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阿利吉仑——一种通过肾素-血管紧张素-醛固酮系统(RAAS)保护大鼠卵巢缺血/再灌注损伤的有前景的策略。

Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS.

作者信息

Bayir Yasin, Cadirci Elif, Polat Beyzagul, Kilic Baygutalp Nurcan, Albayrak Abdulmecit, Karakus Emre, Un Harun, Keles Mevlut Sait, Kocak Ozgeris Fatma Betul, Toktay Erdem, Karaca Mehmet, Halici Zekai

机构信息

a Department of Biochemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.

b Department of Pharmacology , Faculty of Medicine, Ataturk University , Erzurum , Turkey.

出版信息

Gynecol Endocrinol. 2016 Aug;32(8):675-683. doi: 10.3109/09513590.2016.1153055. Epub 2016 Mar 3.

Abstract

The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1β, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system.

摘要

本研究旨在评估直接肾素抑制剂阿利吉仑作为抗氧化剂和组织保护剂的作用,并评估大鼠卵巢实验性缺血及缺血/再灌注损伤中的分子、生化和组织病理学变化。48只雌性大鼠被随机分为8组:第1组仅进行假手术。第2组接受100mg/kg阿利吉仑并进行假手术。第3组进行3小时的双侧卵巢缺血。第4组接受3小时缺血,随后再灌注3小时。第5组和第6组分别接受50mg/kg和100mg/kg阿利吉仑,并进行双侧卵巢缺血(缺血3小时后,双侧卵巢手术切除)。第7组和第8组分别给予50mg/kg和100mg/kg阿利吉仑,并诱导缺血。在3小时缺血期结束时,移除双侧血管夹,继续进行3小时再灌注。实验结束后,测定大鼠卵巢中白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α和诱导型一氧化氮合酶mRNA表达以及超氧化物歧化酶、谷胱甘肽、丙二醛、肾素和血管紧张素-II水平,并检查组织病理学变化。阿利吉仑治疗使缺血和缺血/再灌注损伤中细胞因子和氧化应激标志物的过度变化恢复正常。组织病理学上,阿利吉仑治疗改善了缺血和/或缺血/再灌注组织损伤的发展。本研究得出结论,阿利吉仑治疗通过改善氧化应激、减轻炎症和抑制肾素-血管紧张素-醛固酮系统,有效逆转缺血和/或缺血/再灌注诱导的卵巢损伤。

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