聚肌苷酸-聚胞苷酸阻止非肥胖性糖尿病发病机制的研究

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目的 观察免疫调节剂聚肌苷酸 聚胞苷酸 (polyI:C)对非肥胖性糖尿病 (NOD)小鼠糖尿病发生和胰岛炎程度的影响以及干预后胰腺细胞Fas和Fas配体 (FasL)的表达变化情况。方法 给 36只 4周龄NOD雌鼠隔日腹腔注射 polyI :C 0 0 5 μg/g ,共 4周 ;同样方法注射等量的磷酸盐缓冲液 (PBS)作为对照。于 15周时各处死18只小鼠 ,取胰腺组织HE染色进行胰岛炎评分 ,反转录 多聚酶反应 (RT PCR)法检测FasmRNA和FasLmRNA的表达。其余小鼠 2 4周龄时观察发病率。结果 ① 2 4周龄时polyI:C干预组的发病率 11 1% ,明显低于PBS对照组的发病率 72 7% (P <0 0 1)。②polyI :C干预组胰岛炎评分指数明显低于PBS对照组 ,胰岛炎严重程度明显减轻 (P <0 0 1)。③PT PCR检测 polyI :C干预组胰腺FasmRNA表达低于PBS对照组 (P <0 0 1) ,而FasLmRNA表达差异无显著性。结论 polyI :C可以降低NOD小鼠糖尿病的发病率 ,延缓糖尿病的发生 ,减轻胰岛炎的严重程度 ,polyI:C通过抑制胰腺细胞Fas表达从而减少胰岛 β细胞的凋亡 ,在其干预机制中起一定作用 Objective To investigate the effects of poly I (C), an immunomodulator, on the development of diabetes and insulitis in non-obese diabetic (NOD) mice and the effects of Fas and Fas ligand Express changes. Methods Thirty-six 4-week-old NOD female mice were intraperitoneally injected with poly I: C 0 05 μg / g for 4 weeks. The same method was used to inject equal amount of phosphate buffered saline (PBS) as the control. At 15 weeks, 18 mice were sacrificed. Insulinitis was detected by HE staining of pancreatic tissues. The expression of Fas mRNA and FasL mRNA was detected by reverse transcriptase polymerase chain reaction (RT PCR). The remaining mice were observed incidence at 24 weeks of age. Results ① The incidence of polyI: C intervention group was 11 1% at 2 4 weeks of age, which was significantly lower than that of PBS control group (72 7%, P 0 01). ② The scores of insulitis in the polyI: C intervention group were significantly lower than those in the PBS control group, and the severity of insulitis was significantly reduced (P <0.01). ③ The expression of Fas mRNA in pancreas of PT-PCR-treated polyI: C group was lower than that of PBS control group (P <0.01), while FasL mRNA expression was not significantly different. Conclusion PolyI: C can reduce the incidence of diabetes mellitus, delay the onset of diabetes mellitus and reduce the severity of insulitis in NOD mice. PolyI: C can inhibit pancreatic β-cell apoptosis by inhibiting the expression of Fas in pancreatic cells Certain effect
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