AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided int...AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided into sham-operation group, model control group and Radix Astragali treatment group. On days 7, 14, 21 and 28 after operation, mortality rate of rats, pathological changes in immune organs, expression levels of Bax and nuclear factor (NF)-κB p65 proteins, apoptosis indexes and serum tumor necrosis factor (TNF)-α level in spleen and thymus were observed, respectively.RESULTS: Compared to model control group, the number of dead OJ rats in Radix Astragali treatment group decreased (P > 0.05). The TNF-α level (27.62 ± 12.61 vs 29.55 ± 18.02, 24.61 ± 9.09 vs 31.52 ± 10.95) on days 7 and 21, the pathological severity score for spleen [0.0 (0.0) vs 0.0 (2.0) on days 7 and 14 and for lymph nodes [0.0 (1.0) vs 1.0 (2.0), 1.0 (0.0) vs 2.0 (1.0)] on days 21 and 28, the product staining intensity and positive rate of Bax protein in spleen [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5) and thymus [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5)] on days 14 and 28, the apoptotic indexes [0.0 (0.0) vs 0.0 (0.01)] in spleen and thymus [0.0 (0.0) vs 0.0 (0.01) on days 14 and 21 were significantly lower in Radix Astragali treatment group than in model control group (P < 0.05). CONCLUSION: Radix Astragali has protective effects on immune organs of OJ rats by relieving the pathological changes in immune organs, reducing TNF-α level and inhibiting Bax expression and apoptosis in spleen and thymus.展开更多
The levels of lipopolysaccharide (LPS) induced interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL 6 and TNF ...The levels of lipopolysaccharide (LPS) induced interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL 6 and TNF α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL 6 or TNF α expression studied. Both IL 6 and TNF α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS induced IL 6 (787.82±151.97 pg/ml) and TNF α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL 6 (50.67±4.70 pg/ml) and TNF α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma: 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL 6 and TNF α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO 2 below 90 % in the total sleep time. It was concluded that LPS induced IL 6 and TNF α levels as well as plasma IL 6 and TNF α levels in the patients with OSAS were up regulated, which may be associated with the pathogenesis of OSAS.展开更多
Background Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anor...Background Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease （COPD）. Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-α （TNF-α）. This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-α. Methods Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups： group COPD IA （patients without malnutrition during acute exacerbation, n=25）, group COPD IB （patients without malnutrition during stable disease, n=29）, group COPD II （patients with malnutrition during stable disease, n=18）. To eliminate the effect of sex differences, all patients and controls were male. Body mass index （BMI）, percent ideal body weight （IBW%）, triceps skin-fold thickness （TSF）, mid-upper ann circumference （MAC）, mid-upper arm muscle circumference （MAMC）, serum leptin and TNF-α levels, serum prealbumin （PA）, serum transferrin （TF）, serum albumin （Alb）, total lymphocytes count （TLC）, forced expiratory volume in one second （FEV1）, maximal inspiration pressure （MIP） and maximal expiration pressure （MEP） were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-α levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed. Results Serum leptin levels were significantly lower in group COPD Ⅱ[（4.07 ±3.42） ng/ml] than in group COPD IB [（9.72± 6.67） ng/ml] and controls [（8.21 ±5.41） ng/ml] （P〈0.05）. There was no statistically significant difference in serum leptin levels between group COPD IA [（10.82±6.40） ng/ml], group COPD IB [（9.72±6.67） ng/ml] and controls [（8.21 ±5.41） ng/ml]. There was no statistically significant difference in serum TNF-α levels between group COPD Ⅱ[（8.03 ±3.37） pg/ml], group COPD IA [（8.90± 1.60） pg/ml], and group COPD IB [（7.25 ±2.08） pg/ml]. There was no significant correlation between leptin and TNF-α in any group. Conclusions Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-α and leptin during the regulation of the energy balance in COPD patients.展开更多
Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α...Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α） is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme （TACE） is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group （group C, n=10）, saline solution parallel group （group P, n=-8）, and normal control group （group N, n=-8）. Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N （P〈0.01）. The contents of TNF-α in serum （P〈0.01） and bronchoalveolar lavage fluid （BALF） （P〈0.01） were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α （r=0.784, P〈0.01） and between TACE and ErbB3 （r=0.526, P〈0.01） respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.展开更多
Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease （COPD）. Tumor necrosis factor alpha （TNF-α） is o...Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease （COPD）. Tumor necrosis factor alpha （TNF-α） is one of the most important cytokines which are involved in COPD. This study aimed at investigating the influence of its inhibitor, recombinant human necrosis factor-alpha receptor II：lgG Fc fusion protein （rhTNFR：Fc） on alveolar septal cell apoptosis in passive smoking rats. Methods Forty-eight rats were randomly divided into a normal control group, a passive smoking group, an rhTNFR：Fc intervention group and a sham intervention group. The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days. After smoking for one month the rhTNFR：Fc intervention group was treated with rhTNFR：Fc by subcutaneous injection, the sham intervention group injected subcutaneously with a neutral preparation （normal saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg as a control. Lung function was determined and the levels of TNF-a in serum and broncho-alveolar lavage fluid （BALF） were measured with enzyme-linked immunosorbnent assay （ELISA）. Lung tissue sections stained by hematoxylin and eosin （HE） were observed for study of morphological alternations. Mean linear intercept （MLI） and mean alveolar numbers （MAN） were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） method was carried out to determine the percentage of positive cells and distribution of apoptotic cells. Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR：Fc intervention group （P〈0.05）. Forced expiratory volume in 0.3 second （FEVo.3）/forced vital capacity （FVC） and peak expiratory flow （PEF） were lower in the passive smoking group than that in the normal control group （P〈0.05）. Compared with the sham intervention group, FEVo.3/FVC and PEF increased in the rhTNFR：Fc intervention group （P〈0.05）. The levels of TNF-α in serum were higher in the passive smoking group than that in the normal control group （P〈0.05） and rhTNFR：Fc intervention group （P〈0.05）. Significant differences were found between the levels of TNF-α in the serum of the rhTNFR：Fc intervention group and sham intervention group （P〈0.05）. The levels of TNF-α in BALF were higher in the passive smoking group than that in the normal control group （P〈0.05）, but no significant differences of TNF-α levels in BALF were found between the passive smoking group and rhTNFR：Fc intervention group. The number of TUNEL positive cells in alveolar septa was significantly increased in the passive smoking group as compared with the normal control group and the rhTNFR：Fc intervention group （P〈0.05）. Conclusion This study provides preliminary evidence that rhTNFR：Fc may interfere with TNF-α and reduce alveolar septal apoptosis in smoking rats.展开更多
基金Supported by Technological Foundation Project of Traditional Chinese Medicine of Zhejiang Province, No. 2003C130, No. 2004C142Foundation Project for Medical Science and Technology of Zhejiang Province, No. 2003B134+3 种基金Grave foundation project for Technology and Development of Hangzhou, No. 2003123B19Intensive Foundation Project for Technology of Hangzhou, No. 2004Z006Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided into sham-operation group, model control group and Radix Astragali treatment group. On days 7, 14, 21 and 28 after operation, mortality rate of rats, pathological changes in immune organs, expression levels of Bax and nuclear factor (NF)-κB p65 proteins, apoptosis indexes and serum tumor necrosis factor (TNF)-α level in spleen and thymus were observed, respectively.RESULTS: Compared to model control group, the number of dead OJ rats in Radix Astragali treatment group decreased (P > 0.05). The TNF-α level (27.62 ± 12.61 vs 29.55 ± 18.02, 24.61 ± 9.09 vs 31.52 ± 10.95) on days 7 and 21, the pathological severity score for spleen [0.0 (0.0) vs 0.0 (2.0) on days 7 and 14 and for lymph nodes [0.0 (1.0) vs 1.0 (2.0), 1.0 (0.0) vs 2.0 (1.0)] on days 21 and 28, the product staining intensity and positive rate of Bax protein in spleen [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5) and thymus [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5)] on days 14 and 28, the apoptotic indexes [0.0 (0.0) vs 0.0 (0.01)] in spleen and thymus [0.0 (0.0) vs 0.0 (0.01) on days 14 and 21 were significantly lower in Radix Astragali treatment group than in model control group (P < 0.05). CONCLUSION: Radix Astragali has protective effects on immune organs of OJ rats by relieving the pathological changes in immune organs, reducing TNF-α level and inhibiting Bax expression and apoptosis in spleen and thymus.
文摘The levels of lipopolysaccharide (LPS) induced interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL 6 and TNF α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL 6 or TNF α expression studied. Both IL 6 and TNF α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS induced IL 6 (787.82±151.97 pg/ml) and TNF α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL 6 (50.67±4.70 pg/ml) and TNF α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma: 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL 6 and TNF α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO 2 below 90 % in the total sleep time. It was concluded that LPS induced IL 6 and TNF α levels as well as plasma IL 6 and TNF α levels in the patients with OSAS were up regulated, which may be associated with the pathogenesis of OSAS.
