Mice preantral follicles were cultured in vitro for 12 days to achieve metaphase Ⅱ (M Ⅱ ) oocytes. Oocyte growth differentiation factor-9 (GDF-9) gene expression was measured during different growth stages to ex...Mice preantral follicles were cultured in vitro for 12 days to achieve metaphase Ⅱ (M Ⅱ ) oocytes. Oocyte growth differentiation factor-9 (GDF-9) gene expression was measured during different growth stages to explore the relationship between oocyte maturation and GDF-9 gene expression. Preantral follicles of lO-day old mice were isolated from the ovaries and were cultured for 12 days. Oocytes from day 2 (D2), D4, D6, D8, DIO, D12 cultured in vitro were named the in vitro group and oocytes of day 12 (D12), D14, D16, D18, D20, D22 grown in vivo were named the in vivo group. Follicle survival, antrum formation and maturation rate were 89.5%, 51.8% and 56.6% respectively in follicles cultured in vitro. After RT-PCR and agarose gel electrophoresis, relative mRNA abundance of GDF-9 was measured in each group of oocytes. At day 8 - 12, the GDF-9 gene expression level of oocytes in vitro was significantly lower than that in vivo (P 〈 0.05). We conclude that M Ⅱ oocytes can be obtained from in vitro culture of preantral follicles. The GDF- 9 gene expression of oocytes varies at different growth stages in vivo. The low expression of GDF-9 in oocytes cuhured in vitro may be the cause of their low developmental capacity.展开更多
To investigate the effects of Radix pseudostellariae fibrous root extracts(RPFRE) on serum cytokines in normal and immunosuppressed mice and the correlation between indexes, KM male mice were randomly divided into fou...To investigate the effects of Radix pseudostellariae fibrous root extracts(RPFRE) on serum cytokines in normal and immunosuppressed mice and the correlation between indexes, KM male mice were randomly divided into four groups, which were given 0(control), 0.1, 0.2, 0.4 g/kg RPFRE by gavage. The levels of IL-2, IL-4, IL-6, and IFN-γ in the serum of mice were measured 14 d after gavage. On the 15day, the remaining mice in the experimental group were intraperitoneally injected with cyclophosphamide(CY), and samples were collected on the 18day to measure serum cytokines levels. The results showed that RPFRE improved the serum cytokine level in normal mice. 0.1 g/kg RPFRE significantly increased the content of IL-2and IFN-γ(P<0.05), while 0.4 g/kg RPFRE significantly increased the content of IL-4 and IL-6(P<0.05). Correlation analysis showed that serum cytokines IL-4 and IL-6 in normal mice had an extremely significant positive correlation with RPFRE concentration(P<0.01), IL-2 had a significant or extremely significant positive correlation with IL-4, IL-6, and IFN-γ(P<0.01or P<0.05), and IL-4 had an extremely significant positive correlation with IL-6(P<0.01). After CY injection, serum cytokine levels in mice decreased and immune function was inhibited. Compared with the control group, the experimental group recovered the level of cytokines to some extent. 0.1 g/kg RPFRE significantly increased the content of IL-2 in immunosuppressed mice(P<0.05), and 0.4 g/kg RPFRE significantly increased the content of IL-4, IL-6, and IFN-γ in immunosuppressed mice(P<0.05). Correlation analysis showed that the serum cytokines in immunosuppressed mice were significantly positively correlated with RPFRE concentration(P<0.01), and there was a certain dose dependence. Moreover, the correlation coefficient between IL-2 and IL-4, IL-6, and IFN-γ, IL-4 and IL-6, and IL-6 and IFN-γ reached an extremely significant level(P<0.01). To sum up, RPFRE could improve the serum cytokines level of mice, promote the secretion of cytokines, and have a certain immune protective effect. There was a significant positive correlation between the RPFRE concentration and the serum cytokines in mice, which provided basic data support for the further study of RPFRE immune function.展开更多
AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic b...AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.展开更多
