Shukla Shivendra D, Kansra Sanjay V, Reddy M A, Shukla Sundeep M, Klachko David M, Sturek Michael
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, USA.
Comp Med. 2008 Oct;58(5):481-4.
Responses of platelets from diabetic and diabetic-hyperlipidemic pigs were studied. Pigs were made diabetic with single dose of alloxan, which acts by selectively destroying insulin-producing pancreatic beta cells thus inducing type 1 diabetes. Pigs were kept for 1 or 12 wk, during which thrombin-induced aggregation was monitored in washed platelets. The platelets showed increased sensitivity to aggregation within 1 wk of induction of diabetes. Hyperlipidemia alone for 12 wk did not increase platelet hypersensitivity, but hyperlipidemia together with diabetes significantly increased thrombin-induced platelet aggregation. Because this hypersensitivity occurred in washed platelets, this characteristic appears to be independent of any contribution by plasma factors or other blood cells. The hypersensitivity of platelets from diabetic pigs correlated with decreased activity of mitogen-activated protein kinase. These studies offer the first evidence that platelet hyperactivity occurs during the early stages (within a week) of induction of diabetes in pigs and before manifestation of other cardiovascular problems.
研究了糖尿病猪和糖尿病高脂血症猪血小板的反应。用单剂量的四氧嘧啶使猪患糖尿病,四氧嘧啶通过选择性破坏产生胰岛素的胰腺β细胞起作用,从而诱发1型糖尿病。将猪饲养1周或12周,在此期间监测洗涤血小板中凝血酶诱导的聚集情况。在糖尿病诱导后的1周内,血小板对聚集的敏感性增加。单独高脂血症12周不会增加血小板超敏反应,但高脂血症与糖尿病一起会显著增加凝血酶诱导的血小板聚集。由于这种超敏反应发生在洗涤血小板中,这种特性似乎与血浆因子或其他血细胞的任何作用无关。糖尿病猪血小板的超敏反应与丝裂原活化蛋白激酶活性降低相关。这些研究提供了首个证据,表明在猪糖尿病诱导的早期阶段(1周内)且在其他心血管问题出现之前,血小板就出现了活性亢进。