白细胞介素1在介导人胰岛淀粉样多肽对 胰岛细胞毒性中的作用及机制. (Chinese)

Objective To explore the role of interleukin-1 (IL-1) in human islet amyloid polypeptide (iAPP) related pancreatic islet cell toxicity. Methods Pancreatic islets were isolated from adult Wistar rats and the cell vitality was identified. The islets were divided into control islets (group A), 10 μmol/L iAPP incubated islets (group B), 10 μmol/L iAPP plus 10 mg/L IL-1 receptor blocker (IL-1Ra) co-incubated islets (group C) and incubated for 24 h. Annexin-V/propidium iodide (PI) double-staining was used to detect islet cell apoptosis. The expressions of inflammation-related and apoptosis-related genes Bax Bcl-2 mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Independent sample t test was used for comparison between two groups. LSD test was used to compare the differences among three groups. Results (1) The apoptosis ratio and apoptosis-related gene expression: the apoptosis ratio in group B increased significantly than those in group A [(16.8±4.7) % vs (1.2±0.4) %]; while the apoptosis ratio in group C[(4.4 ± 2.1) % ] was significantly lower than those in group B (t=5.72, 4.17, respectively, both P<0.05). Consistently, the expression of Bax mRNA increased (2.28±0.46) times and Bcl-2 mRNA decreased (0.42±0.18) times in group B than those in group A (t=4.27, 3.10, respectively, both P<0.05). The expression of Bax mRNA decreased (0.48±0.17) times and the expression of Bcl-2 mRNA increased (1.93±0.25) times in group C than those in group B, respectively (t=3.41, 3.23,respectively, both P<0.05). (2) The expressions of the inflammatory factors: the expressions of IL-1β and tumor necrosis factor increased by (4.25±1.64) times and (3.19±1.04) times in group B than those in group A, respectively (t=3.39, 3.49, respectively, both P<0.05); While they decreased by (0.32±0.11) times and (0.28±0.11) times in group C than those in group B, respectively (t=2.94, 3.65, respectively, both P<0.05). Conclusions The apoptosis of iAPP is associated with inflammation and IL-1 may play an important role in the pathogenesis of iAPP related pancreatic islet cell toxicity. [ABSTRACT FROM AUTHOR]

目的探讨炎症因子白细胞介素1（IL-1）在人胰岛淀粉样多肽（iAPP）损伤胰岛细胞中 的作用。方法分离Wistar大鼠胰岛,鉴定细胞的活力并分为:正常对照组（A组）、iAPP 10 μmol/L孵 育组（B组）、10 μmol/L iAPP与10 mg/L IL-1受体阻滞剂（IL-1Ra）孵育组（C组）,各组均孵育24 h。膜 联蛋白V/碘化丙啶（Annexin-V/PI）荧光染色法检测胰岛细胞的凋亡,逆转录聚合酶链反应（RT-PCR） 检测炎症相关因子IL-1β和肿瘤坏死因子（TNF）mRNA的表达以及凋亡相关因子Bax和Bcl-2 mRNA 的表达。两组间比较采用两独立样本t 检验,3组以上组间比较采用单因素方差分析LSD法检验。 结果（1）各组凋亡比率及凋亡相关基因的表达:荧光检测结果显示,细胞凋亡率B组高于A、C组 （[ 16.8±4.7）%比（1.2±0.4）%、（4.4±2.1）%,t=5.72、4.17,均P<0.05]。RT-PCR结果与荧光结果一致显 示,B组Bax mRNA表达量增加,而Bcl-2 mRNA表达量减少,分别为A组的（2.28±0.46）与（0.42±0.18） 倍（t=4.27、3.10,均P<0.05）;C组Bax mRNA表达量下降,而Bcl-2 mRNA表达量增加,分别为B组的 （0.48±0.17）与（1.93±0.25）倍,差异均具有统计学意义（t=3.41、3.23,均P<0.05）。（2）各组炎症因子的表 达:B组IL-1β和TNF mRNA表达量增加,分别是A组的（4.25±1.64）与（3.19±1.04）倍（t=3.39、3.49,均 P<0.05）;C组中两者表达量均下降,分别是B组的（0.32±0.11）与（0.28±0.11）倍,差异均具有统计学意 义（t=2.94、3.65,均P<0.05）。结论iAPP造成的胰岛细胞凋亡与炎症损伤有关,IL-1信号通路在其中 发挥了重要作用. [ABSTRACT FROM AUTHOR]

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