Acartürk F, Robinson J R
School of Pharmacy, Gazi University, 06330-Etiler-Ankara-Turkey.
Pharm Res. 1996 May;13(5):779-83. doi: 10.1023/a:1016016120392.
This study was initiated to develop an animal model, using ovariectomized rabbits, for the post-menopausal human, based on in vitro vaginal tissue permeability and aminopeptidase activity.
An enkephalin derivative [D-ala(2),N-methyl-phe(4)-glycol(5)][tyrosyl-3,5-(3)H] enkephalin {[(3)H] RX 783006), which has relative enzymatic stability to aminopeptidases and dipeptidyl peptidase, was used as a model peptide drug for permeability experiments. Aminopeptidase activity in vaginal homogenates, as well as in tissue pieces, was determined using 4-methoxy-2-naphthylamides of leucine, alanine, arginine, and glutamic acid as specific substrates. In addition, histological examination of normal and ovariectomized vaginal tissues was performed.
Vaginal permeability of the drug was significantly increased in the ovariectomized compared to the intact animal. The full vaginal tissue became thinner and mucosal epithelial thickness was reduced about two-fold after ovariectomization and vaginal cells from the castrated rabbit were typically immature. Aminopeptidase activity, leucine aminopeptidase, aminopeptidase B and A, was the same in vaginal tissue homogenates and whole-tissue specimens in both normal and ovariectomized rabbits whereas the activity of aminopeptidase N was significantly decreased in ovariectomized as compared to normal rabbits.
Based on the present data, the ovariectomized rabbit may be useful as an animal model for postmenopausal vaginal studies.
本研究旨在基于体外阴道组织通透性和氨肽酶活性，开发一种以去卵巢兔为模型的绝经后人类动物模型。
一种对氨肽酶和二肽基肽酶具有相对酶稳定性的脑啡肽衍生物[D-ala(2),N-甲基-phe(4)-甘醇(5)][酪氨酸-3,5-(3)H]脑啡肽{[(3)H]RX 783006}被用作通透性实验的模型肽药物。使用亮氨酸、丙氨酸、精氨酸和谷氨酸的4-甲氧基-2-萘酰胺作为特异性底物，测定阴道匀浆以及组织块中的氨肽酶活性。此外，对正常和去卵巢阴道组织进行了组织学检查。
与完整动物相比，去卵巢动物的药物阴道通透性显著增加。去卵巢后，整个阴道组织变薄，黏膜上皮厚度减少约两倍，去势兔的阴道细胞通常不成熟。正常和去卵巢兔的阴道组织匀浆和全组织标本中，氨肽酶活性，即亮氨酸氨肽酶、氨肽酶B和A相同，而去卵巢兔中氨肽酶N的活性与正常兔相比显著降低。
基于目前的数据，去卵巢兔可能作为绝经后阴道研究的动物模型。
