Liu Chen, Li Qiong, Yang Yubin
Clinical Nutrition Department, Sun Yat-sen University Cancer Center, Guang Zhou, China.
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Ann Clin Lab Sci. 2019 Jan;49(1):16-22.
This study aims to investigate the role of X-linked inhibitor of apoptosis protein (XIAP) in the pathogenesis of premature ovarian failure (POF) and the effects of the Modified Bazhen Decoction (MBD) in the treatment of POF.
Twenty-four eight-week-old Sprague Dawley (SD) rats were randomly divided into four groups: control group, POF group, MBD treatment group, and Fufang Ejiao Syrup (FES) treatment group. After adaptive feeding for one week, 18 SD rats in the POF, MBD and FES groups were subcutaneously injected with D-galactose (dissolved in saline) at the back of neck for eight weeks (150 mg/kg/day) to establish the POF model. Six SD rats in the control group received equal volumes of subcutaneous injection of saline. Tail blood was collected, and the concentration of follicle stimulating hormones (FSHs) and estradiol (E2) was measured, in order to evaluate the success of the POF model. SD rats in the MBD and FES treatment groups were intragastrically administered with MBD (10 ml/kg/day) and FES (10 ml/kg/day), respectively. Rats in the control and POF groups were intragastrically administered with saline (10 ml/kg/day). After four weeks of intragastrical administration with different medicines and saline, ovarian tissues were collected; and the expression level of XIAP, miR-23a and miR-27a were measured and compared among different groups.
Compared with the control group, XIAP expression was significantly lower, and miR-23a and miR-27a expression significantly higher in the POF group. Furthermore, XIAP expression was significantly higher, and miR-23a and miR-27a expression was significantly lower in the MBD group.
XIAP is involved in the regulation of oocyte and granulosa cells via the cysteinyl aspartate specific proteinase (caspase) pathway, and plays an important role in POF. MBD can dramatically activate XIAP, but inhibit the expression of miR-23a and miR-27a; preventing the apoptosis of oocyte and granulosa cells. Our study suggests that MBD may be a useful traditional Chinese medicine for the treatment of POF.
本研究旨在探讨X连锁凋亡抑制蛋白(XIAP)在卵巢早衰(POF)发病机制中的作用,以及加味八珍汤(MBD)治疗POF的效果。
将24只8周龄的Sprague Dawley(SD)大鼠随机分为四组:对照组、POF组、MBD治疗组和复方阿胶浆(FES)治疗组。适应性喂养1周后,POF组、MBD组和FES组的18只SD大鼠于颈部皮下注射D-半乳糖(溶于生理盐水),连续8周(150mg/kg/天)以建立POF模型。对照组的6只SD大鼠皮下注射等量生理盐水。采集尾血,检测卵泡刺激素(FSH)和雌二醇(E2)浓度,以评估POF模型是否成功建立。MBD治疗组和FES治疗组的SD大鼠分别灌胃给予MBD(10ml/kg/天)和FES(10ml/kg/天)。对照组和POF组大鼠灌胃给予生理盐水(10ml/kg/天)。不同药物和生理盐水灌胃4周后,采集卵巢组织;检测并比较不同组XIAP、miR-23a和miR-27a的表达水平。
与对照组相比,POF组XIAP表达显著降低,miR-23a和miR-27a表达显著升高。此外,MBD组XIAP表达显著升高,miR-23a和miR-27a表达显著降低。
XIAP通过半胱氨酸天冬氨酸特异性蛋白酶(caspase)途径参与卵母细胞和颗粒细胞的调控,在POF中起重要作用。MBD可显著激活XIAP,但抑制miR-23a和miR-27a的表达;防止卵母细胞和颗粒细胞凋亡。我们的研究表明,MBD可能是一种治疗POF的有效中药。