Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intra...Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intraperitoneal injection of streptozotocin.The 30 Wistar rats successfully modeled were randomly divided into a model group,a bone marrow mesenchymal stem cell group and a combined group(α1-antitrypsin combined with bone marrow Mesenchymal stem cells),the blood glucose and serum insulin levels of diabetic rats were measured 4 weeks after treatment.Enzyme-linked immunosorbent assay(ELISA)for measuring serum inflammatory factors IL-1β,IL-6 and TNF-α in rats.Observing the pathological morphology of rat retina under hematoxylin-eosin staining(HE).TUNEL staining to observe the apoptosis of rat retinal nerve cells.Immunohistochemical method to detect the expression level of CD45 in retinal tissue.Real-time fluorescence quantitative PCR was used to detect the expression of retinal vascular endothelial growth factor(VEGF),hypoxiainducible factor-1α(HIF-1α),and angiotensinⅡ(ANGⅡ)mRNA.Western blot was used to detect the expression of p38 MAPK/NF-κB signaling pathway-related proteins in the retinal tissue of each group of rats.Results:Compared with the control group,the rats in the model group had increased blood glucose,decreased insulin levels,increased serum IL-1β,IL-6,and TNF-α levels,and had obvious lesions in the retina.CD45 showed high expression in retinal tissue,VEGF,HIF-1α,ANGⅡ mRNA expression increased,p-p38,p-p65,p-IκBα protein expression increased(P<0.05).Compared with the model group,the bone marrow mesenchymal stem cell group and the combined group have decreased blood glucose,increased insulin levels,and decreased serum IL-1β,IL-6 and TNF-α levels.Retinopathy is improved,apoptosis of retinal nerve cells is reduced,CD45 expression in retinal tissue is reduced,VEGF,HIF-1α,ANGⅡ mRNA expression is decreased,and p-p38,p-p65,p-IκBα protein expression is decreased.Compared with the bone marrow mesenchymal stem cell group,the effect of the combined group was more obvious(P<0.05).Conclusion:α1-antitrypsin combined with bone marrow mesenchymal stem cell transplantation can improve the degree of retinopathy in diabetic rats.The mechanism may be related to the inhibition of p38 MAPK/NF-κB signaling pathway.展开更多
Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with gr...Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.展开更多
基金Key Rearch and Development projects in Shaanxi Province(2019SF-084).
文摘Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intraperitoneal injection of streptozotocin.The 30 Wistar rats successfully modeled were randomly divided into a model group,a bone marrow mesenchymal stem cell group and a combined group(α1-antitrypsin combined with bone marrow Mesenchymal stem cells),the blood glucose and serum insulin levels of diabetic rats were measured 4 weeks after treatment.Enzyme-linked immunosorbent assay(ELISA)for measuring serum inflammatory factors IL-1β,IL-6 and TNF-α in rats.Observing the pathological morphology of rat retina under hematoxylin-eosin staining(HE).TUNEL staining to observe the apoptosis of rat retinal nerve cells.Immunohistochemical method to detect the expression level of CD45 in retinal tissue.Real-time fluorescence quantitative PCR was used to detect the expression of retinal vascular endothelial growth factor(VEGF),hypoxiainducible factor-1α(HIF-1α),and angiotensinⅡ(ANGⅡ)mRNA.Western blot was used to detect the expression of p38 MAPK/NF-κB signaling pathway-related proteins in the retinal tissue of each group of rats.Results:Compared with the control group,the rats in the model group had increased blood glucose,decreased insulin levels,increased serum IL-1β,IL-6,and TNF-α levels,and had obvious lesions in the retina.CD45 showed high expression in retinal tissue,VEGF,HIF-1α,ANGⅡ mRNA expression increased,p-p38,p-p65,p-IκBα protein expression increased(P<0.05).Compared with the model group,the bone marrow mesenchymal stem cell group and the combined group have decreased blood glucose,increased insulin levels,and decreased serum IL-1β,IL-6 and TNF-α levels.Retinopathy is improved,apoptosis of retinal nerve cells is reduced,CD45 expression in retinal tissue is reduced,VEGF,HIF-1α,ANGⅡ mRNA expression is decreased,and p-p38,p-p65,p-IκBα protein expression is decreased.Compared with the bone marrow mesenchymal stem cell group,the effect of the combined group was more obvious(P<0.05).Conclusion:α1-antitrypsin combined with bone marrow mesenchymal stem cell transplantation can improve the degree of retinopathy in diabetic rats.The mechanism may be related to the inhibition of p38 MAPK/NF-κB signaling pathway.
文摘Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.
