Shinbori Chiko, Saito Motoaki, Kinoshita Yukako, Satoh Itaru, Kono Tomoharu, Hanada Takuya, Nanba Eiji, Adachi Kaori, Suzuki Hiroto, Yamada Masashi, Satoh Keisuke
Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University Faculty of Medicine, 86 Nishimachi, Yonago, 683-8503, Japan.
Eur J Pharmacol. 2007 Jul 12;567(1-2):139-44. doi: 10.1016/j.ejphar.2007.04.009. Epub 2007 Apr 20.
We studied the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
我们研究了环己烯基长链脂肪醇（正二十六醇）对大鼠主动脉糖尿病性血管病变的影响。雄性斯普拉格-道利大鼠分为4组，一组为对照组，其他3组通过腹腔注射链脲佐菌素（50 mg/kg）诱导糖尿病。糖尿病诱导4周后，这3组大鼠再接受4周的溶剂或正二十六醇（2或8 mg/kg，每天腹腔注射）治疗。为了确定糖尿病血管功能障碍的机制以及正二十六醇的作用，我们对大鼠主动脉中的毒蕈碱M(3)受体、内皮型和诱导型一氧化氮合酶（eNOS和iNOS）mRNA进行了器官浴研究和实时聚合酶链反应。正二十六醇治疗并未改变糖尿病状态，但改善了去甲肾上腺素引起的糖尿病诱导的过度收缩以及乙酰胆碱诱导的大鼠主动脉受损的内皮依赖性舒张。此外，在糖尿病大鼠中，毒蕈碱M(3)受体和iNOS mRNA均显著增加，而正二十六醇逆转了这些上调。然而，eNOS mRNA的表达在所有组中均无变化。这些结果表明，正二十六醇对功能障碍具有有益作用，并逆转了糖尿病大鼠主动脉中毒蕈碱M(3)受体和iNOS mRNA的上调。
