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目的细粒棘球蚴感染存在自发性免疫调节现象,在人体内经历了从Th1向Th2的极化过程。文中探讨细粒棘球蚴抗原B对小鼠实验性自身免疫性1型糖尿病的保护作用及其机制。方法采用随机数字表法将30只雄BALB/c小鼠随机分为3组:肌内注射细粒棘球蚴抗原B+糖尿病成模组(实验组,n=10);肌注等渗盐水+糖尿病成模组(等渗盐水对照组,n=10);糖尿病成模组(阳性对照组,n=10);实验组、等渗盐水对照组、阳性对照组均给予小剂量链脲佐菌素(STZ)诱导1型糖尿病,动态观察血糖变化。至3周末留取小鼠血清后,取胰腺组织切片HE染色,进行胰岛功能评价,免疫组化染色,观察胰岛β细胞总量变化,用ELISA测定血清白介素-2(interleukin-2,IL-2)、IL-10水平,间接放射免法测定血清胰岛素。结果给药后,小鼠血糖逐渐升高,在第3天和成模后1周、2周、3周,等渗盐水对照组[(21.91±3.11)、(24.77±4.29)、(32.47±2.03)、(18.13±2.18)mmol/L]和阳性对照组[(22.63±3.55)、(22.89±5.69)、(29.37±3.37)、(29.57±5.37)mmol/L]血糖水平分别显著高于实验组[(16.19±4.58)、(18.82±2.15)、(21.66±1.63)、(20.76±2.29)mmol/L],差异有统计学意义(P<0.05);实验组胰岛可见淋巴细胞浸润不多,而等渗盐水对照组和阳性对照组胰岛可见较多淋巴细胞浸润;在模型建立3周后,实验组小鼠血清胰岛素水平[(35.10±3.86)mIU/L]高于等渗盐水对照组[(27.16±6.11)mIU/L]和阳性对照组[(25.13±4.16)mIU/L],差异有统计学意义(P<0.05),且实验组小鼠胰岛β细胞总量[(0.62±0.08)mg]高于等渗盐水对照组[(0.27±0.04)mg]和阳性对照组[(0.25±0.02)mg],差异有统计学意义(P<0.05);糖尿病模型建立3周末,实验组小鼠血清IL-10水平[(80.91±11.28)ng/mL]高于等渗盐水对照组[(32.70±6.57)ng/mL]和阳性对照组[(34.32±4.01)ng/mL],差异有统计学意义(P<0.05),实验组小鼠血清IL-2水平[(196.16±11.71)ng/mL]低于等渗盐水对照组[(267.30±69.28)ng/mL]和阳性对照组[(270.27±33.39)ng/mL],差异有统计学意义(P<0.05)。结论细粒棘球蚴抗原B对小鼠实验性1型糖尿病具有拮抗和保护作用,其机制可能与Th1/Th2免疫偏移有关。
Objective Echinococcus granulosus infection exists spontaneous immune regulatory phenomenon in the human body has experienced from Th1 to Th2 polarization process. In this paper, we explored the protective effect of Echinococcus granulosus antigen B on experimental autoimmune type 1 diabetes in mice and its mechanism. Methods Thirty male BALB / c mice were randomly divided into three groups: intramuscular injection of Echinococcus granulosus antigen B + diabetes mellitus (experimental group, n = 10); intramuscular isotonic saline + diabetes (N = 10); diabetic model group (n = 10); experimental group, isotonic saline control group and positive control group were given low-dose streptozotocin (STZ) induced type 1 diabetes mellitus, dynamic observation of blood glucose changes. The serum of mice was collected at the end of 3 weeks, then the pancreatic tissue sections were stained with hematoxylin and eosin (HE) for pancreatic islet function, immunohistochemical staining to observe the change of total islet β cell mass, and the levels of interleukin-2 (IL-2) ), IL-10 levels, indirect radioimmunoassay serum insulin. Results After administration, blood glucose of mice gradually increased. On the 3rd day and one week, 2 weeks and 3 weeks after modeling, the rats in the isotonic saline group [(21.91 ± 3.11), (24.77 ± 4.29), (32.47 ± 2.03), (18.13 ± 2.18) mmol / L] and positive control group [(22.63 ± 3.55), (22.89 ± 5.69), (29.37 ± 3.37), (29.57 ± 5.37) mmol / L] There were significant differences between the experimental group [(16.19 ± 4.58), (18.82 ± 2.15), (21.66 ± 1.63) and (20.76 ± 2.29) mmol / L, respectively , And more isotonic saline control group and positive control group islet more islet lymphocytes infiltration; 3 weeks after model establishment, the experimental group, serum insulin levels of mice [(35.10 ± 3.86) mIU / L] higher than the isotonic saline control (27.16 ± 6.11) mIU / L] and positive control group (25.13 ± 4.16) mIU / L], the difference was statistically significant (P <0.05) ± 0.08) mg] higher than those in the isotonic saline group (0.27 ± 0.04) mg and the positive control group (0.25 ± 0.02) mg, respectively (P <0.05) The level of serum IL-10 in experimental group [(80.91 ± 11.28) ng / mL] was higher than that in isotonic saline group [( (P <0.05). The level of IL-2 in the experimental group [(196.16 ± 11.71) ng · mL-1.70 ± 6.57 ng / mL] and the positive control group (34.32 ± 4.01 ng / mL) were significantly different / mL] was lower than that in the isotonic saline control group [(267.30 ± 69.28) ng / mL] and the positive control group (270.27 ± 33.39 ng / mL), the difference was statistically significant (P <0.05). Conclusion Echinococcus granulosus antigen B has antagonistic and protective effects on experimental type 1 diabetes mellitus in mice and its mechanism may be related to Th1 / Th2 immune offset.