Wells Monique Y, Voute Hélène, Bellingard Valérie, Fisch Cécile, Boulifard Virginie, George Catherine, Picaut Philippe
Ipsen Innovation, Les Ulis, France.
Toxicol Pathol. 2010 Feb;38(2):258-66. doi: 10.1177/0192623309357953. Epub 2010 Jan 25.
Subcutaneous injection of pharmaceutical compounds into the dorsal skin of rats is common in preclinical and nonclinical studies. However, no detailed histologic description of this anatomic location has been published to date. Following the observation of vascular lesions in the dorsum of rats in a thirteen-week toxicity study, a complementary study was performed on untreated Sprague-Dawley rats to evaluate the normal histology of the skin and subcutis, the potential effect of chronic subcutaneous injection on the morphology of the skin and its vasculature, and the spontaneous vascular pathology in the areas used as injection sites in the principal study. This study showed that saline injection did not fundamentally alter the morphology of the injection sites used for the principal study. Skin thickness was greater in males than in females. Although acellular intimal thickening occurred spontaneously in the dorsal skin of untreated males and females, only males had a spontaneous incidence of intimal hyperplasia. No site predilection for intimal lesions was apparent for either sex. Saline injection, or the physical trauma of injection, may induce intimal hyperplasia; males appear more likely to develop the lesion than do females. It is possible that acellular intimal thickening can progress to intimal hyperplasia under appropriate conditions.
在临床前和非临床研究中，将药物化合物皮下注射到大鼠背部皮肤是很常见的。然而，迄今为止尚未发表关于该解剖位置的详细组织学描述。在一项为期13周的毒性研究中观察到大鼠背部出现血管病变后，对未处理的斯普拉格-道利大鼠进行了一项补充研究，以评估皮肤和皮下组织的正常组织学、慢性皮下注射对皮肤及其血管形态的潜在影响，以及在主要研究中用作注射部位的区域的自发性血管病理学。这项研究表明，注射生理盐水并未从根本上改变主要研究中使用的注射部位的形态。雄性大鼠的皮肤厚度大于雌性。虽然未处理的雄性和雌性大鼠背部皮肤均自发出现无细胞内膜增厚，但只有雄性出现内膜增生的自发发生率。两种性别均未表现出内膜病变的部位偏好。注射生理盐水或注射造成的物理创伤可能会诱发内膜增生；雄性似乎比雌性更易发生这种病变。在适当条件下，无细胞内膜增厚有可能发展为内膜增生。