AIM:To study the effect of salvianolate on expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA in small intestine of cirrhotic rats. METHODS:Cirrhosis in rats was induced using CCl4 (0.3 mL/kg). R...AIM:To study the effect of salvianolate on expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA in small intestine of cirrhotic rats. METHODS:Cirrhosis in rats was induced using CCl4 (0.3 mL/kg). Rats were randomly divided into non-treatment group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and treated for 2 wk. Another 10 healthy rats served as a normal control group. Mortality of cirrhotic rats in each group was evaluated after treatment with salvianolate. Serum samples were taken from portal vein for the detection of endotoxin. Morphological changes in tissue samples from the ileocecum were observed under a light microscope. Expression of TNF-α and IL-6 mRNA in the small intestine of rats was analyzed by real-time reverse-transcriptase polymerase chain reaction. RESULTS:The mortality of cirrhotic rats in the nontreatment group was 37.5%. No cirrhotic rat died in the high-dose salvianolate treatment group. The serum endotoxin level was significantly higher in the non-treatment group than in the salvianolate treatment and normal control groups. The intestinal mucosal and villous atrophy,necrosis and shedding of the intestinal mucosal epithelium,observed in the non-treatment group,were reversed in different salvianolate treatment groups. The TNF-α and IL-6 mRNA expression levels in small intestine were significantly lower in different salvianolate treatment groups than in the non-treatment group. CONCLUSION:Salvianolate can reduce the endotoxin level,ameliorate the injury of intestinal mucosa,and inhibit the expression of TNF-α and IL-6 mRNA in small intestine of cirrhotic rats.展开更多
AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously i...AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.展开更多
AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:M...AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:Male Wistar rats were randomly divided into three groups(36 rats each) :the sham-operation group(group S) ,lower limb ischemia-reperfusion group(group LIR) ,and penehyclidine hydrochloride postconditioning group(group PHC) .Each group was divided into subgroups(n=6 in each group) according to ischemic-reperfusion time,i.e.immediately 0 h(T1) ,1 h(T2) ,3 h(T3) ,6 h(T4) ,12 h(T5) ,and 24 h(T6) .Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h.In group PHC,0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia.The designated rats were sacrificed at different time-points of reperfusion;diamine oxidase(DAO) ,superoxide dismutase(SOD) activity,myeloperoxidase(MPO) of small intestinal tissue,plasma endotoxin,DAO,tumor necrosis factor-α(TNF-α) ,and interleukin(IL) -10 in serum were detected in the rats. RESULTS:The pathological changes in the small intestine were observed under light microscope.The levels of MPO,endotoxin,serum DAO,and IL-10 at T1-T6,and TNF-αlevel at T1-T4 increased in groups LIR and PHC(P<0.05) compared with those in group S,but tissue DAO and SOD activity at T1-T6 decreased(P<0.05) .In group PHC,the tissue DAO and SOD activity at T2-T6,and IL-10 at T2-T5 increased to higher levels than those in group LIR(P<0.05) ;however,the levels of MPO,endotoxin,and DAO in the blood at T2-T6,and TNF-αat T2 and T4 decreased(P<0.05) . CONCLUSION:Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR.Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.展开更多
AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, w...AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were ex- amined in wild-type mice and mice infected with Helico- bacter pylori (H. pylorO. Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ, alone, mice were given a subcutaneous infusion of IFNγ, for 7 d. Finally, the influ- ence of IFNγ, and somatostatin on the ghrelin promoter was characterized. RESULTS: H. py/ori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was in- versely correlated with gastric inflammation in achlorh- dyric mouse models. Subcutaneous infusion of IFNγ, suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of soma- tostatin but not under that of IFNγ. CONCLUSION: Gastric infection and inflammation is associated with increased IFNγ, expression and reduced ghrelin expression. IFNγ, does not directly control ghre- lin expression but inhibits it indirectly via somatostatin.展开更多
This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF)...This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).展开更多
