小剂量链脲佐菌素致大鼠Beta细胞损伤模型探讨

Low streptozotocin dose-induced rat beta cell damage model

  • 摘要: 目的 建立小剂量链脲佐菌素(streptozotocin,STZ)致大鼠Beta细胞损伤模型,探讨Beta细胞损伤后胰岛的自身免疫性情况和Beta细胞自我修复能力。 方法 SD大鼠腹腔注射40 mg/kg STZ,3 d后测量随机血糖、空腹血糖和空腹C-肽,并进行胰腺组织HE染色、胰岛素和CD8α免疫组化染色。于第54天进行口服葡萄糖耐量实验,第56天检测随机血糖、空腹血糖、空腹C-肽和CD8α免疫组化染色。 结果 给予40 mg/kg剂量STZ处理后,第3天大鼠随机血糖实验组(33.00±2.31) mmol/L,空白对照组(5.72±0.63) mmol/L明显增高,而空腹血糖实验组(4.03±0.48) mmol/L,空白对照组(3.50±0.41) mmol/L未见异常,C-肽水平实验组(0.23±0.03) ng/ml,空白对照组(0.29±0.03) ng/ml降低,胰岛素免疫组化显示Beta细胞受损,CD8α免疫组化显示在胰岛的周边部存在阳性细胞表达。56 d时血糖趋势及CD8α表达与3 d时相同,但C-肽水平STZ组高于空白对照组,葡萄糖耐量受损。 结论 小剂量STZ损伤大鼠Beta细胞后,Beta细胞分泌功能降低,CD8α阳性细胞持续聚集继续损伤Beta细胞,最终可建立一种轻度损伤的1型糖尿病大鼠模型。

     

    Abstract: Objective To study the autoimmunity of pancreas and self-repair of beta cells by establishing the low streptozotocin (STZ) dose- induced rat beta cell damage model. Methods Three days after SD rats were injected with STZ (40 mg/kg), their blood glucose, fasting blood glucose and fasting C-peptide levels were measured. Their pancreatic tissue samples were stained with H&E, insulin and CD8α. Their oral glucose tolerance was tested on day 54 and their blood glucose, fasting blood glucose, C-peptide levels and CD8α staining were measured on day 56. Results The blood glucose level was significantly higher in experimental group and blank control group than in fasting blood glucose group on day 3 after STZ treatment at the dose of 40mg/kg (33.00±2.31 mmol/L and 5.72±0.63 mmol/L vs 4.03±0.48 mmol/L). No significant change in blood glucose level was found in blank control group (3.50±0.41 mmol/L). The C-peptide level was higher in blank control group than in experimental group (0.29±0.03 ng/ml vs 0.23±0.03 ng/ml). Insulin immunohistochemistry showed beta cell damage and CD8αimmunohistochemistry showed positive expression of beta cells around the pancreas. The blood glucose level and CD8αexpression level were identical on day 3 after STZ treatment. However, the C-peptide level was higher in STZ treatment group than in blank control group with impaired glucose tolerance. Conclusion The secretion function of beta cells decreases and the aggregated CD8α-positive cells further damage the beta cells after the beta cells are damaged by low STZ doses.

     

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