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维生素 B12 对卵巢缺血再灌注损伤相关炎症中 TLR-4/NF-κB 信号通路的影响。

The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation.

机构信息

Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.

Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.

出版信息

Int Immunopharmacol. 2022 Jun;107:108676. doi: 10.1016/j.intimp.2022.108676. Epub 2022 Mar 4.

DOI:10.1016/j.intimp.2022.108676
PMID:35255301
Abstract

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1β (IL-1β) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1β, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue.

摘要

卵巢缺血是一种妇科急症,由卵巢扭转引起。氧化应激和炎症在缺血/再灌注损伤的发展中起核心作用。我们研究了维生素 B12(被认为具有抗氧化特性)对缺血/再灌注期间卵巢中氧化应激和 Toll 样受体 4(TLR-4)/核因子 kappa B(NF-κB)信号通路的影响。48 只大鼠随机分为六组,设计如下:对照组(C)、缺血组(I)、缺血+维生素 B12 组(I+B12)、缺血-再灌注组(I/R)、I/R+维生素 B12 组(I/R+B12)和假手术+维生素 B12 组。维生素 B12 以 400 mcg/kg 的剂量通过腹腔途径每日一次给药,共给药 3 天,然后进行 I/R 程序。组织白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)和丙二醛(MDA)水平在 I/R 后升高,而谷胱甘肽(GSH)水平降低。此外,还观察到广泛的充血、水肿、出血和滤泡缺陷。NF-κB 和 TLR-4 的表达水平也在 I/R 组中增加。用维生素 B12 治疗后,GSH 水平升高,IL-1β、IL-6、MDA、NF-κB 和 TLR-4 水平降低。此外,给予维生素 B12 后,卵巢组织无水肿、轻度充血,滤泡正常。结果表明,I/R 导致卵巢组织发生显著的组织损伤,增加氧化应激和炎症。然而,维生素 B12 的应用是有效的,是减少与 I/R 相关的卵巢组织中炎症和氧化应激引起的损伤的替代药物。

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