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富血小板血浆(PRP)和己酮可可碱(PTX)联合应用对成熟和未成熟大鼠环磷酰胺诱导的卵巢早衰的保护作用。

The protective effect of co-administration of platelet-rich plasma (PRP) and pentoxifylline (PTX) on cyclophosphamide-induced premature ovarian failure in mature and immature rats.

机构信息

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Toxicol Mech Methods. 2022 Oct;32(8):588-596. doi: 10.1080/15376516.2022.2057264. Epub 2022 Apr 4.

Abstract

Cyclophosphamide (CP), as an antineoplastic agent, causes premature ovarian failure (POF) due to ovarian toxicity and subsequent infertility in women. Platelet-rich plasma (PRP) has accumulated significant attention in regenerative medicine. Pentoxifylline (PTX) as a methylxanthine derivative has been shown to have antioxidant and antiapoptotic properties. The aim of this study was to evaluate the protective effect of PRP and PTX on CP-induced POF. Fifty mature and immature female rats were assigned into five groups: control, CP (75 mg/kg, intraperitoneal [ip] on days 1 and 10 to induce POF), CP + PRP (200 μl, ip, half an hour after CP injection on day 1 and 10), CP + PTX (50 mg/kg, orally, half an hour after CP injection daily for 21 day), and CP + PRP + PTX. At the end of experiments on day 21, measurement of body weight, ovarian parameters (ovarian volume, follicular granulosa cell layers diameter, oocyte diameter, and the number of granulosa cells), measurement of ovarian hormone in sera for estradiol (E), and anti-Mullerian hormone (AMH), as well as biochemical assessment were performed.The results showed that CP significantly reduced the ovarian parameters, E, AMH, superoxide dismutase (SOD) activity and increased Malondialdehyde (MDA) levels compared to the control group ( < 0.001). Our results also indicated that all histomorphometric parameters and biochemical markers in CP-induced POF, were preserved close to normal by PRP and PTX treatments in both mature and immature rats ( < 0.001). Therefore, it is concluded that the co-administration of PRP and PTX can protect the ovary from CP-induced POF.

摘要

环磷酰胺 (CP) 作为一种抗肿瘤药物,由于卵巢毒性和随后的不孕,会导致女性卵巢早衰 (POF)。富含血小板的血浆 (PRP) 在再生医学中受到了广泛关注。己酮可可碱 (PTX) 作为黄嘌呤衍生物,已被证明具有抗氧化和抗凋亡作用。本研究旨在评估 PRP 和 PTX 对 CP 诱导的 POF 的保护作用。将 50 只成熟和未成熟雌性大鼠分为五组:对照组、CP(75mg/kg,腹腔内[ip]于第 1 天和第 10 天注射以诱导 POF)、CP+PRP(200μl,ip,于第 1 天和第 10 天 CP 注射后半小时)、CP+PTX(50mg/kg,口服,每天 CP 注射后半小时连续 21 天)和 CP+PRP+PTX。在第 21 天实验结束时,测量体重、卵巢参数(卵巢体积、卵泡颗粒细胞层直径、卵母细胞直径和颗粒细胞数量)、血清中卵巢激素雌二醇 (E) 和抗苗勒管激素 (AMH) 的测量,以及生化评估。结果表明,与对照组相比,CP 显著降低了卵巢参数、E、AMH、超氧化物歧化酶 (SOD) 活性并增加了丙二醛 (MDA) 水平(<0.001)。我们的结果还表明,在成熟和未成熟大鼠中,PRP 和 PTX 治疗均可使 CP 诱导的 POF 中的所有组织形态计量学参数和生化标志物接近正常(<0.001)。因此,可以得出结论,PRP 和 PTX 的联合给药可以保护卵巢免受 CP 诱导的 POF。

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