STZ诱导糖尿病大鼠造模法中大鼠死亡原因探讨

Causes of Death in STZ-induced Rat Models of Diabetes Mellitus

中文关键词:  链脲佐菌素 大鼠模型 糖尿病 死亡原因

英文关键词:Streptozotocin (STZ) Rat model Diabetes mellitus Cause of death

中文摘要:

      目的 通过观察链脲佐菌素（STZ）诱导糖尿病（DM）大鼠模型建立过程中的一般状况，分析并探讨建立DM大鼠模型中存在的问题及注意事项，以期提高造模率。方法 雄性SD大鼠100只，随机分为2组，正常对照组（n=10）和实验组（n=90）。实验组采用STZ 65 mg/kg一次性腹腔注射的方式建立DM大鼠模型，注射STZ后根据是否达到成模标准，将实验组分为模型组和未成模组。监测各组大鼠的体质量、空腹血糖（FBG）、尿糖（UG）、尿蛋白（UP）、尿常规、肾功能、肝功能、血脂以及肾脏肥大指数（KHI）；死亡大鼠解剖并留取病变器官，通过HE染色观察大鼠病变器官的病理改变。结果 采用一次性腹腔注射STZ的方式建立DM模型的成模率为58.89%，死亡率为43.33%；与未成模组大鼠相比，模型组大鼠的体质量、进食量、饮水量、尿量、FBG、肌酐、尿素氮、KHI以及大鼠的死亡率和尿路感染的发生率均增高，而总蛋白、白蛋白、胆固醇以及甘油三酯水平降低，差异有统计学意义（P<0.05）。大体解剖及HE染色均证实有9只大鼠死于肺水肿，19只大鼠死于肾脓肿。另外，有11只大鼠死亡原因不明确。结论 65 mg/kg STZ一次性腹腔注射可以诱导DM大鼠模型的建立，但是死亡率高，可能与感染、营养不良、淋巴循环受阻、STZ本身的毒性以及环境气候条件的变化有关。

英文摘要:

      Objective To identify conditions that may improve the successful rate of STZ-induced rat models of diabetes mellitus (DM). Methods 100 male SD rats were randomly divided into control group (n=10) and experimental group (n=90). Rats in the experimental group were treated with intraperitoneal injection of STZ 65 mg/kg once, and were then categorized into succeeded DM model group and failed group. Their body masses and levels of fasting blood glucose (FBG), urine glucose （UG）, urine protein （UP）, urine routine, renal function, liver function, blood lipids and kidney hypertrophy index （KHI） were monitored and compared. Dead rats were dissected to observe diseased organs. Pathological changes of those diseased organs were examined by HE staining. Results DM rat models were established through a single intraperitoneal injection of STZ, with a success rate of 58.89%. During the experiment, 43.33% of rats died. Compared with the rats in the failed group, the DM rat models had significantly higher levels of body mass, food intake, water intake, urine output, FBG, creatinine, blood urea nitrogen, KHI, urinary tract infections, and mortality; but lower levels of total protein, albumin and cholesterol and triglyceride (P<0.05). Nine rats died of pulmonary edema; 19 died of renal abscess. The causes of 11 dead rats were not clear. Conclusion DM rat models can be established through a single intraperitoneal injection of STZ 65 mg/kg, but with high mortality rate. The deaths may be associated with infection, malnutrition, suffocation of lymphatic circulation, toxicity of STZ, and changes in environmental and climate conditions.