OBJECTIVE: To assess the effectiveness of violateoil from Blumea Balsamifera(L.) DC. leaves(BB oil)on wound healing in mice.METHODS: Undiluted BB oil and its diluted solutions with olive oil to 1/5 and 1/10 to yield B...OBJECTIVE: To assess the effectiveness of violateoil from Blumea Balsamifera(L.) DC. leaves(BB oil)on wound healing in mice.METHODS: Undiluted BB oil and its diluted solutions with olive oil to 1/5 and 1/10 to yield BB oil1/5and BB oil1/10 were applied to the wounded skin before wound healing conditions were assessed by healing rate, histopathology, and contents of collagen, hydroxyproline, and Neuropeptide Substance P(SP). All above results were compared with the efficacies of the control, pure olive oil, basic fibroblast growth factor(BFGF), and cream of Jing Wan Hong(JWH).RESULTS: BB oil1/5and BB oil1/10 improved wound contraction and closure. Histopathology study further confirmed a desirable histological organization of wound tissues. BB oil1/5and BB oil1/10 reduced the number of inflammatory cells, increased wound-healing rates, and significantly increased the hydroxyproline content. Both BB oil1/5and BB oil1/10 improved formation of collagen, and reduced the frequency of fibroblasts. Moreover, BB oil1/5and BB oil1/10 markedly promoted SP expression. However, undiluted BB oil may induce skin thickening and hardening, inhibite collagen synthesis and delay complete skin wound healing.CONCLUSION: The BB oil1/5and BB oil1/10 promoted capillary regeneration, blood circulation, collagen deposition, granular tissue formation, epithelial deposition, and wound contraction. The mechanism underlying the action might be related to induction of SP secretion, and the proliferation and differentiation of mesenchymal cells.展开更多
The gut microbiota plays a key role in obesity and related metabolic disorders, and multiple factors including diet, host genotype, and age regulate it. Many studies have examined the contribution of extrinsic factors...The gut microbiota plays a key role in obesity and related metabolic disorders, and multiple factors including diet, host genotype, and age regulate it. Many studies have examined the contribution of extrinsic factors to the regulation of the gut microbiota, but the importance of the host genetic constitution cannot be ignored, lnterleukin 17A (lL-17A), a pro-inflammatory cytokine, is important in the defense against infection and diseases. Here, we investigated the association among IL-17, a high-fat diet (HFD), and the gut microbiota. Mice deficient in 1L-17A were resistant to diet-induced obesity and related diseases. Compared with the I1-17a^-/1 mice, wild-type (WT) mice challenged with HFD showed obvious weight fluctuations, such as those seen in type 2 diabetes, and hematological changes similar to those associated with metabolic syndrome. However, housing WT mice and Il-17a^-/- mice together signifi- cantly alleviated these symptoms in the WT mice. A metagenomic analysis of the mouse feces indicated that the microbial community compositions of these two groups differed before HFD feeding. The HFD mediated shifts in the gut microbial compositions, which were associated with the mouse phenotypes. We also identified potentially beneficial and harmful species present during this period, and drew net- works of the most abundant species. A functional analysis indicated pathway changes in the WT and I1-17a^- /- mice when fed the HFD. Collectively, these data underscore the importance of the host factor IL-17A in shaping and regulating the gut microbiota, which conversely, influences the host health.展开更多
文摘Mice preantral follicles were cultured in vitro for 12 days to achieve metaphase Ⅱ (M Ⅱ ) oocytes. Oocyte growth differentiation factor-9 (GDF-9) gene expression was measured during different growth stages to explore the relationship between oocyte maturation and GDF-9 gene expression. Preantral follicles of lO-day old mice were isolated from the ovaries and were cultured for 12 days. Oocytes from day 2 (D2), D4, D6, D8, DIO, D12 cultured in vitro were named the in vitro group and oocytes of day 12 (D12), D14, D16, D18, D20, D22 grown in vivo were named the in vivo group. Follicle survival, antrum formation and maturation rate were 89.5%, 51.8% and 56.6% respectively in follicles cultured in vitro. After RT-PCR and agarose gel electrophoresis, relative mRNA abundance of GDF-9 was measured in each group of oocytes. At day 8 - 12, the GDF-9 gene expression level of oocytes in vitro was significantly lower than that in vivo (P 〈 0.05). We conclude that M Ⅱ oocytes can be obtained from in vitro culture of preantral follicles. The GDF- 9 gene expression of oocytes varies at different growth stages in vivo. The low expression of GDF-9 in oocytes cuhured in vitro may be the cause of their low developmental capacity.
