Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats.
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.
Nobukata
H
H
Toxicology Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan. h-nobu@mochida.co.jp
Ishikawa
T
T
Obata
M
M
Shibutani
Y
Y
D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000503:physiopathology; D001779:Blood Coagulation Factors / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D005343:Fibrinolytic Agents / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000032:analysis / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D015415:Biomarkers; D001779:Blood Coagulation Factors; D001786:Blood Glucose; D005343:Fibrinolytic Agents; D007328:Insulin; D008055:Lipids