卵巢激素和神经肽Y拮抗剂持续递送对去卵巢大鼠体重和重要器官影响的组织病理学评价

Z. Cason, H. Benghuzzi, M. Tucci
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摘要

卵巢激素和其他生物制剂的给药途径是治疗、预防或根除人类不同疾病的关键因素。许多研究证明,与传统的给药途径相比,使用持续给药的生物制剂更有效。迄今为止,文献缺乏确凿的研究,证明体重和重要器官形态的变化与神经肽Y拮抗剂和雌激素的持续递送有关,与完整和卵巢切除的成人相比。因此,本研究的目的是对卵巢激素和神经肽y拮抗剂对去卵巢大鼠体重和重要器官的持续递送进行组织病理学评估。取Sprague Dawley大鼠25只,分为卵巢完整对照组、假药组、OVX +雌激素组和NPY拮抗剂组。五组中的三组动物通过手术植入了一个TCP给药装置,该装置装有1.6 mg雌激素和1.6 mg NPY拮抗剂,假动物则植入空胶囊。通过手术将胶囊插入6节腰椎附近的肌肉中。这些动物在植入后两周被安乐死。比较体重分析,OVX +雌激素和OVX + NPY拮抗剂与完整对照动物相似。机体主要脏器的组织病理学检查显示,完整、OVX、假药和NPY拮抗剂低、高剂量处理动物的肾上腺、脾、肝、肺和心肌均无组织病理学改变。唯一的显著差异是在肾脏上观察到的,在接受雌激素治疗的动物中,肾小球显得大得多。从本研究中获得的总体结论表明,TCPL递送可以有效地用于持续水平的NPY管理,并且与传统方法相关的副作用显着减少。
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Histopathologic Evaluation of the Substained Delivery of Ovarian Hormones and Neuropeptide Y Antagonist on the Body Weights and Vital Organs of Ovarectomized Rats
The route of administration of ovarian hormones and other biologicals represent a key factor in the treatment, prevention or eradication of different diseases in humans. Many studies have documented that the use of sustained delivery of biologicals is more effective compared to conventional route of administration. To date, the literature is lacking studies that conclusively demonstrate the change on body weights and vital organ morphology associated with sustained delivery of Neuropeptide Y antagonist and estrogen compared to intact and ovariectomized adults as a model. Therefore, the purpose of this study represents a histopathologic evaluation of the sustained delivery of ovarian hormones and neuropeptide y antagonist on the body weight and vital organs of ovariectomized rats. A total of 25 Sprague Dawley rats were obtained and divided into five groups, intact control with ovaries, sham, OVX + estrogen, and NPY antagonist. Animals in three of the five groups were surgically implanted with a TCP drug delivery device loaded with 1.6 mg of estrogen and 1.6 mg of NPY antagonist, and the sham animals were implanted with empty capsules. The capsules were surgically inserted into the muscle adjacent to the six lumbar vertebra. The animals were euthanized at two weeks, post-implantation phases. An analysis of the body weights were compared, and the OVX + estrogen and the OVX + NPY antagonist were similar to the intact control animals. Histopathologic evaluation of the major body organs revealed no histopathological change in the adrenals, spleen, liver, lungs or heart muscles of the intact, OVX, sham and NPY antagonist low and high dose treated animals. The only significant difference was observed in the kidney, where the glomeruli appeared much larger in the estrogen treated animals. Overall conclusion obtained from this study demonstrated that TCPL delivery can be used effectively to administer NPY at sustained level with remarkable reduction in side effects that associated with conventional means.
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