文摘Background Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease （COPD）. Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-α （TNF-α）. This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-α. Methods Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups： group COPD IA （patients without malnutrition during acute exacerbation, n=25）, group COPD IB （patients without malnutrition during stable disease, n=29）, group COPD II （patients with malnutrition during stable disease, n=18）. To eliminate the effect of sex differences, all patients and controls were male. Body mass index （BMI）, percent ideal body weight （IBW%）, triceps skin-fold thickness （TSF）, mid-upper ann circumference （MAC）, mid-upper arm muscle circumference （MAMC）, serum leptin and TNF-α levels, serum prealbumin （PA）, serum transferrin （TF）, serum albumin （Alb）, total lymphocytes count （TLC）, forced expiratory volume in one second （FEV1）, maximal inspiration pressure （MIP） and maximal expiration pressure （MEP） were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-α levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed. Results Serum leptin levels were significantly lower in group COPD Ⅱ[（4.07 ±3.42） ng/ml] than in group COPD IB [（9.72± 6.67） ng/ml] and controls [（8.21 ±5.41） ng/ml] （P〈0.05）. There was no statistically significant difference in serum leptin levels between group COPD IA [（10.82±6.40） ng/ml], group COPD IB [（9.72±6.67） ng/ml] and controls [（8.21 ±5.41） ng/ml]. There was no statistically significant difference in serum TNF-α levels between group COPD Ⅱ[（8.03 ±3.37） pg/ml], group COPD IA [（8.90± 1.60） pg/ml], and group COPD IB [（7.25 ±2.08） pg/ml]. There was no significant correlation between leptin and TNF-α in any group. Conclusions Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-α and leptin during the regulation of the energy balance in COPD patients.
文摘Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α） is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme （TACE） is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group （group C, n=10）, saline solution parallel group （group P, n=-8）, and normal control group （group N, n=-8）. Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N （P〈0.01）. The contents of TNF-α in serum （P〈0.01） and bronchoalveolar lavage fluid （BALF） （P〈0.01） were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α （r=0.784, P〈0.01） and between TACE and ErbB3 （r=0.526, P〈0.01） respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.
基金This-study was supported by the grants from National Natural Science Foundation of China （No. 30770931）, Research Fund of National Education Ministry of China （No. 200050533023） and Research Fund for Reform of Postgraduate Education in Hunan Province （No. 06B07）.
文摘Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease （COPD）. Tumor necrosis factor alpha （TNF-α） is one of the most important cytokines which are involved in COPD. This study aimed at investigating the influence of its inhibitor, recombinant human necrosis factor-alpha receptor II：lgG Fc fusion protein （rhTNFR：Fc） on alveolar septal cell apoptosis in passive smoking rats. Methods Forty-eight rats were randomly divided into a normal control group, a passive smoking group, an rhTNFR：Fc intervention group and a sham intervention group. The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days. After smoking for one month the rhTNFR：Fc intervention group was treated with rhTNFR：Fc by subcutaneous injection, the sham intervention group injected subcutaneously with a neutral preparation （normal saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg as a control. Lung function was determined and the levels of TNF-a in serum and broncho-alveolar lavage fluid （BALF） were measured with enzyme-linked immunosorbnent assay （ELISA）. Lung tissue sections stained by hematoxylin and eosin （HE） were observed for study of morphological alternations. Mean linear intercept （MLI） and mean alveolar numbers （MAN） were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） method was carried out to determine the percentage of positive cells and distribution of apoptotic cells. Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR：Fc intervention group （P〈0.05）. Forced expiratory volume in 0.3 second （FEVo.3）/forced vital capacity （FVC） and peak expiratory flow （PEF） were lower in the passive smoking group than that in the normal control group （P〈0.05）. Compared with the sham intervention group, FEVo.3/FVC and PEF increased in the rhTNFR：Fc intervention group （P〈0.05）. The levels of TNF-α in serum were higher in the passive smoking group than that in the normal control group （P〈0.05） and rhTNFR：Fc intervention group （P〈0.05）. Significant differences were found between the levels of TNF-α in the serum of the rhTNFR：Fc intervention group and sham intervention group （P〈0.05）. The levels of TNF-α in BALF were higher in the passive smoking group than that in the normal control group （P〈0.05）, but no significant differences of TNF-α levels in BALF were found between the passive smoking group and rhTNFR：Fc intervention group. The number of TUNEL positive cells in alveolar septa was significantly increased in the passive smoking group as compared with the normal control group and the rhTNFR：Fc intervention group （P〈0.05）. Conclusion This study provides preliminary evidence that rhTNFR：Fc may interfere with TNF-α and reduce alveolar septal apoptosis in smoking rats.
