Nishida M, Miyagawa J I, Tokunaga K, Yamamoto K, Keno Y, Kobatake T, Yoshida S, Nakamura T, Odaka H, Ikeda H, Hanafusa T, Yamashita S, Kameda-Takemura K, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
J Lab Clin Med. 1997 Feb;129(2):200-7. doi: 10.1016/s0022-2143(97)90140-2.
It is generally thought that typical atherosclerotic lesions do not develop in the rodent. The Goto-Kakizaki (GK) rat is a nonobese strain in which a spontaneous type of non-insulin-dependent diabetes mellitus develops without apparent macroangiopathy. In our previous study, making ventromedial hypothalamic (VMH) lesions in GK rats induced hyperphagia and a further deterioration in glucose metabolism. In the current study, male GK rats in which VMH lesions were made were examined for vascular changes, with special reference to atherosclerotic lesions. Marked hyperglycemia in GK rats with VMH lesions (hereafter referred to as VMH lesion rats) was revealed over an observation period (plasma glucose levels 16 weeks after the operation: VMH lesion GK rats, 19.3 +/- 2.0 mmol/L, vs sham-operated GK rats, 10.1 +/- 1.3 mmol/L; p < 0.0001). Light microscopic observation of the descending aorta in VMH lesion GK rats 16 weeks after the surgery revealed that the intimal thickening and the number of infiltrating cells into the intima were significantly increased as compared with sham-operated GK rats (17531 +/- 3747 microm2 vs 3072 +/- 1192 microm2, p < 0.0001; 15.6 +/- 3.1 per one transverse section vs 6.8 +/- 2.5 per one transverse section, p < 0.0005). Electron microscopic observations demonstrated an increased number of microvilli and lysosomes in endothelial cells, infiltration of macrophages and lymphocytes into the intima, and migration of medial smooth muscle cells into the intima that are considered to be early events in atherosclerosis. These morphologic changes could be induced by a deterioration in glucose metabolism. This rat may thus be useful for studying the process of the initiation of atherosclerosis in diabetes mellitus.
一般认为啮齿动物不会发生典型的动脉粥样硬化病变。Goto-Kakizaki（GK）大鼠是一种非肥胖品系，会自发发生非胰岛素依赖型糖尿病，且无明显的大血管病变。在我们之前的研究中，对GK大鼠进行腹内侧下丘脑（VMH）损伤会导致食欲亢进和糖代谢进一步恶化。在本研究中，对制造了VMH损伤的雄性GK大鼠进行血管变化检查，特别关注动脉粥样硬化病变。在观察期内发现，制造了VMH损伤的GK大鼠（以下简称VMH损伤大鼠）出现明显的高血糖（术后16周血浆葡萄糖水平：VMH损伤GK大鼠为19.3±2.0 mmol/L，假手术GK大鼠为10.1±1.3 mmol/L；p<0.0001）。术后16周对VMH损伤GK大鼠的降主动脉进行光镜观察发现，与假手术GK大鼠相比，内膜增厚以及内膜中浸润细胞的数量显著增加（分别为17531±3747平方微米和3072±1192平方微米，p<0.0001；每一个横切面分别为15.6±3.1个和6.8±2.5个，p<0.0005）。电镜观察显示内皮细胞中的微绒毛和溶酶体数量增加，巨噬细胞和淋巴细胞浸润到内膜，以及中膜平滑肌细胞迁移到内膜，这些被认为是动脉粥样硬化的早期事件。这些形态学变化可能是由糖代谢恶化引起的。因此，这种大鼠可能有助于研究糖尿病中动脉粥样硬化的起始过程。
