Department of Obstetrics and Gynecology, and Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
Cannabis Cannabinoid Res. 2024 Apr;9(2):591-600. doi: 10.1089/can.2022.0242. Epub 2023 Feb 7.
The present study aimed to demonstrate the possible effects of increased 2-arachidonoylglycerol (2-AG) by applying the monoacylglycerol lipase inhibitor KML-29 on rats with ovarian ischemia-reperfusion (IR) model. Forty-eight female Wistar albino rats were divided into six groups. Group 1: Sham, Group 2: Ischemia, Group 3: IR, Group 4: IR + KML-29 (2 mg/kg), Group 5: IR + KML-29 (20 mg/kg), and Group 6: IR + vehicle (dimethyl sulfoxide). Three hours of ischemia followed by 3 h of reperfusion. Two different doses of KML-29 (2 and 10 mg/kg) were administered intraperitoneally in Groups 4 and 5, 30 min before reperfusion. Ovarian IR injury and ovarian reserve were evaluated histopathological and by using nuclear factor (NF)-κB, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, superoxide dismutase, glutathione peroxidase pre-/postoperative blood antimullerian hormone, and inhibin B. In the KML-1 and KML-2 groups, this damage was significantly reduced compared to the ischemia group. NF-κB, IL-1β, TNF-α, and TGF-β1 immunoreactivities increased statistically significantly in the ischemia group compared to the control group (<0.001). Immunoreactivities of these proteins were significantly decreased in the KML-1 and KML-2 groups (<0.001). It was observed that the number of these apoptotic cells decreased significantly in the KML-1 and KML-2 groups compared to the ischemia group (p<0.001). The postoperative inhibin level showed a significant decrease in the ischemia group compared to the sham group, while a significant increase was observed in the KML-1 and KML-2 groups compared to the ischemia group. It was seen that anti-inflammatory, antioxidant, and antiapoptotic activity was formed, and the ovarian reserve was preserved with 2-AG in ovarian IR damage. The protective effect of endocannabinoids on the ovaries may create a promising new treatment strategy for many pathologies that will affect the ovarian reserve.
本研究旨在通过应用单酰基甘油脂肪酶抑制剂 KML-29 来证明增加 2-花生四烯酸甘油（2-AG）对卵巢缺血再灌注（IR）模型大鼠的可能影响。将 48 只雌性 Wistar 白化大鼠分为六组。第 1 组：假手术，第 2 组：缺血，第 3 组：IR，第 4 组：IR+KML-29（2mg/kg），第 5 组：IR+KML-29（20mg/kg），第 6 组：IR+载体（二甲基亚砜）。缺血 3 小时后再灌注 3 小时。第 4 组和第 5 组在再灌注前 30 分钟分别腹膜内给予两种不同剂量的 KML-29（2 和 10mg/kg）。通过组织病理学和核因子（NF）-κB、白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β1、超氧化物歧化酶、谷胱甘肽过氧化物酶、术前/术后抗苗勒管激素和抑制素 B 来评估卵巢 IR 损伤和卵巢储备。在 KML-1 和 KML-2 组中，与缺血组相比，这种损伤显著降低。与对照组相比，缺血组 NF-κB、IL-1β、TNF-α 和 TGF-β1 的免疫反应性显着增加（<0.001）。在 KML-1 和 KML-2 组中，这些蛋白质的免疫反应性显着降低（<0.001）。与缺血组相比，在 KML-1 和 KML-2 组中观察到这些凋亡细胞的数量显着减少（p<0.001）。与假手术组相比，缺血组术后抑制素水平显着降低，而与缺血组相比，KML-1 和 KML-2 组的抑制素水平显着升高。可见，2-AG 在卵巢 IR 损伤中形成抗炎、抗氧化和抗凋亡活性，保留卵巢储备。内源性大麻素对卵巢的保护作用可能为许多影响卵巢储备的疾病提供一种有前景的新治疗策略。
