cytokines of organisms infected with influenza virus.

Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

[Effect of triangle drugs as ginseng, Trichosanthes kirilowii maxim and rhubarb on the level of blood lipids and related pro-inflammatory cytokines during the process of treating atherosclerosis].

OBJECTIVE: To study the effect of triangle drugs as ginseng, Trichosanthes kirilowii Maxim, and rhubarb on the levels of blood lipids as [total cholesterol (TC), triglyeride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] and pro-inflammatory cytokines as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and high sensitive C reactive protein (hs-CRP) during the process of treating atherosclerosis. METHODS: Twenty New Zealand rabbits were randomly divided into three groups after one-week adaptive feeding, i.e., the normal control group (n=6), the model group (n=6), and the triangle drugs group (n=8). High fat diet was fed to rabbits in the triangle drugs group and the model group at the daily dose of 100 g for six weeks. Iliac artery was injured in the model group and the triangle drugs group at the seventh week using balloon injury. High fat diet was successively fed to those after surgery for six weeks. At the same time of modeling, preventive medication (at the daily dose of dry ginseng 0.64 g/kg, Trichosanthes kirilowii Maxim 2.14 g/kg, and prepared Radix et Rhizoma Rhei with wine 0.43 g/kg, with the volume of 2 mL/kg) was administered by gastrogavage to rabbits in the triangle drugs group. Changes of blood lipids levels and related pro-inflammatory cytokines were dynamically observed. RESULTS: On the 7th week (before surgery), the levels of TC, TG, HDL-C, and LDL-C in the model group, TC, HDL-C, and LDL-C in the triangle drugs group significantly increased, showing significant difference when compared with those of the normal control group (P < 0.05). The levels of pro-inflammatory cytokines in the model group and the triangle drugs group were significantly higher than those in the normal control group (P < 0.05). Levels of TC, TG, and LDL-C were lower in the triangle drugs group than in the model group, showing statistical difference (P < 0.05). After the 8th week the levels of blood lipids and ICAM-1 in the model group, and levels of TC, LDL-C, HDL-C, and ICAM-1 in the triangle drugs group were significantly higher than those of the normal control group, showing statistical difference (P < 0.05). After the 12th week levels of blood lipids in the model group, LDL-C and HDL-C in the triangle drugs group were significantly higher than those of the normal control group, showing statistical difference (P < 0.05). The LDL-C level was lower in the triangle drugs group than in the model group, showing statistical difference (P < 0.05). The levels of VCAM-1, ICAM-1, and hs-CRP in the model group were obviously higher than those in the triangle drugs group and the normal control group, showing statistical significance (P < 0.05). The hs-CRP level was higher in the triangle drugs group than in the normal control group, showing statistical difference (P < 0.05). CONCLUSIONS: The triangle drugs may postpone the process of atherosclerosis by lowering blood lipids levels, especially by lowering the elevating levels of TC and LDL-C. Its roles in decreasing the level of pro-inflammatory cytokines might be associated with lipids lowering and anti-inflammation. Its roles may also be associated with improvement of the endothelial function and inhibition of the smooth muscle proliferation.

[Effects of tetramethylpyrazine on angiotensin II -induced proliferation and type I collagen synthesis of rat cardiac fibroblasts].

OBJECTIVE: To observe the effects of tetramethylpyrazine (TMP) on the proliferation and type I collagen synthesis of rat cardiac fibroblasts (CFBs) induced by angiotensin II (Ang II), and to explore the mechanism of TMP in treating myocardial fibrosis. METHODS: CFBs were isolated from neonatal rats, and the fourth-passage CFBs were used in the entire test and were stimulated by 0.1 micromol/L Ang II in vivo. The CFB proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay. Type I collagen in the cell culture supernatant was measured by enzyme-linked immunosorbent assay. The expression of mRNA of type I collagen was semi-quantitatively measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) In MTT assay, the optical density of CFBs cultured with 0.1 micromol/L Ang II was higher than that of the blank control cultured with 2% fetal bovine serum-Dulbecco's modified Eagle's medium (FBS-DMEM). The difference was statistically significant (P < 0.05). Both optical densities of CFBs cultured with 0.1 micromol/L Ang II plus 800 microg/mL TMP and 0.1 micromol/L Ang II plus 600 microg/mL TMP were lower than that of CFBs cultured with 0.1 micromol/L Ang II, but only the difference between 0.1 micromol/L AngII plus 800 microg/mL TMP group and 0.1 micromol/L Ang II group was significant (P < 0.05). (2) The content of type I collagen secreted by CFBs cultured with 0.1 micromol/L Ang II was higher than that with 2% FBS-DMEM (P < 0.01). The content of type I collagen secreted by CFBs cultured with 0.1 micromol/L Ang II plus 800 microg/mL TMP was lower than that with 0.1 micromol/L Ang II (P < 0.05). (3) The level of type I collagen mRNA in 0.1 micromol/L Ang II group was higher than that in blank control group, and lower than that in 0.1 micromol/L Ang II plus 800 microg/mL TMP group. Both the differences between 0.1 micromol/L Ang II group and the blank control group and between 0.1 micromol/L Ang II group and 0.1 micromol/L Ang II plus 800 microg/mL TMP group were statistically significant (P < 0.05). CONCLUSION: TMP can not only inhibit the proliferation of CFBs, but also decrease the secretion and the mRNA expression level of collagen I in cultured CFBs of rat which are increased by Ang II.

