Abstract: BACKGROUND: Diabetes belongs to the category of “diabetes” in traditional Chinese medicine. According to the development process and clinical manifestations of the disease, there are often different syndrome manifestations. In most cases, excessive heat mainly appears in the early stage, which is called excessive heat type diabetes, and deficiency of both qi and yin is mainly present in the middle and late stages, which is called deficiency of both qi and yin type diabetes. 
OBJECTIVE: To establish a mouse model of interior heat and diabetes by compound method, which can reflect the characteristics of traditional Chinese medicine symptoms, and lay a foundation for studying the evolution of diabetes and related drugs. 
METHODS: Thirty ICR mice were randomly divided into blank control group, short-term model group and long-term model group. The short-term model group was intraperitoneally injected with 40 mg/kg streptozotocin for 5 consecutive days, and then given 20 g/kg warm drugs via gavage for 14 days to establish the interior heat and diabetes model. On the basis of short-term models, the long-term model group was given the same dose of warm drugs for 21 days. The body mass, fasting blood glucose, water intake, food intake, urine volume and serum insulin levels of mice in each group were measured after modeling. Insulin resistance index and insulin sensitivity index were calculated. The activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were measured. Hematoxylin-eosin staining was used to detect the pathological changes of mouse pancreas. The study protocol was approved by the Animal Ethics Committee of Henan University of Chinese Medicine (approval No. DWLL202003270).
RESULTS AND CONCLUSION: Compared with the blank control group, the mice in the short-term and long-term model groups showed typical symptoms of diabetes, such as polydipsia, polyuria, body mass loss, rise in the rectal temperature (P < 0.05); the levels of fasting blood glucose and insulin resistance index were significantly increased; the levels of insulin sensitivity index were significantly decreased (P < 0.05); and the activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were significantly increased (P < 0.05). The pancreatic tissue of mice in the short-term and long-term model groups was damaged in varying degrees by pathological observation of the pancreas. Compared with the short-term model group, the long-term model group had more drinking, more food, more urine, slower growth of body mass, and significantly lower rectal temperature with the progression of the disease (P < 0.05); the levels of fasting blood glucose and insulin resistance index were significantly increased, while the levels of insulin sensitivity index were significantly decreased (P < 0.05); the activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were significantly decreased (P < 0.05). Pathological findings indicated that the pancreatic function was further damaged in the long-term model group as the disease progressed. To conclude, the combination of streptozotocin and warm drugs for modeling can improve the disease-syndrome further combination model of interior heat and diabetes, and in the model, the syndrome is evolved. The short-term model shows excessive heat and the long-term model shows deficiency of both qi and yin.

Key words: diabetes mellitus, interior heat and diabetes, animal model of disease-syndrome combination, syndrome evolution, short-term model, excessive heat type of diabetes mellitus, long-term model, deficiency of both qi and yin type of diabetes mellitus