The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mi...The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mice received, ad libitum, by oral route, the diet consisting of an aqueous extract (20 mg/mL) of the following flours: babassu mesocarp, manioc, corn or rice, during 120 days. The diet intake was monitored throughout this period. At the end, the weight variation, blood glucose, serum IgG and IgM antibody and IgM anti-insulin titers, were determined. The babassu and manioc flour extracts altered Purina chow intake and these animals also presented a significant increase in body weight. In contrast, treatment with rice flour resulted in a significant weight loss. Moderate to severe hyperglycemia was observed in the groups receiving rice and manioc, whereas treatment with babassu mesocarp flour and cornmeal resulted in hypoglycemia. The extracts did not alter the IgG concentration. On the other hand, the cornmeal extract caused a marked reduction in both total IgM and anti-insulin IgM antibody production. Although babassu mesocarp flour, cornmeal and manioc flour caused important variations in the parameters studied, only treatment with the rice flour extract anticipated the onset of diabetes in male mice genetically predisposed to the disease.展开更多
Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly rel...Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly relevant.We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and their ability to suppress diabetes transfer by diabeto- genic effector cells in secondary NOD-SCID recipients.Our data showed that the surface expressions of MHCⅡand CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice.The dendritic cells with a mature phenotype and increased MLR stimulation adop- tively transferred immune tolerogenic effects on secondary NOD-SCID mice,which were associated with significantly greater IL-10,TGF-beta production and CD4^+ CD25^+ T differentiation from splenocytes compared with NOD-SCID control recipients.Moreover,treatment with DC remarkably decreased the incidence of diabetes in secondary recipients.These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection against diabetes through polarizing the immune response towards a Th2 regulatory pathway.展开更多
Background Sjogren syndrome （SS） is an autoimmune disorder characterized by chronic lymphocytic infiltration and decreased secretion in salivary glands. Apoptosis is one of the possible mechanisms involved in acinar...Background Sjogren syndrome （SS） is an autoimmune disorder characterized by chronic lymphocytic infiltration and decreased secretion in salivary glands. Apoptosis is one of the possible mechanisms involved in acinar epithelial destruction in SS. The role of apoptosis in the initiation and effect phase of sialoadenitis is still controversial. The aim of this study was to observe the roles of apoptosis-associated proteins and serum IgG levels in sialoadenitis progression in nonobese diabetic （NOD） mice. Methods 2-, 5-, 10-, 15-, 20-week female NOD and matched BALB/c control mice were selected. Saliva and tear flow rate were measured. Serum IgG level was tested by enzyme-linked immunosorbent assay （ELISA）. Number of lymphocyte foci （NLF） in submandibular glands （SMGs） was counted under routine hematoxylin/eosin-stained sections. Expression of Fas, Bcl-2 and procaspase3 proteins as well as apoptotic cells in the SMGs were detected by immunohistochemical staining and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay respectively. Results Decreased stimulated total flow rate （STFR） and lymphocyte foci in SMGs were first observed in the 10-week NOD group. STFR was negatively correlated with NLF （P〈0.05）. Serum IgG in NOD mice was significantly higher than that of the control group （P〈0.05） and showed a positive correlation with NLF （P〈0.05）. Fas expression in SMGs acinar cells in NOD mice increased with age and was significantly higher compared with that in the control group. Bcl-2 expression and procaspase3 expression in SMG acinar cells in each NOD group were lower compared with those of the age-matched control mice. Conclusion Abnormal expression of Fas and Bcl-2 in the SMGs and higher level of serum IgG may contribute to the initiation of sialoadenitis and cause the glandular destruction in NOD mice.展开更多
