壳聚糖稳定的硒纳米颗粒与二甲双胍协同挽救高脂饮食/链脲佐菌素诱导的糖尿病大鼠的睾丸氧化损伤和类固醇生成相关基因失调。
Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.
作者信息
Abd El-Hakim Yasmina M, Abdel-Rahman Mohamed Amany, Khater Safaa I, Hamed Arisha Ahmed, Metwally Mohamed M M, Nassan Mohamed A, Hassan Manal Ewaiss
机构信息
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 4511, Egypt.
Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 4511, Egypt.
出版信息
Antioxidants (Basel). 2020 Dec 27;10(1):17. doi: 10.3390/antiox10010017.
BACKGROUND
this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model.
METHODS
control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed.
RESULTS
in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups.
CONCLUSIONS
the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.
背景
本研究检测了二甲双胍（MF）和/或壳聚糖稳定化硒纳米颗粒（CH-SeNPs）对高脂饮食联合低剂量链脲佐菌素（HFD/STZ）诱导的2型糖尿病（T2DM）大鼠模型雄性生殖功能损伤的缓解作用。
方法
使用对照非糖尿病组、HFD/STZ糖尿病组、HFD/STZ+MF组、HFD/STZ+CH-SeNPs组和HFD/STZ+MF+CH-SeNPs组大鼠。60天后，评估精液、激素检测、酶促抗氧化、脂质过氧化、睾丸组织病理学以及类固醇生成相关基因的mRNA表达。
结果
在HFD/STZ糖尿病大鼠中，精子数量和活力、雄性性激素以及睾丸抗氧化酶显著降低。然而，精子异常和睾丸丙二醛显著增加。在HFD/STZ糖尿病大鼠中，类固醇生成相关基因，包括类固醇生成急性调节蛋白（StAr）、细胞色素P450侧链裂解酶（CYP11A1）、细胞色素P450 17α-羟化酶（CYP17A1）和17-β-羟基类固醇脱氢酶3（HSD17B3），以及线粒体生物发生相关基因，包括过氧化物酶体增殖物激活受体γ辅激活因子1α（PGCα）和沉默调节蛋白（SIRT），均显著下调。然而，细胞色素P450芳香化酶（CYP19A1）mRNA表达显著上调。相比之下，口服MF和/或CH-SeNPs可显著挽救T2DM诱导的精子异常、降低精子活力、降低性激素水平、减轻睾丸氧化损伤以及改善类固醇生成相关基因失调。在MF和CH-SeNPs联合治疗组中，许多评估参数与单一MF或CH-SeNPs治疗组有很大差异。
结论
MF和CH-SeNPs联合治疗比单一治疗方法能更有效地限制糖尿病并发症，它们可被认为是T2DM的一种有前景的治疗选择。
Zotero 插件