Altered Fibrinogen and Prothrombin mRNA Expression in Streptozotocin-induced Diabetic Rats

Coagulation factors play an important role in macrovascular and macrovascular disease in diabetes. We studied the time-course of coagulation and fibrinolysis factors in plasma and hepatic levels of fibrinogen and prothrombin mRNA in streptozotocin (STZ) -induced diabetic rats. The hepatic mRNA levels for fibrinogen subunit polypeptides (α-, β- and γ-chains) and prothrombin were determined by quantitative reverse transcription-polymerase chain reaction at 24, 48, 72 hours, 1 and 8 weeks after injection of 50 mg/kg STZ. The plasma fibrinogen contents were increased at 24 and 72 hours in STZ-treated rats and returned to the control level at 1 week. At 8 weeks, plasma fibrinogen levels in control and STZ-treated rats were increased with no significant difference between the two groups of rats. However, the plasma thrombin-ATIII complex level significantly increased with a decrease in plasminogen level at 8 weeks after STZ treatment. The levels of β-chain fibrinogen mRNA increased at 24, 48 and 72 hours and returned to nearly control levels at 1 and 8 weeks. The a-chain fibrinogen mRNA levels decreased significantly to 71% and 84% at 1 and 8 weeks, respectively, whereas the y-chain fibrinogen mRNA levels decreased slightly at 24 hours and increased again at 48 and 72 hours. There were no significant changes in prothrombin mRNA levels at 24, 48, 72 hours or 1 week but levels were slightly decreased at 8 weeks. These results suggest that a moderate decrease in fibrinogen and prothrombin mRNA levels at 8 weeks may be sufficient to induce the hypercoagulation due to the long-term hyperglycemia observed in STZ-induced diabetic rats.