目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾...目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T和CD4^+CD25^+Foxp3^+T细胞的频率,并采用3H-Td R掺入法检测脾CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能。结果人源化NOD小鼠和NOD小鼠的脾淋巴细胞和胰腺淋巴结细胞中CD4^+CD25^+Foxp3^+T细胞频率无显著性差异(P>0.05),而人源化NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T细胞等CD8^+Tregs亚群的频率较NOD小鼠都显著降低,但NOD小鼠人源化后,CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能并没有显著性差异;同时与人源化NOD小鼠相比,NOD小鼠的胰腺淋巴结细胞中CD8^+T细胞频率更低。结论人源化NOD小鼠脾脏和胰腺淋巴结中CD8^+Tregs亚群频率的降低,引起其胰腺淋巴结中CD8^+T细胞频率的升高,导致胰岛β细胞破坏更严重,可能是引起人源化NOD小鼠自发1型糖尿病较NOD小鼠明显提前且加重的因素之一。展开更多
目的 研究不同剂量壳寡糖对自发性糖尿病NOD小鼠糖代谢异常发生、发展过程的影响。方法每日灌胃低、中、高剂量壳寡糖(COS),定期观测各组NOD小鼠一般状态、体质量、摄食量、饮水量、空腹血糖(FBG)、餐后血糖(2 h PG)、口服糖耐量等,评...目的 研究不同剂量壳寡糖对自发性糖尿病NOD小鼠糖代谢异常发生、发展过程的影响。方法每日灌胃低、中、高剂量壳寡糖(COS),定期观测各组NOD小鼠一般状态、体质量、摄食量、饮水量、空腹血糖(FBG)、餐后血糖(2 h PG)、口服糖耐量等,评价各组小鼠自发性糖尿病发展进程,并比较各组小鼠肝糖原和肌糖原含量差异。结果各剂量壳寡糖可有效控制NOD小鼠每日摄食量和饮水量,在试验前半期显著抑制小鼠体质量增加,但后半期该抑制作用逐渐消失;可降低NOD小鼠FBG和2 h PG,改善口服糖耐量;可延后小鼠进入糖尿病前期和糖尿病阶段的时间,且壳寡糖低、中、高剂量组使小鼠处于糖尿病前期的时间段(对照组为9 w)分别延长为10 w、13 w和>16 w;各剂量壳寡糖可显著提高肝糖原和肌糖原含量(P<0.01),其中高剂量壳寡糖可使其分别提升405.9%和220.6%。结论壳寡糖可通过促进糖原合成改善NOD小鼠的糖尿病症状,延缓其进入糖尿病前期和糖尿病阶段,延长其处于糖尿病前期的时间,对自发性糖尿病的发生发展具有一定的阻滞作用。展开更多
文摘The aim of this study was to evaluate the effect of chronic treatment with diets rich in carbohydrates on the IgM and IgG antibody production and the seric glucose concentration in diabetes. Nonobese diabetic (NOD) mice received, ad libitum, by oral route, the diet consisting of an aqueous extract (20 mg/mL) of the following flours: babassu mesocarp, manioc, corn or rice, during 120 days. The diet intake was monitored throughout this period. At the end, the weight variation, blood glucose, serum IgG and IgM antibody and IgM anti-insulin titers, were determined. The babassu and manioc flour extracts altered Purina chow intake and these animals also presented a significant increase in body weight. In contrast, treatment with rice flour resulted in a significant weight loss. Moderate to severe hyperglycemia was observed in the groups receiving rice and manioc, whereas treatment with babassu mesocarp flour and cornmeal resulted in hypoglycemia. The extracts did not alter the IgG concentration. On the other hand, the cornmeal extract caused a marked reduction in both total IgM and anti-insulin IgM antibody production. Although babassu mesocarp flour, cornmeal and manioc flour caused important variations in the parameters studied, only treatment with the rice flour extract anticipated the onset of diabetes in male mice genetically predisposed to the disease.
基金This study was supported by the National Natural Science Foundation of China(No.30200343).
文摘Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells(DC)for the induction of peripheral toler- ance may be highly relevant.We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and their ability to suppress diabetes transfer by diabeto- genic effector cells in secondary NOD-SCID recipients.Our data showed that the surface expressions of MHCⅡand CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice.The dendritic cells with a mature phenotype and increased MLR stimulation adop- tively transferred immune tolerogenic effects on secondary NOD-SCID mice,which were associated with significantly greater IL-10,TGF-beta production and CD4^+ CD25^+ T differentiation from splenocytes compared with NOD-SCID control recipients.Moreover,treatment with DC remarkably decreased the incidence of diabetes in secondary recipients.These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection against diabetes through polarizing the immune response towards a Th2 regulatory pathway.
