Establishment of rat model of type 2 diabetes induced by streptozotocin combined with cerebral ischemic reperfusion injury

Abstract

Abstract:

AIM: To investigate an optimized rat model establishment of type 2 diabetes mellitus (T2DM) induced by streptozotocin (STZ) combined with cerebral ischemic reperfusion injury (T2DM-MCAO/R) so as to help the study of new drug for acute cerebral ischemia/reperfusion injury subjected to type 2 diabetes mellitus (T2DM). METHODS: High-fat and high-sugar (HFG) diet for 4 or 5 weeks were administered to induce insulin resistance, and STZ of different doses were injected to induce T2DM model. Models of T2DM-MCAO/R were built through five methods (A, B, C, D, E) with different doses of streptozotocin (STZ). Method A, B and C developed T2DM-MCAO/R injury models by surgery with sutures into brain from CCA; Method D and E, sutures from ECA. Method A administered drugs along with reperfusion; Method B and C injected drugs every day from reperfusion to 72 h; Method D and E, drugs were injected every day for two weeks before surgery. Syndrome, weight and fasting blood glucose (FBG) were assessed in various stages, and neurological behavioral scores were measured after the surgery to assess the quantity and quality of successful models. RESULTS: With method A-E, 80%, 77.8%, 84.6%, 100%, 100% rats were successfully modeled. While 93.3% rats were successfully induced T2DM model by method E with the highest success rate and lowest death rate. Nimodipine and insulin could all improve the fasting blood glucose level, neurological deficits and reduced infarction volume percentage at the same time. CONCLUSION: Rat model of T2DM-MCAO/R injury established by two times injection of low dose STZ and MCAO/R surgery (introduced from ECA) present higher successful modeling rate, lower death rate and better stability. It is referential to investigate the effect and mechanism of new medicine for preventing and treating ischemia/reperfusion injury subjected to T2DM.

Key words: type 2 diabetes mellitus, streptozotocin, reperfusion injury

CLC Number:

R965.2

LIU Chang, JIANG Daoli, LIU Xiaofang, XU Jia, WANG Lijue, WANG Qian, XU Ling, FANG Yi. Establishment of rat model of type 2 diabetes induced by streptozotocin combined with cerebral ischemic reperfusion injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(5): 518-525.

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