文摘0021889 应用可卡因和吸嚼烟草者与自发流产的危险性/Ness R B//New Eng J Med.-1999,340(5).-333~339 津医情0021890 促凝血的 fg12凝血酶原酶介导CBAx DBA/2小鼠细胞因子依赖的流产/Clark D A//J Immunol.-1998,160(2).-545~549 四军大0021891 孕期出血细菌性阴道病、常见生殖道感染,早产的危险与治疗好处/French J I//Obstet Gynecol.1999,93(5Part 1).-715~724 津医情0021892 前列腺素 E 受体的调节:感染诱导早产的可能机理/Spaziani E
文摘To investigate the effects of Radix pseudostellariae fibrous root extracts(RPFRE) on serum cytokines in normal and immunosuppressed mice and the correlation between indexes, KM male mice were randomly divided into four groups, which were given 0(control), 0.1, 0.2, 0.4 g/kg RPFRE by gavage. The levels of IL-2, IL-4, IL-6, and IFN-γ in the serum of mice were measured 14 d after gavage. On the 15day, the remaining mice in the experimental group were intraperitoneally injected with cyclophosphamide(CY), and samples were collected on the 18day to measure serum cytokines levels. The results showed that RPFRE improved the serum cytokine level in normal mice. 0.1 g/kg RPFRE significantly increased the content of IL-2and IFN-γ(P<0.05), while 0.4 g/kg RPFRE significantly increased the content of IL-4 and IL-6(P<0.05). Correlation analysis showed that serum cytokines IL-4 and IL-6 in normal mice had an extremely significant positive correlation with RPFRE concentration(P<0.01), IL-2 had a significant or extremely significant positive correlation with IL-4, IL-6, and IFN-γ(P<0.01or P<0.05), and IL-4 had an extremely significant positive correlation with IL-6(P<0.01). After CY injection, serum cytokine levels in mice decreased and immune function was inhibited. Compared with the control group, the experimental group recovered the level of cytokines to some extent. 0.1 g/kg RPFRE significantly increased the content of IL-2 in immunosuppressed mice(P<0.05), and 0.4 g/kg RPFRE significantly increased the content of IL-4, IL-6, and IFN-γ in immunosuppressed mice(P<0.05). Correlation analysis showed that the serum cytokines in immunosuppressed mice were significantly positively correlated with RPFRE concentration(P<0.01), and there was a certain dose dependence. Moreover, the correlation coefficient between IL-2 and IL-4, IL-6, and IFN-γ, IL-4 and IL-6, and IL-6 and IFN-γ reached an extremely significant level(P<0.01). To sum up, RPFRE could improve the serum cytokines level of mice, promote the secretion of cytokines, and have a certain immune protective effect. There was a significant positive correlation between the RPFRE concentration and the serum cytokines in mice, which provided basic data support for the further study of RPFRE immune function.
基金Supported by The Fundamental Research Funds for the Central Universities No.JKQ2011008,JKQ2011010Postdoctoral Science Foundation of Jiangsu Province,China,No.1101029C
文摘AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.
