Vaginal permeability and enzymatic activity studies in normal and ovariectomized rabbits
Vaginal permeability and enzymatic activity studies in normal and ovariectomized rabbits
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DOI：
10.1023/a:1016016120392
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发表时间：
1996-05-01
影响因子：
3.7
通讯作者：
Robinson, JR
中科院分区：
文献类型：
--
作者：
Acarturk, F;Robinson, JR
目的.本研究的目的是建立一个动物模型，使用卵巢切除的兔子，绝经后的人，在体外阴道组织渗透性和氨肽酶活性的基础上。脑啡肽衍生物[D-ala（2），N-甲基-phe（4）-乙二醇（5）] [酪氨酰-3，5-H-3]脑啡肽（[H-3] RX 783006）对氨基肽酶和二肽基肽酶具有相对的酶稳定性，将其用作渗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，对正常和卵巢切除后的阴道组织进行组织学检查。与完整动物相比，卵巢切除动物的药物阴道渗透性显著增加。卵巢切除后，整个阴道组织变薄，粘膜上皮厚度减少约2倍，去势兔的阴道细胞通常不成熟。氨肽酶活性，亮氨酸氨肽酶，氨肽酶B和A，是相同的阴道组织匀浆和全组织标本在正常和卵巢切除兔，而氨肽酶N的活性显着降低卵巢切除相比，正常兔。根据目前的数据，卵巢切除兔可能是有用的动物模型，绝经后阴道研究。
Purpose. 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.Methods. An enkephalin derivative [D-ala(2),N-methyl-phe(4)-glycol(5)] [tyrosyl-3,5-H-3] enkephalin ([H-3] 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.Results. 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.Conclusions. Based on the present data, the ovariectomized rabbit may be useful as an animal model for postmenopausal vaginal studies.