Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice

Q1 Health Professions Radiation Medicine and Protection Pub Date : 2025-02-01 Epub Date: 2024-12-06 DOI:10.1016/j.radmp.2024.12.002
Qiuhua Zhou , Yiquan Ou , Xiangsheng Tian , Yujun Ning , Yuwei Mao , Weichao Zhao , Dingxin Long
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Abstract

Objective

To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms.

Methods

Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR ​+ ​Rg1, Rg1), IR ​+ ​Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 ​d, followed by single-dose irradiation of 5 ​Gy X-ray irradiation (2 ​Gy/min) for the IR and IR ​+ ​Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis.

Results

Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ​± ​1.62 vs. IR ​+ ​Rg1: 33.93 ​± ​2.20, t ​= ​−13.23, P ​< ​0.05), and reduced sperm malformation rates (IR: 46.33 ​± ​2.18 vs. IR ​+ ​Rg1: 39.00 ​± ​1.67, t ​= ​7.33, P ​< ​0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ​± ​0.28 vs. IR ​+ ​Rg1: 1.81 ​± ​0.18, t ​= ​1.40, P ​< ​0.05) and modulated serum testosterone (IR: 4.47 ​± ​0.23 vs. IR ​+ ​Rg1: 6.65 ​± ​0.09, t ​= ​−2.18, P ​< ​0.05), GnRH (IR: 24.37 ​± ​0.92 vs. IR ​+ ​Rg1: 32.98 ​± ​1.33, t ​= ​−8.61, P ​< ​0.05), and FSH levels (IR: 1.41 ​± ​0.11 vs. IR ​+ ​Rg1: 2.69 ​± ​0.21, t ​= ​−1.28, P ​< ​0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice.

Conclusions

Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.

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人参皂苷Rg1通过SCF/PI3K/Akt/mTOR通路减轻小鼠颅照射引起的慢性睾丸损伤
目的研究人参皂苷Rg1是否能减轻颅照射对小鼠远端生殖功能的不良影响,并探讨其机制。方法雄性C57BL/6J小鼠40只,随机分为4组[对照组、辐照(IR)、IR + Rg1、Rg1)、IR + Rg1、Rg1组],腹腔注射人参皂苷Rg1治疗30 d, IR组和IR + Rg1组均给予5 Gy x射线单剂量照射(2 Gy/min)。三个月后,收集睾丸、全脑和血清样本进行分析。结果组织学染色、透射电镜、精子分析和免疫荧光显示,人参皂苷Rg1改善了睾丸结构和功能损伤,提高了精子数量(IR: 20.70±1.62 vs. IR + Rg1: 33.93±2.20,t =−13.23,P <;0.05),并降低精子畸形率(红外:46.33±2.18与红外+ Rg1: 39.00±1.67,t = 7.33, P & lt;0.05)。进一步的末端脱氧核苷酸转移酶介导的dutp -生物素缺口末端标记(TUNEL)和酶联免疫吸附试验(ELISA)表明,Rg1抑制睾丸细胞凋亡(IR: 3.21±0.28 vs. IR + Rg1: 1.81±0.18,t = 1.40, P <;0.05)和调制血清睾酮(红外:4.47±0.23与红外+ Rg1: 6.65±0.09,t =−2.18,P & lt;激性腺素释放素(0.05),红外:24.37±0.92与红外+ Rg1: 32.98±1.33,t =−8.61,P & lt;0.05),和FSH水平(红外:1.41±0.11与红外+ Rg1: 2.69±0.21,t =−1.28,P & lt;0.05)。此外,定量PCR和Western blot结果显示,Rg1下调了辐照小鼠SCF、p-PI3K、p-Akt和mTOR蛋白的表达。结论人参皂苷Rg1可能通过调控HPG轴和PI3K/Akt/mTOR通路抑制生殖细胞凋亡,从而减轻慢性睾丸结构和功能损伤,提示人参皂苷Rg1可能是治疗颅脑照射所致生殖障碍的潜在药物。
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来源期刊
Radiation Medicine and Protection
Radiation Medicine and Protection Health Professions-Emergency Medical Services
CiteScore
2.10
自引率
0.00%
发文量
0
审稿时长
103 days
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