基金Supported by Natural Science Foundation of Zhejiang Medical College 2009XZB06
文摘AIM:To study the effect of salvianolate on expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA in small intestine of cirrhotic rats. METHODS:Cirrhosis in rats was induced using CCl4 (0.3 mL/kg). Rats were randomly divided into non-treatment group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and treated for 2 wk. Another 10 healthy rats served as a normal control group. Mortality of cirrhotic rats in each group was evaluated after treatment with salvianolate. Serum samples were taken from portal vein for the detection of endotoxin. Morphological changes in tissue samples from the ileocecum were observed under a light microscope. Expression of TNF-α and IL-6 mRNA in the small intestine of rats was analyzed by real-time reverse-transcriptase polymerase chain reaction. RESULTS:The mortality of cirrhotic rats in the nontreatment group was 37.5%. No cirrhotic rat died in the high-dose salvianolate treatment group. The serum endotoxin level was significantly higher in the non-treatment group than in the salvianolate treatment and normal control groups. The intestinal mucosal and villous atrophy,necrosis and shedding of the intestinal mucosal epithelium,observed in the non-treatment group,were reversed in different salvianolate treatment groups. The TNF-α and IL-6 mRNA expression levels in small intestine were significantly lower in different salvianolate treatment groups than in the non-treatment group. CONCLUSION:Salvianolate can reduce the endotoxin level,ameliorate the injury of intestinal mucosa,and inhibit the expression of TNF-α and IL-6 mRNA in small intestine of cirrhotic rats.
文摘AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.
基金Supported by Lanzhou City Development Plan of Science and Technology,No.2009-1-52
文摘AIM:To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion(LIR) injury. METHODS:Male Wistar rats were randomly divided into three groups(36 rats each) :the sham-operation group(group S) ,lower limb ischemia-reperfusion group(group LIR) ,and penehyclidine hydrochloride postconditioning group(group PHC) .Each group was divided into subgroups(n=6 in each group) according to ischemic-reperfusion time,i.e.immediately 0 h(T1) ,1 h(T2) ,3 h(T3) ,6 h(T4) ,12 h(T5) ,and 24 h(T6) .Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h.In group PHC,0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia.The designated rats were sacrificed at different time-points of reperfusion;diamine oxidase(DAO) ,superoxide dismutase(SOD) activity,myeloperoxidase(MPO) of small intestinal tissue,plasma endotoxin,DAO,tumor necrosis factor-α(TNF-α) ,and interleukin(IL) -10 in serum were detected in the rats. RESULTS:The pathological changes in the small intestine were observed under light microscope.The levels of MPO,endotoxin,serum DAO,and IL-10 at T1-T6,and TNF-αlevel at T1-T4 increased in groups LIR and PHC(P<0.05) compared with those in group S,but tissue DAO and SOD activity at T1-T6 decreased(P<0.05) .In group PHC,the tissue DAO and SOD activity at T2-T6,and IL-10 at T2-T5 increased to higher levels than those in group LIR(P<0.05) ;however,the levels of MPO,endotoxin,and DAO in the blood at T2-T6,and TNF-αat T2 and T4 decreased(P<0.05) . CONCLUSION:Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR.Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.
基金Supported by The Danish MRC Grant271-08-0378(LFH)the ALF grant(TW)The Lundbeck foundation(KBVD)
文摘AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were ex- amined in wild-type mice and mice infected with Helico- bacter pylori (H. pylorO. Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ, alone, mice were given a subcutaneous infusion of IFNγ, for 7 d. Finally, the influ- ence of IFNγ, and somatostatin on the ghrelin promoter was characterized. RESULTS: H. py/ori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was in- versely correlated with gastric inflammation in achlorh- dyric mouse models. Subcutaneous infusion of IFNγ, suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of soma- tostatin but not under that of IFNγ. CONCLUSION: Gastric infection and inflammation is associated with increased IFNγ, expression and reduced ghrelin expression. IFNγ, does not directly control ghre- lin expression but inhibits it indirectly via somatostatin.