[Influence of Feixian Formula on serum transforming growth factor-beta1 and platelet-derived growth factor in rats with bleomycin-induced pulmonary fibrosis].

OBJECTIVE: To observe the effects of Feixian Formula, a compound traditional Chinese herbal medicine for treating pulmonary fibrosis, on bleomycin-induced pulmonary fibrosis in rats, and its influence on serum transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF). METHODS: Seventy-two male Wistar rats were infused with bleomycin (1 mg/kg) through tracheal intubation to induce pulmonary fibrosis, and they were randomly divided into untreated group (n=24), prednisone-treated group (n=24) and Feixian Formula-treated group (n=24). Fifteen male Wistar rats of the sham-operated group were infused with equivalent normal saline. Twenty-four hours after operation, prednisone (5 mg/kg) and Feixian Formula (1.25 g/kg) were given to the prednisone-treated group and Feixian Formula-treated group respectively by intragastric administration once a day. Equivalent saline was administered to rats of the untreated group and sham-operated group. On the 14th, 28th and 45th day, 5 rats in the sham-operated group and 8 rats in each of the other three groups were dissected to observe pathologic changes of the lung tissues, and the levels of serum TGF-beta1 and PDGF were determined by enzyme-linked immunosorbent assay. RESULTS: At the 45th day, the degree of pulmonary interstitial fibrosis was lesser in rats of the Feixian Formula-treated group as compared with those of the untreated group and prednisone-treated group. The levels of serum TGF-beta1 and PDGF were increased, and were significantly higher than those of the sham-operated group, especially on the 45th day (P<0.05). Changes of TGF-beta1 level in the prednisone-treated group and the Feixian Formula-treated group were similar to untreated group (P>0.05), and there was no significant difference between the prednisone-treated group and the Feixian Formula-treated group (P>0.05). PDGF in the Feixian Formula-treated group reached the highest level on the 14th day, significantly higher than those of the other three groups (P<0.01). Then it decreased, and was close to that of the sham-operated group on the 45th day (P=0.792). The levels of PDGF in untreated group and prednisone-treated group were increased depending on time, and were obviously higher than that of the sham-operated group on the 45th day (P<0.01). CONCLUSION: Feixian Formula can relieve bleomycin-induced pulmonary fibrosis in rats, and the mechanism of its action may be related to down-regulating serum PDGF.

[A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation].

OBJECTIVE: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM). METHOD: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg) of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor beta1(TGF-beta1) and platelet-derived growth factor (PDGF) in serum were measured on the 14th, 28th and 45th day of the experiment. RESULTS: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P<0.01). Twenty-one days after the experiment, the body weight was declined too, but there was no significant difference between the bleomycin-treated group and the sham-operated group (P>0.05). Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01), the level of serum TGF-beta1 began to increase since 28 days after the experiment (P<0.05, P<0.01), and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05). And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups. CONCLUSION: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.

[Effect of dongchong xiacao capsule on airway inflammation of asthmatic patients].

OBJECTIVE: To investigate the effect of dongchong xiacao capsule on the airway inflammation of asthmatic patients and to explore the relevant mechanism of therapeutic effect of Dongchongxiacao capsule. METHOD: Sixty patients with moderate persistent asthma were randomized into the treatment group (n=30) and the control group (n=30). Inhaled corticosteroid and as-needed beta-agonist were used in the treatment group while this therapy plus dongchong xiacao capsule were used in the control group for two months. Serum IL-4, IFN-gamma, sICAM-1, MMP-9, IgG, IgE level were assessed at randomization and 2 months after randomization. RESULT: The serum level of IgE, sICAM-1, IL-4 and MMP-9 of the treatment group was lowered to a greater degree than that of the control group (P < 0.05 or P < 0.01 ). CONCLUSION: Dongchong xiacao capsule can reduce the serum markers of airway inflammation, which suggests this therapy bares the anti-inflammation effects probably through regulating the balance of TH1/TH2, inhibiting the activity of adherence molecule and reducing IgE production. It may also have the effect of reversing airway remodeling, which needs further research to determine.

Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats.

AIM: To determine the dynamic changes in the expression of matrix metalloproteinases (MMPs) and the endogenous tissue inhibitors of MMPs inhibitors (TIMPs) during hepatic fibrosis induced by alcohol. METHODS: Male Sprague-Dawley rats were randomly divided into normal, 4 d, 2 wk, 4 wk, 9 wk and 11 wk groups, and the model rats were fed with a mixture of alcohol by gastric infusion at the designed time, respectively, then decollated and their livers were harvested for the examination of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1 and TIMP-2 by immunohistochemistry, zymograghy and Western blotting, respectively. RESULTS: Normal rats had moderate expression of MMP-2, which was decreased in the model rats except in the 11 wk group, where MMP-2 expression slightly increased. MMP-3 had the similar changing pattern to MMP-2 despite weaker expression. MMP-9 expression decreased in the 4 d and 2 wk groups, rose in the 4 wk group, decreased again in the 9 wk group and returned to normal levels in the 11 wk group. MMP-13 expression decreased in the 4 d and 2 wk groups, and returned to normal levels in the 4 wk, 9 wk and 11 wk groups. TIMP-1 expression decreased in the 4 d and 2 wk groups, but sharply increased in the 4 wk group and sustained at a high level even after modeling was stopped for 2 wk. In normal rats TIMP-2 expression was strong. However, it decreased as soon as modeling began, and then gradually rose, but remained to a level lower than that in normal rats even after modeling was stopped for 2 wk. CONCLUSION: MMP-2 may not always expresses at a high level during hepatic fibrosis. MMP-13 and MMP-3 are acutely affected by TIMP-1. In this model TIMP-1 is the most powerful factor imposed on capillarization and peri-sinusoidal fibrosis. TIMP-2 is the most effective regulator on the metabolism of type IV collagen located in the basement of sinus.

[Effect of safflower injection on cardiac energy charge and anti-apoptosis gene bcl-2 in rats' heart].

OBJECTIVE: To study the effect of safflower injection (SI) in protecting heart, and on energy charge and anti-apoptosis gen bcl-2 in cardiac tissue. METHODS: Rats' Langendorff isolated heart infused model was used in the experiment to study the effect of SI by measuring the cardiac function, energy charge and bcl-2 expression of the cultured heart in the modified Euro-Collins (mEC) heart preserving liquid with or without addition of SI. RESULTS: As compared with the control, SI showed the effects of improving functions of cardiac contraction and dilation, increasing coronary blood flow, and strengthening the bcl-2 protein expression. CONCLUSION: SI has excellent effect in protecting heart.

Dynamic changes of capillarization and peri-sinusoid fibrosis in alcoholic liver diseases.

AIM: To investigate the dynamic changes of capillarization and peri-sinusoid fibrosis in an alcoholic liver disease model induced by a new method. METHODS: Male SD rats were randomly divided into 6 groups, namely normal, 4 d, 2 w, 4 w, 9 w and 11 w groups. The animals were fed with a mixture of alcohol for designated days and then decollated, and their livers were harvested to examine the pathological changes of hepatocytes, hepatic stellate cells, sinusoidal endothelial cells, sinusoid, peri-sinusoid. The generation of three kinds of extra cellular matrix was also observed. RESULTS: The injury of hepatocytes became severer as modeling going on. Under electronic microscope, fatty vesicles and swollen mitochondria in hepatocytes, activated hepatic stellate cells with fibrils could been seen near or around it. Fenestrae of sinusoidal endothelial cells were decreased or disappeared, sinusoidal basement was formed. Under light microscopy typical peri-sinusoid fibrosis, gridding-like fibrosis, broaden portal areas, hepatocyte's fatty and balloon denaturation, iron sediment, dot necrosis, congregated lymphatic cells and leukocytes were observed. Type I collagen showed an increasing trend as modeling going on, slightly recovered when modeling stopped for 2 weeks. Meanwhile, type IV collagen decreased rapidly when modeling began and recovered after modeling stopped for 2 weeks. Laminin increased as soon as modeling began and did not recover when modeling stopped for 2 weeks. CONCLUSION: The pathological changes of the model were similar to that of human ALD, but mild in degree. It had typical peri-sinusoid fibrosis, however, capillarization seemed to be instable. It may be related with the reduction of type IV collagen in the basement of sinusoid during modeling.