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5-氨基酮戊酸联合二价铁通过增强 HO-1 表达改善阴囊热应激诱导的生精损伤。

5-Aminolevulinic acid combined with ferrous iron ameliorates scrotal heat stress-induced spermatogenic damage by enhancing HO-1 expression.

机构信息

Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.

出版信息

Mol Biol Rep. 2023 Jun;50(6):4999-5011. doi: 10.1007/s11033-023-08462-w. Epub 2023 Apr 22.

Abstract

OBJECTIVE

To explore whether 5-Aminolevulinic acid combined with ferrous iron (5-ALA/Fe) could protect testicular tissues damage of mice subjected to heat stress (HS) and provide its underlying mechanisms.

METHODS

5-ALA/Fe was administered intragastrically to mice for 10 days, then exposed to a scrotal heat stress at 43°C for 20 min on third day. Testes were harvested for morphologic and histopathological examination, oxidative stress, apoptosis, heme oxygenase-1 (HO-1) and inflammation detection. The mitogen-activated protein kinases (MAPK) signaling pathway in testis and CD4FoxP3regulatory T (Treg) cells in spleen were also investigated.

RESULTS

Compared to control group, the testis weight decreased and histological damage severed in HS group. Besides, HS also increased the oxidative stress, apoptosis and inflammation in testis. However, these indicators were ameliorated after 5-ALA/Fe treatment but deteriorated after receiving ZnPPIX. The expression of HO-1 was increased both in HS group and 5-ALA/Fe group. The protein expression levels of MAPK proteins were activated by HS and inhibited by 5-ALA/Fe. The CD4FoxP3 Treg generation was reduced by HS and increased by 5-ALA/Fe.

CONCLUSION

In this study, we have demonstrated that 5-ALA/Fe ameliorated the spermatogenic damage induced by scrotal heat stress via up-regulating the expression of HO-1 and inhibiting MAPK mediated oxidative stress and apoptosis and inducing CD4Foxp3 Tregs to inhibit the inflammation induced by HS in mice.

摘要

目的

探讨 5-氨基酮戊酸(5-ALA)联合二价铁(5-ALA/Fe)是否能保护热应激(HS)小鼠的睾丸组织损伤,并探讨其潜在机制。

方法

连续 10 天给小鼠灌胃 5-ALA/Fe,第 3 天将其阴囊暴露于 43°C 的热应激中 20min。采集睾丸进行形态学和组织病理学检查、氧化应激、凋亡、血红素加氧酶-1(HO-1)和炎症检测。还研究了睾丸中的丝裂原激活蛋白激酶(MAPK)信号通路和脾脏中的 CD4FoxP3 调节性 T(Treg)细胞。

结果

与对照组相比,HS 组睾丸重量降低,组织学损伤加重。此外,HS 还增加了睾丸的氧化应激、凋亡和炎症。然而,5-ALA/Fe 治疗后这些指标得到改善,但接受 ZnPPIX 后恶化。HO-1 的表达在 HS 组和 5-ALA/Fe 组均增加。HS 激活了 MAPK 蛋白的表达,而 5-ALA/Fe 抑制了它们。HS 减少了 CD4FoxP3 Treg 的产生,而 5-ALA/Fe 增加了它的产生。

结论

在这项研究中,我们证明了 5-ALA/Fe 通过上调 HO-1 的表达、抑制 MAPK 介导的氧化应激和凋亡以及诱导 CD4Foxp3 Tregs 来抑制 HS 引起的炎症,从而改善阴囊热应激引起的生精损伤。

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