基金supported in part by the Key Technologies Research and Development Program for Infectious Diseases of China (Grant No. 2012ZX10003001)the Key Project of Science and Technology of Shanghai (Grant No.10411955000)the Shanghai Science and Technology Development Funds (Grant No. 10XD1400900)
文摘This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).
基金the Fundamental Scientific Research Funds for Chinese Academy of Tropical Agricultural Sciences-Tropical Crops Genetic Resources Institute[The Evaluation and Mechanism Research for the Treatment of Ainaxiang(Herba Blumeae Balsamiferae)Oil on Skin Burns Based on Cytokines,No.#1630032014016]the Natural Science Fund of Hainan Province[the Evaluation and Mechanism Research of Ainaxiang(Herba Blumeae Balsamiferae)Oil on Healingand Repairing of Skin Wounds,No.#312022]the Natural Science Fund of China(Study on Variety Classification of"Nalong"and It's Ethanopharmacology of Li in Hainan,No.#81374065)
文摘OBJECTIVE: To assess the effectiveness of violateoil from Blumea Balsamifera(L.) DC. leaves(BB oil)on wound healing in mice.METHODS: Undiluted BB oil and its diluted solutions with olive oil to 1/5 and 1/10 to yield BB oil1/5and BB oil1/10 were applied to the wounded skin before wound healing conditions were assessed by healing rate, histopathology, and contents of collagen, hydroxyproline, and Neuropeptide Substance P(SP). All above results were compared with the efficacies of the control, pure olive oil, basic fibroblast growth factor(BFGF), and cream of Jing Wan Hong(JWH).RESULTS: BB oil1/5and BB oil1/10 improved wound contraction and closure. Histopathology study further confirmed a desirable histological organization of wound tissues. BB oil1/5and BB oil1/10 reduced the number of inflammatory cells, increased wound-healing rates, and significantly increased the hydroxyproline content. Both BB oil1/5and BB oil1/10 improved formation of collagen, and reduced the frequency of fibroblasts. Moreover, BB oil1/5and BB oil1/10 markedly promoted SP expression. However, undiluted BB oil may induce skin thickening and hardening, inhibite collagen synthesis and delay complete skin wound healing.CONCLUSION: The BB oil1/5and BB oil1/10 promoted capillary regeneration, blood circulation, collagen deposition, granular tissue formation, epithelial deposition, and wound contraction. The mechanism underlying the action might be related to induction of SP secretion, and the proliferation and differentiation of mesenchymal cells.
基金supported by the National High Technology Research and Development Program (2015AA020702)
文摘The gut microbiota plays a key role in obesity and related metabolic disorders, and multiple factors including diet, host genotype, and age regulate it. Many studies have examined the contribution of extrinsic factors to the regulation of the gut microbiota, but the importance of the host genetic constitution cannot be ignored, lnterleukin 17A (lL-17A), a pro-inflammatory cytokine, is important in the defense against infection and diseases. Here, we investigated the association among IL-17, a high-fat diet (HFD), and the gut microbiota. Mice deficient in 1L-17A were resistant to diet-induced obesity and related diseases. Compared with the I1-17a^-/1 mice, wild-type (WT) mice challenged with HFD showed obvious weight fluctuations, such as those seen in type 2 diabetes, and hematological changes similar to those associated with metabolic syndrome. However, housing WT mice and Il-17a^-/- mice together signifi- cantly alleviated these symptoms in the WT mice. A metagenomic analysis of the mouse feces indicated that the microbial community compositions of these two groups differed before HFD feeding. The HFD mediated shifts in the gut microbial compositions, which were associated with the mouse phenotypes. We also identified potentially beneficial and harmful species present during this period, and drew net- works of the most abundant species. A functional analysis indicated pathway changes in the WT and I1-17a^- /- mice when fed the HFD. Collectively, these data underscore the importance of the host factor IL-17A in shaping and regulating the gut microbiota, which conversely, influences the host health.