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促红细胞生成素在预防卵巢组织移植中缺血再灌注损伤的作用。

The Effect of Erythropoietin in Preventing Ischemia-Reperfusion Injury in Ovarian Tissue Transplantation.

作者信息

Kolusari Ali, Okyay Ayşe Güler, Koçkaya Evrim Arzu

机构信息

1 Department of Obstetrics and Gynecology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.

2 Department of Obstetrics and Gynecology, Tayfur Ata Sokmen Medical Faculty, Mustafa Kemal University, Hatay, Turkey.

出版信息

Reprod Sci. 2018 Mar;25(3):406-413. doi: 10.1177/1933719117715127. Epub 2017 Jun 28.

Abstract

UNLABELLED

Condensation Erythropoietin improved the survival of follicles in ovarian grafts most likely by reducing ischemic injury, by improving neoangiogenesis, and by its antioxidant effects.

OBJECTIVE

Ovarian tissue cryopreservation and transplantation are the only options accepted for prepubertal girls and women requiring immediate chemotherapy. Ischemia-reperfusion injury is the main obstacle for ovarian tissue transplantation. In the present study, we aimed to evaluate the effects of recombinant human erythropoietin (EPO) on tissue viability in autotransplanted rat ovaries.

STUDY DESIGN

Seventeen female rats were randomized into 3 groups as sham control group (n = 5), EPO-treated group (n = 6), and EPO-untreated group (n = 6). Both ovaries were excised and transplanted into a subcutaneous pouch formed at the anterior abdominal wall in the EPO-treated and untreated groups. In the EPO group, 5000 U/kg EPO was applied as local injection to the site that ovarian tissue was placed and the dose was repeated with the same route at the end of the fourth week. After 2 months, ovaries were removed and blood samples were obtained. Levels of estradiol (E), vascular endothelial growth factor (VEGF), VEGF-C, and lipid hydroperoxidase (LPO) and the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were measured both in blood and tissue samples. Histopathological and morphometric analyses were also performed on tissue samples.

RESULTS

Considering serum levels, mean CAT was significantly higher ( P = .003) and mean SOD ( P = .033), LPO ( P = .050), VEGF ( P = .001), and VEGF-C ( P = .024) were significantly lower in the EPO-treated group than in the untreated group. Mean serum GPX levels were similar. Significantly higher levels of E were determined in the EPO group than in the untreated group. Highest serum E levels were found in the sham group ( P = .001). Tissue levels of GPX (1.23) and CAT (53.17) were significantly higher in the EPO group ( P = .002 and P = .001, respectively). However, tissue levels of SOD and LPO, VEGF, and VEGF-C levels were significantly lower in the EPO group than those in the untreated group ( P = .033, P = .050, P = .002, and P = .003, respectively). In tissue examination, the highest values of x, y axis and epithelial height were in the sham group. Mean value of the EPO group was found statistically significantly higher than that of the untreated group ( P ≤ .05). In terms of antral follicle count, ordering was found as sham > EPO-treated > EPO-untreated group. Follicle counts in the EPO group were significantly higher than those in the untreated group ( P ≤ 0.05).

CONCLUSION

Erythropoietin improved the survival of follicles in ovarian grafts most likely by reducing ischemic injury, by improving neoangiogenesis, and by its antioxidant effects.

摘要

未标记

促红细胞生成素凝聚物最有可能通过减轻缺血性损伤、促进新生血管形成及其抗氧化作用来提高卵巢移植中卵泡的存活率。

目的

卵巢组织冷冻保存和移植是青春期前女孩和需要立即化疗的女性唯一可接受的选择。缺血再灌注损伤是卵巢组织移植的主要障碍。在本研究中,我们旨在评估重组人促红细胞生成素(EPO)对自体移植大鼠卵巢组织活力的影响。

研究设计

17只雌性大鼠随机分为3组,即假手术对照组(n = 5)、EPO治疗组(n = 6)和未治疗EPO组(n = 6)。在EPO治疗组和未治疗组中,将双侧卵巢切除并移植到前腹壁形成的皮下囊袋中。在EPO组中,以5000 U/kg EPO局部注射到放置卵巢组织的部位,并在第四周结束时通过相同途径重复给药。2个月后,取出卵巢并采集血样。检测血液和组织样本中雌二醇(E)、血管内皮生长因子(VEGF)、VEGF-C和脂质过氧化酶(LPO)的水平以及谷胱甘肽过氧化物酶(GPX)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性。还对组织样本进行了组织病理学和形态计量学分析。

结果

就血清水平而言,EPO治疗组的平均CAT显著更高(P = 0.003),平均SOD(P = 0.033)、LPO(P = 0.050)、VEGF(P = 0.001)和VEGF-C(P = 0.024)显著低于未治疗组。平均血清GPX水平相似。EPO组的血清E水平显著高于未治疗组。假手术组的血清E水平最高(P = 0.001)。EPO组的组织GPX水平(1.23)和CAT水平(53.17)显著更高(分别为P = 0.002和P = 0.001)。然而,EPO组的组织SOD和LPO、VEGF和VEGF-C水平显著低于未治疗组(分别为P = 0.033、P = 0.050、P = 0.002和P = 0.003)。在组织检查中,假手术组的x、y轴和上皮高度的最高值。发现EPO组的平均值在统计学上显著高于未治疗组(P≤0.05)。就窦状卵泡计数而言,顺序为假手术组>EPO治疗组>未治疗EPO组。EPO组的卵泡计数显著高于未治疗组(P≤0.05)。

结论

促红细胞生成素最有可能通过减轻缺血性损伤、促进新生血管形成及其抗氧化作用来提高卵巢移植中卵泡的存活率。

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