隐丹参酮调节SDF-1/CXCR4轴对卵巢功能不全大鼠的保护作用
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篇名: 隐丹参酮调节SDF-1/CXCR4轴对卵巢功能不全大鼠的保护作用
TITLE: Protective effect of cryptotanshinone on premature ovarian insufficiency rats by regulating the SDF-1/CXCR4 axis
摘要: 目的 基于基质细胞衍生因子1(SDF-1)/趋化因子CXC亚家族受体4(CXCR4)轴,探究隐丹参酮对卵巢功能不全(POI)大鼠的保护作用及潜在机制。方法采用腹腔注射乙烯基环己烯(VCD)的方法建立POI大鼠模型,并将造模成功的大鼠分为模型组、隐丹参酮低剂量组(50mg/kg)、隐丹参酮高剂量组(100mg/kg)、隐丹参酮高剂量+AMD3100组(100mg/kg隐丹参酮+2.5mg/kgCXCR4抑制剂AMD3100),每组10只;另取大鼠10只,以生理盐水代替VCD注射,作为对照组。各药物组大鼠灌胃或(和)腹腔注射相应药液,每天1次,连续4周。检测各组大鼠血清中雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)水平和卵巢组织中活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平,观察其卵巢组织形态,检测其卵巢组织细胞凋亡情况以及其中SDF-1、CXCR4mRNA和胱天蛋白酶3(caspase-3)、B细胞淋巴瘤2(Bcl-2)、Bcl-2关联X蛋白(Bax)、SDF-1、CXCR4蛋白的表达情况。结果与对照组比较,模型组大鼠卵巢萎缩,原始卵泡数量减少,闭锁卵泡数量增多,损伤明显;其血清中E2水平,卵巢组织中SOD、GSH-Px水平,以及卵巢组织中SDF-1、CXCR4mRNA的表达和Bcl-2、SDF-1、CXCR4蛋白的表达均显著降低或下调;血清中FSH和LH水平,卵巢组织中ROS和MDA水平,细胞凋亡率,以及卵巢组织中caspase-3、Bax蛋白的表达均显著升高或上调(P<0.05)。与模型组比较,隐丹参酮低、高剂量组大鼠卵巢组织病变明显好转,各定量指标均显著改善(P<0.05);AMD3100可显著逆转隐丹参酮对上述指标的改善作用(P<0.05)。结论隐丹参酮可通过激活SDF-1/CXCR4轴来减少POI大鼠卵巢组织细胞凋亡,减轻氧化应激,调节血清激素水平,进而改善卵巢损伤。
ABSTRACT: OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency (POI) rats and its potential mechanism based on stromal cell-derived factor-1 (SDF-1)/CXC subfamily receptor 4 (CXCR4) axis. METHODS POI rat model was established by intraperitoneal injection of vinylcyclohexene (VCD). The successfully modeled rats were randomly divided into model group, cryptotanshinone low-dose group (50 mg/kg), cryptotanshinone high-dose group (100 mg/kg), and cryptotanshinone high-dose+AMD3100 group (100 mg/kg cryptotanshinone+2.5 mg/kg CXCR4 inhibitor AMD3100), with 10 rats in each group. Another 10 rats were injected with normal saline instead of VCD as the control group. Rats in each drug group were given intragastrical or (and) intraperitoneal injection of the corresponding drug once a day for 4 weeks. The levels of estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum and reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in ovarian tissue were detected in each group. The morphology of ovarian tissue was observed. The cell apoptosis of ovarian tissue, as well as the mRNA expressions of SDF-1, CXCR4 and the protein expressions of caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), SDF- 1, CXCR4 were detected. RESULTS Compared with the control group, the ovarian atrophied, the number of primitive follicles decreased, the number of atretic follicles increased, and the damage was obvious in the model group. Serum E2 level, SOD and GSH-Px levels in ovarian tissue, the mRNA expressions of SDF-1 and CXCR4, and the protein expressions of Bcl-2, SDF-1 and CXCR4 in ovarian tissue were all significantly decreased or down-regulated; the levels of FSH and LH in serum, ROS and MDA levels in ovarian tissue, the cell apoptosis rate, and the protein expressions of caspase-3 and Bax in ovarian tissue mail:k26awn@163.com were increased or upregulated significantly (P<0.05). Compared with model group, the ovarian tissue lesions of rats in cryptotanshinone low-dose and high-dose groups were significantly improved, and each quantitative index was significantly improved (P<0.05). AMD3100 could significantly reverse the improvement effect of cryptotanshinone on the above indexes (P<0.05). CONCLUSIONS Cryptotanshinone can reduce ovarian cell apoptosis and oxidative stress in POI rats by activating the SDF-1/CXCR4 axis, regulating serum hormone levels, thereby improving ovarian injury.
期刊: 2024年第35卷第24期
作者: 瞿谆;马惠荣;冯丹;丑丹;张喻;李红梅
AUTHORS: QU Zhun,MA Huirong,FENG Dan,CHOU Dan,ZHANG Yu,LI Hongmei
关键字: 隐丹参酮;卵巢功能不全;氧化应激;激素;SDF-1/CXCR4轴
KEYWORDS: cryptotanshinone; premature ovarian insufficiency; oxidative stress; hormone; SDF-1/CXCR4 axis
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