高效抗逆转录病毒疗法共轭银纳米颗粒改善2型糖尿病大鼠的睾丸损伤。
Highly active antiretroviral therapy conjugated silver nanoparticle ameliorates testicular injury in type-2 diabetic rats.
作者信息
Olojede Samuel Oluwaseun, Lawal Sodiq Kolawole, Dare Ayobami, Moodley Roshila, Rennie Carmen Olivia, Naidu Edwin C S, Azu Onyemaechi Okpara
机构信息
Discipline of Clinical Anatomy, School of Laboratory Medicine & Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
Discipline of Physiology, School of Laboratory Medicine & Medical Sciences, College of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South Africa.
出版信息
Heliyon. 2021 Dec 9;7(12):e08580. doi: 10.1016/j.heliyon.2021.e08580. eCollection 2021 Dec.
Despite advances in managing human immunodeficiency virus (HIV) infection and success in the treatment prognosis using highly active antiretroviral therapy (HAART). The clinical efficacy of this regimen has been associated with increased adverse effects such as metabolic derangements and reproductive dysfunctions. These adverse effects necessitate a nanoparticle delivery vehicle like silver nanoparticles (AgNPs), a multi-functional drug delivery system, to transport the HAART to the viral reservoir site like testis. This study was therefore designed to evaluate the effects of HAART loaded AgNPs (HAART-AgNPs) on testicular oxidative stress markers, an inflammatory biomarker, and histomorphology in a rat model of diabetes. Thirty-six adult male Sprague-Dawley rats were randomly divided into two groups (n = 18) non-diabetic and fructose-streptozotocin (Frt-STZ) induced type 2 diabetes (T2DM). Thereafter, both groups were subdivided into three (n = 6) and treated with distilled water, HAART and HAART-AgNPs. HAART-AgNPs caused a significant increase (p < 0.05) in catalase (23.43 ± 0.92) level vs diabetic control (16.95 ± 1.04). Also, HAART-AgNP caused a significant reduction (p < 0.05) in malondialdehyde, interleukin-6 and blood glucose levels (1.94 ± 0.06, 93.65 3.6, 287.33 ± 22.85 respectively), compared to their respective diabetic control values (2.18 ± 0.12, 143.4 9.2, 372.16 ± 23.16). Furthermore, HAART-AgNPs mitigated tubular atrophy, basement membrane thickening, interstitial distension, fibrous elemental distortion and peri-interstitial tissue alterations in the testis of diabetic rats. The results from this study showed that administration of HAART-AgNPs to diabetic rats reduced testicular inflammation, improved glycaemic control, antioxidant status, and testicular histology. Therefore, conjugation of AgNP with HAART may cater for the reproductive dysfunction during the management of HIV infection.
尽管在人类免疫缺陷病毒（HIV）感染的管理方面取得了进展，并且在使用高效抗逆转录病毒疗法（HAART）治疗预后方面取得了成功，但该方案的临床疗效与代谢紊乱和生殖功能障碍等不良反应的增加有关。这些不良反应需要一种纳米颗粒递送载体，如银纳米颗粒（AgNPs），一种多功能药物递送系统，将HAART输送到睾丸等病毒储存部位。因此，本研究旨在评估负载HAART的AgNPs（HAART-AgNPs）对糖尿病大鼠模型睾丸氧化应激标志物、炎症生物标志物和组织形态学的影响。36只成年雄性Sprague-Dawley大鼠被随机分为两组（n = 18），非糖尿病组和果糖-链脲佐菌素（Frt-STZ）诱导的2型糖尿病（T2DM）组。此后，两组再细分为三组（n = 6），分别用蒸馏水、HAART和HAART-AgNPs进行治疗。与糖尿病对照组（16.95±1.04）相比，HAART-AgNPs使过氧化氢酶水平显著升高（p < 0.05）（23.43±0.92）。此外，与各自的糖尿病对照值（2.18±0.12、143.4±9.2、372.16±23.16）相比，HAART-AgNP使丙二醛、白细胞介素-6和血糖水平显著降低（p < 0.05）（分别为1.94±0.06、93.65±3.6、287.33±22.85）。此外，HAART-AgNPs减轻了糖尿病大鼠睾丸的肾小管萎缩、基底膜增厚、间质扩张、纤维成分扭曲和间质周围组织改变。本研究结果表明，给糖尿病大鼠施用HAART-AgNPs可减轻睾丸炎症、改善血糖控制、抗氧化状态和睾丸组织学。因此，将AgNP与HAART结合可能有助于在HIV感染管理期间解决生殖功能障碍问题。
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