1. Academic Validation
  2. Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats

Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats

  • Thromb Res. 2000 Jun 15;98(6):507-16. doi: 10.1016/s0049-3848(00)00196-1.
H Nobukata 1 T Ishikawa M Obata Y Shibutani
Affiliations

Affiliation

  • 1 Toxicology Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan. h-nobu@mochida.co.jp
Abstract

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.

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