文摘Background Sjogren syndrome （SS） is an autoimmune disorder characterized by chronic lymphocytic infiltration and decreased secretion in salivary glands. Apoptosis is one of the possible mechanisms involved in acinar epithelial destruction in SS. The role of apoptosis in the initiation and effect phase of sialoadenitis is still controversial. The aim of this study was to observe the roles of apoptosis-associated proteins and serum IgG levels in sialoadenitis progression in nonobese diabetic （NOD） mice. Methods 2-, 5-, 10-, 15-, 20-week female NOD and matched BALB/c control mice were selected. Saliva and tear flow rate were measured. Serum IgG level was tested by enzyme-linked immunosorbent assay （ELISA）. Number of lymphocyte foci （NLF） in submandibular glands （SMGs） was counted under routine hematoxylin/eosin-stained sections. Expression of Fas, Bcl-2 and procaspase3 proteins as well as apoptotic cells in the SMGs were detected by immunohistochemical staining and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay respectively. Results Decreased stimulated total flow rate （STFR） and lymphocyte foci in SMGs were first observed in the 10-week NOD group. STFR was negatively correlated with NLF （P〈0.05）. Serum IgG in NOD mice was significantly higher than that of the control group （P〈0.05） and showed a positive correlation with NLF （P〈0.05）. Fas expression in SMGs acinar cells in NOD mice increased with age and was significantly higher compared with that in the control group. Bcl-2 expression and procaspase3 expression in SMG acinar cells in each NOD group were lower compared with those of the age-matched control mice. Conclusion Abnormal expression of Fas and Bcl-2 in the SMGs and higher level of serum IgG may contribute to the initiation of sialoadenitis and cause the glandular destruction in NOD mice.
文摘目的观察NOD小鼠人源化后,CD4^+和CD8^+调节性T细胞(regulatory T cells,Tregs)频率和功能的变化,揭示Tregs在人源化NOD小鼠1型糖尿病中的作用及免疫学机制可能的变化。方法流式细胞术分别分析12周龄未发病的人源化NOD小鼠和NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T和CD4^+CD25^+Foxp3^+T细胞的频率,并采用3H-Td R掺入法检测脾CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能。结果人源化NOD小鼠和NOD小鼠的脾淋巴细胞和胰腺淋巴结细胞中CD4^+CD25^+Foxp3^+T细胞频率无显著性差异(P>0.05),而人源化NOD小鼠脾淋巴细胞和胰腺淋巴结细胞中CD8^+CD122^+T、CD8^+CD28-T、CD8^+CD25^+Foxp3^+T细胞等CD8^+Tregs亚群的频率较NOD小鼠都显著降低,但NOD小鼠人源化后,CD4^+CD25^+T和CD8^+CD25^+T细胞的免疫抑制功能并没有显著性差异;同时与人源化NOD小鼠相比,NOD小鼠的胰腺淋巴结细胞中CD8^+T细胞频率更低。结论人源化NOD小鼠脾脏和胰腺淋巴结中CD8^+Tregs亚群频率的降低,引起其胰腺淋巴结中CD8^+T细胞频率的升高,导致胰岛β细胞破坏更严重,可能是引起人源化NOD小鼠自发1型糖尿病较NOD小鼠明显提前且加重的因素之一。
文摘目的 研究不同剂量壳寡糖对自发性糖尿病NOD小鼠糖代谢异常发生、发展过程的影响。方法每日灌胃低、中、高剂量壳寡糖(COS),定期观测各组NOD小鼠一般状态、体质量、摄食量、饮水量、空腹血糖(FBG)、餐后血糖(2 h PG)、口服糖耐量等,评价各组小鼠自发性糖尿病发展进程,并比较各组小鼠肝糖原和肌糖原含量差异。结果各剂量壳寡糖可有效控制NOD小鼠每日摄食量和饮水量,在试验前半期显著抑制小鼠体质量增加,但后半期该抑制作用逐渐消失;可降低NOD小鼠FBG和2 h PG,改善口服糖耐量;可延后小鼠进入糖尿病前期和糖尿病阶段的时间,且壳寡糖低、中、高剂量组使小鼠处于糖尿病前期的时间段(对照组为9 w)分别延长为10 w、13 w和>16 w;各剂量壳寡糖可显著提高肝糖原和肌糖原含量(P<0.01),其中高剂量壳寡糖可使其分别提升405.9%和220.6%。结论壳寡糖可通过促进糖原合成改善NOD小鼠的糖尿病症状,延缓其进入糖尿病前期和糖尿病阶段,延长其处于糖尿病前期的时间,对自发性糖尿病的发生发展具有一定的阻滞作用。
