Streptozocin affects the hepatorenal function of type 1 diabetes mini-pigs

doi:10.3969/j.issn.2095-4344.2013.18.019

Abstract

Abstract:

BACKGROUND: It is an acknowledged method to establish type 1 diabetes models in mini-pigs with high doses of streptozocin, but there are few reports about its influence on hepatorenal function of animals.
OBJECTIVE: To explore the effect of high-dose streptozocin on hepatorenal function in type 1 diabetes mini-pigs.
METHODS: Obama mini-pigs were randomly divided into control group and model group. Before and 10 and 30 minutes, 1, 2 and 4 hours, 1, 3 and 7 days after ear vein administration of sodium citrate or streptozocin, the blood samples were obtained respectively, and used to dynamically monitor the fasting blood-glucose, C peptide and insulin levels, and the hepatorenal function was examined. Glucose transporter protein 2 expression levels in pancreas, liver and kidney were determined by Western blot.
RESULTS AND CONCLUSION: Since 24 hours after administration, fasting blood-glucose was increased significantly in the model group and maintained at 17.7-20.1 mmol/L, while the C peptide and insulin levels were decreased significantly. Compared with pre-administration, the total protein, alanine aminotransferase, aspartic acid transaminase and creatinine levels were not changed significantly in the model group; urea nitrogen and albumin levels were slightly decreased, but did not reach significant difference level; the blood uric acid was significantly reduced (P < 0.05). Western blot results showed that the expressions of glucose transporter-2 of pancreas, liver and renal basilar membrane cells in the model group were significantly lower than those in the control group. One-time high-dose streptozocin injection can establish the mini-pig model of type 1 diabetes successfully, and has no significant influence on the hepatorenal function.

Key words: organ transplantation, basic experiment in organ transplantation, diabetes, type 1 diabetes, glucose transporter-2, mini-pig, hepatorenal function, provincial grants-supported paper

CLC Number:

R318

Tian Zhong, Cui Yong-chun, Li Kai, Li Ju-bo, Wang Kun, Tang Yue. Streptozocin affects the hepatorenal function of type 1 diabetes mini-pigs[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(18): 3366-3373.

Figures/Tables 3

为了进一步确定糖尿病分型，实验于给药后1周进行了静脉葡萄糖耐量试验和C肽释放试验。静脉葡萄糖耐量试验实验结果表明，与给药前水平相比，模型组链脲佐菌素处理后7 d空腹血糖水平明显高于7 mmol/L的糖尿病诊断标准，空腹胰岛素水平显著下降；对照组注射等体积0.1 mol/L柠檬酸钠前后的空腹血糖和胰岛素水平差异不明显。静脉注射50%葡萄糖后1 h，对照组和模型组动物血糖均明显升高，模型组达到28 mmol/L左右(>11.1 mmol/L临界值)，对照组9.5 mmol/L左右(<11.1 mmol/L临界值)；在注糖2 h后对照组血糖恢复至空腹水平，但模型组仍维持在较高水平(约25 mmol/L)；在静脉注糖后1 h，对照组动物血胰岛素水平升至空腹水平的4倍，但2 h降至空腹水平；而模型组小型猪在静脉注糖前后，血胰岛素始终变化不明显。见图1B，C。 C肽释放规律检测结果与血胰岛素变化情况相近，见图1D。链脲佐菌素处理后1周，模型猪血胰岛素空腹水平较给药前明显降低；注糖后一两小时与空腹水平比较，差异均无显著性意义。根据2010年ADA糖尿病诊断标准，上述参数变化特征符合1型糖尿病标准：空腹血糖大于等于7 mmol/L；静脉葡萄糖耐量试验经脉注射50%葡萄糖1 h后血糖浓度>11.1 mmol/L，血糖2 h后血糖浓度未降至空腹水平；空腹胰岛素和C肽水平明显降低，静脉注射50%葡萄糖前后2 h内，二者血液水平始终变化不显著。说明小型猪静脉一次性注射高剂量链脲佐菌素(150 mg/kg)可成功建立1型糖尿病模型。 2.3 给药前后1型糖尿病猪模型的肝肾功能为说明一次性静脉注射高剂量链脲佐菌素建立小型猪糖尿病模型是否能够造成肝肾功能损伤，实验分别在给药前和给药后1周采集了各组实验小型猪的静脉血，进行肝肾功的检查。结果表明，给药前实验小型猪的各项指标均正常。给药后1周，血总蛋白、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、肌酐水平均在正常范围内；而白蛋白和尿素氮较给药前略有降低，但尚未达到显著水平；仅尿酸水平与正常值相比差异有显著性意义，较给药前降低约10倍，见表1。"

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