Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lympho...Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.展开更多
The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown...The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.展开更多
Objective: To investigate the correlation between the gastric mucosal cell proliferation and low-concentration alcohol intake in a chronic drinking rat model, and to investigate the possible role of ROS/BMK1 pathway i...Objective: To investigate the correlation between the gastric mucosal cell proliferation and low-concentration alcohol intake in a chronic drinking rat model, and to investigate the possible role of ROS/BMK1 pathway in this process. Methods: SD rats were randomly divided into 4 groups: control group, administered with tap water; ethanol group, with 6% ethanol in the drinking water; quercetin group, with quercetin (100 mg/kg) by intragastric gavage twice a day; ethanol+quercetin group, administered with quercetin combined with 6% ethanol. The cell proliferation in rat gastric mucosa was analyzed by flow cytometery and proliferating cell nuclear antigen (PCNA) immunohistochemical staining. Activation of ERKs and BMK1 was evaluated by the expression and phosphorylation of these kinases using Western Blot analysis. Results: Compared to the controls, the cell proliferation in gastric mucosa of rats exposed to the ethanol for 7 d was enhanced, and the activation of BMK1 was also increased in this period. Otherwise quercetin, as a free radical scavenger, attenuated increased cell proliferation and activation of BMK1 in rat stomach treated with ethanol. However, no changes of ERKs expression and phosphorylation occurred in the rats in all groups. Conclusion: These results suggested that the ROS and BMK1 activation may be a central mechanism, which underlies cell proliferation in rat gastric mucosa stimulus with the chronic low-concentration ethanol.展开更多
文摘Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.
基金We are grateful to Dr Guan KL （Moore＇s Cancer Center, La Jolla, CA, USA） for the gift of pCMV-MEKca. This study was supported by the National Natural Science Foundation of China （30770787 and 90919035）, the National Basic Research Program of China （2005CB523301）, and the International Cooperation in Science and Technology Projects （2006DFB32460） and the Hebei Province Natural Science Foundation （C2007000831）.
文摘The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.
文摘Objective: To investigate the correlation between the gastric mucosal cell proliferation and low-concentration alcohol intake in a chronic drinking rat model, and to investigate the possible role of ROS/BMK1 pathway in this process. Methods: SD rats were randomly divided into 4 groups: control group, administered with tap water; ethanol group, with 6% ethanol in the drinking water; quercetin group, with quercetin (100 mg/kg) by intragastric gavage twice a day; ethanol+quercetin group, administered with quercetin combined with 6% ethanol. The cell proliferation in rat gastric mucosa was analyzed by flow cytometery and proliferating cell nuclear antigen (PCNA) immunohistochemical staining. Activation of ERKs and BMK1 was evaluated by the expression and phosphorylation of these kinases using Western Blot analysis. Results: Compared to the controls, the cell proliferation in gastric mucosa of rats exposed to the ethanol for 7 d was enhanced, and the activation of BMK1 was also increased in this period. Otherwise quercetin, as a free radical scavenger, attenuated increased cell proliferation and activation of BMK1 in rat stomach treated with ethanol. However, no changes of ERKs expression and phosphorylation occurred in the rats in all groups. Conclusion: These results suggested that the ROS and BMK1 activation may be a central mechanism, which underlies cell proliferation in rat gastric mucosa stimulus with the chronic low-concentration ethanol.
