Summary: To study the efficacy and the mechanism of Colquhoumia root ( Tripterygium hypoglaucure (Le,vL) Hutch) in the treatment of mesangial proliferation glomerulonephritis (MsPGN), SD rats were injected with...Summary: To study the efficacy and the mechanism of Colquhoumia root ( Tripterygium hypoglaucure (Le,vL) Hutch) in the treatment of mesangial proliferation glomerulonephritis (MsPGN), SD rats were injected with anti-thymoeyte serum (ATS) to make MsPGN model (anti-Thyl model). The rats were then divided into 3 groups: normal control group, anti-Thyl model group and treatment group. Histopathologieal (HE, PAS), immunohistoehemieal, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β protein and mRNA in the tissues of kidney. Our result showed that proteinuria and the ratio of extraeellular matrix/glomerular capillaries area (ECM/CA) were increased significantly in model group. The expression of both TGF-β protein and mRNA in glomeruli was much higher in model group than in control group (P〈0.01). After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.展开更多
Inflammatory cells infiltrated in glomeruli and proliferating glomerular cells were immunohistochemically studied in 87 renal biopsies from patients withglomerulonephritides(GN) of various types, by using monoclonal a...Inflammatory cells infiltrated in glomeruli and proliferating glomerular cells were immunohistochemically studied in 87 renal biopsies from patients withglomerulonephritides(GN) of various types, by using monoclonal antibody toMac387 and PCNA(proliferative cell nuclear antigen) respectively. The resultsshowed that the expressions of Mac387 and PCNA were generally increased inproliferative GN , compared with non-proliferative GN. The expression of Mac387was related to the severity of mesangial cell proliferation determined by light microscopy, but the increase of PCNA expression was found in severely proliferativeGN. Although certain relationship between Mac387 and PCNA expression onglomerular cells was observed. it was not statistically significant. Finally, thepossible mechanism of glomerular mesangial proliferation was discussed.展开更多
Objective:To investigate the effects of emodin(EMD) on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods:The effects of EMD on cell proliferation and IL-6, TGF-β1 sec...Objective:To investigate the effects of emodin(EMD) on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods:The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. Cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results:EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats (P 〈 0.05). Conclusion:EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix(ECM), this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.展开更多
Objective To elucidate the renoprotective effect of resveratrol(RSV)on sphingosine kinase 1(SphK1)signaling pathway and expression of its downstream molecules including activator protein 1(AP-1)and transformation grow...Objective To elucidate the renoprotective effect of resveratrol(RSV)on sphingosine kinase 1(SphK1)signaling pathway and expression of its downstream molecules including activator protein 1(AP-1)and transformation growth factor-β1(TGF-β1)in lipopolysaccharide(LPS)-induced glomerular mesangial cells(GMCs).Methods The rat GMCs line(HBZY-1)were cultured and randomly divided into 5 groups,including control,LPS(100 ng/mL),and 5,10,20µmol/L RSV-treated groups.In addition,SphK1 inhibitor(SK-II)was used as positive control.GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h.GMCs proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The proteins expression of SphK1,p-c-Jun and TGF-β1 in GMCs were detected by Western blot,and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay(EMSA).The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.Results LPS could obviously stimulate GMCs proliferation,elevate SphK1,p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1(P<0.05 or P<0.01),whereas these effects were significantly blocked by RSV pretreatment.It was also suggested that the effect of RSV was similar to SK-II(P>0.05).Moreover,RSV exhibited good binding affinity towards SphK1,with docking scores of−8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.Conclusion RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression,which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.展开更多
Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC prol...Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and activation of NF-KB of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively.Results Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide ( LPS )-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-KB. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture.Conclusion Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-KB activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive reanl diseases aside from its lipid-lowering effect.展开更多
文摘Summary: To study the efficacy and the mechanism of Colquhoumia root ( Tripterygium hypoglaucure (Le,vL) Hutch) in the treatment of mesangial proliferation glomerulonephritis (MsPGN), SD rats were injected with anti-thymoeyte serum (ATS) to make MsPGN model (anti-Thyl model). The rats were then divided into 3 groups: normal control group, anti-Thyl model group and treatment group. Histopathologieal (HE, PAS), immunohistoehemieal, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β protein and mRNA in the tissues of kidney. Our result showed that proteinuria and the ratio of extraeellular matrix/glomerular capillaries area (ECM/CA) were increased significantly in model group. The expression of both TGF-β protein and mRNA in glomeruli was much higher in model group than in control group (P〈0.01). After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.
文摘Inflammatory cells infiltrated in glomeruli and proliferating glomerular cells were immunohistochemically studied in 87 renal biopsies from patients withglomerulonephritides(GN) of various types, by using monoclonal antibody toMac387 and PCNA(proliferative cell nuclear antigen) respectively. The resultsshowed that the expressions of Mac387 and PCNA were generally increased inproliferative GN , compared with non-proliferative GN. The expression of Mac387was related to the severity of mesangial cell proliferation determined by light microscopy, but the increase of PCNA expression was found in severely proliferativeGN. Although certain relationship between Mac387 and PCNA expression onglomerular cells was observed. it was not statistically significant. Finally, thepossible mechanism of glomerular mesangial proliferation was discussed.
文摘Objective:To investigate the effects of emodin(EMD) on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods:The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. Cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results:EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats (P 〈 0.05). Conclusion:EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix(ECM), this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.
基金Supported by the National Natural Science Foundation of China(No.81603355,81900745)。
文摘Objective To elucidate the renoprotective effect of resveratrol(RSV)on sphingosine kinase 1(SphK1)signaling pathway and expression of its downstream molecules including activator protein 1(AP-1)and transformation growth factor-β1(TGF-β1)in lipopolysaccharide(LPS)-induced glomerular mesangial cells(GMCs).Methods The rat GMCs line(HBZY-1)were cultured and randomly divided into 5 groups,including control,LPS(100 ng/mL),and 5,10,20µmol/L RSV-treated groups.In addition,SphK1 inhibitor(SK-II)was used as positive control.GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h.GMCs proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The proteins expression of SphK1,p-c-Jun and TGF-β1 in GMCs were detected by Western blot,and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay(EMSA).The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.Results LPS could obviously stimulate GMCs proliferation,elevate SphK1,p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1(P<0.05 or P<0.01),whereas these effects were significantly blocked by RSV pretreatment.It was also suggested that the effect of RSV was similar to SK-II(P>0.05).Moreover,RSV exhibited good binding affinity towards SphK1,with docking scores of−8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.Conclusion RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression,which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.
基金This work was supported by the National Education Foundation of China (No. 1999002309).
文摘Objective To study the effects and mechanism of lovastatin on cell proliferation and expression of proinflammatory cytokines in cultured human glomerular mesangial cells.Methods The influence of lovastatin on HMC proliferation was evaluated with 3H-thymidine incorporation. mRNA expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, and MCP-1) and activation of NF-KB of HMC were measured using Reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA) respectively.Results Lovastatin was found to have inhibitory effects on human mesangial cell (HMC) proliferation and lipopolysaccharide ( LPS )-mediated human mesangine cell HMC mRNA expression of proinflammatory cytokines via activation of NF-KB. The effect of lovstatin on HMC could be prevented when the mevalonate and farnesol were added to the culture.Conclusion Lovastatin may decrease HMC proliferation and production of proinflammatory cytokines through the inhibition of NF-KB activation. This provided experimental evidence for further evaluation of the renal protective effect of HRI, suggesting that it may be a potent agent for prevention of progressive reanl diseases aside from its lipid-lowering effect.