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药物剂量烟酸对亚急性糖皮质激素诱导的大鼠睾丸损伤的影响。

Effects of pharmacological doses of niacin on subacute glucocorticoid-induced testicular damage in rats.

机构信息

Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Pharmacol Res Perspect. 2023 Oct;11(5):e01128. doi: 10.1002/prp2.1128.

Abstract

Glucocorticoid excess adversely affects male reproduction. This study evaluates effects of pharmacological doses of niacin on testicular structure and function in dexamethasone-treated rats. Adult rats (48) were randomly assigned to 6 equal groups: (1) Negative control (NC): normal rats; (2) Positive control (PC): dexamethasone at 7 mg/kg/day by intraperitoneal injections for 7 days; groups 3-6 (N50, N100, N200, and N400): dexamethasone and concomitant treatment with niacin at 50, 100, 200, and 400 mg/kg/day by oral gavages. Testicular weight and volume of PC rats were significantly lower than the NC group (p < .05). Testicular volume of rats in the N50 and N200 groups was statistically similar to the NC group. Significant decreases in serum testosterone with a slight LH increase were detected in the PC group. Nacin at 50 mg/kg reversed serum testosterone to NC levels and increased serum LH concentration. Niacin only slightly increased epididymal spermatozoa number while all groups of niacin-treated rats had significantly higher percentages of motile spermatozoa compared with the PC group. Hypospermatogenesis, germ cell degeneration and depletion, epithelial vacuolization, and degenerated Leydig cells were observed in PC rats. Lesions were relatively milder in niacin-treated rats. Johnsen scores were also significantly higher in niacin-treated rats. Niacin reduced apoptosis as shown by TUNEL assay. In conclusion, niacin administration at pharmacological doses dose-dependently ameliorates the destructive effects of dexamethasone on sperm motility, Johnsen score, and testicular cell apoptosis in rats with the latter can be considered a decisive mechanism for its positive effects on testis.

摘要

糖皮质激素过多会对男性生殖产生不利影响。本研究评估了烟酸在给予地塞米松的大鼠中对睾丸结构和功能的影响。成年大鼠(48 只)随机分为 6 组:(1)阴性对照组(NC):正常大鼠;(2)阳性对照组(PC):腹腔注射地塞米松 7mg/kg/天,共 7 天;(3)-(6)组(N50、N100、N200 和 N400):地塞米松和烟酸同时治疗,剂量分别为 50、100、200 和 400mg/kg/天,灌胃给药。PC 组大鼠睾丸重量和体积明显低于 NC 组(p<.05)。N50 和 N200 组大鼠睾丸体积与 NC 组相似。PC 组大鼠血清睾酮水平明显下降,lh 稍有升高。Nacin 50mg/kg 可将血清睾酮恢复至 NC 水平,并增加血清 LH 浓度。烟酸仅轻度增加附睾精子数量,而所有烟酸治疗组大鼠的活动精子百分比均明显高于 PC 组。PC 组大鼠出现少精子症、生精细胞变性和耗竭、上皮空泡化和变性的 Leydig 细胞。烟酸治疗组大鼠的病变相对较轻。烟酸治疗组的 Johnsen 评分也明显较高。TUNEL 检测显示,烟酸可减少细胞凋亡。综上所述,烟酸在药理学剂量下给药可剂量依赖性地改善地塞米松对大鼠精子活力、Johnsen 评分和睾丸细胞凋亡的破坏作用,后者可被认为是其对睾丸产生积极影响的决定性机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d624/10433454/5ec30ac33d88/PRP2-11-e01128-g004.jpg

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