出 处:《中医药学报》2022年第9期25-31,共7页Acta Chinese Medicine and Pharmacology
基 金:国家自然科学基金项目(81760806);甘肃省中医药管理局项目(GZK-2019-28);甘肃省高等学校创新能力提升项目(2019B-103);甘肃省教育厅项目(0706-05)。
摘 要:目的:探讨早衰和初老大鼠下丘脑、垂体和卵巢组织FSHR、LHR和ER蛋白表达的差异以及左归丸的干预作用。方法:60只大鼠给予顺铂注射液6 mg/(kg·w),共2次,建立卵巢早衰大鼠模型。空白组给予等剂量的生理盐水腹腔注射。将造模成功的大鼠随机分为模型组、补佳乐组、左归丸(低、中、高)剂量组;另40只初老大鼠,随机分成空白组、左归丸(低、中、高)剂量组,每组10只。用免疫组化法定位和相对定量早衰和初老大鼠在下丘脑-垂体-性腺轴上的FSHR、LHR和ER的表达量差异;不同剂量左归丸干预POF(早衰和初老)大鼠,检测FSHR、LHR和ER的表达量。结果:早衰大鼠血清卵泡雌激素(FSH)水平明显增高(P<0.05),卵泡雌激素受体(FSHR)在早衰大鼠下丘脑组织和初老组大鼠下丘脑、垂体和卵巢组织表达下调(P<0.05),黄体生成素受体(LHR)在早衰大鼠下丘脑、垂体组织和初老组大鼠垂体组织表达下调(P<0.05),雌激素受体(ER)在早衰大鼠下丘脑、垂体、卵巢组织和初老大鼠垂体组织表达下调(P<0.05);左归丸可以上调早衰大鼠卵巢组织,初老大鼠垂体和卵巢组织FSHR表达,早衰和初老大鼠垂体组织LHR以及早衰和初老大鼠下丘脑、垂体和卵巢组织ER表达,尤以左归丸高剂量组作用显著(P<0.05)。结论:下丘脑、垂体和卵巢组织FSHR和ER低表达是造成卵巢功能衰退的主要原因,左归丸通过促进卵巢合成分泌雌激素(E),降低血清FSH和LH水平,进而上调下丘脑、垂体和卵巢组织的FSHR和ER表达,延缓卵巢衰退。Objective: To investigate effects of Zuogui Pill on the protein expressions of FSHR, LHR and ER of hypothalamus-pituitary-ovary(HPO) axis in rats with premature ovarian failure(POF) and in early-aging rats. Methods: 60 rats were established the model of POF by the injection of Cisplatin(6 mg/kg·w, twice). The rats with successful modeling were randomly divided into the model group, the Bujiale(Estradiol Valerate Tablet) group, the Zuogui Pill groups of low-dose, medium-dose and high-dose. Another 40 early-aging rats were randomly divided into the blank group, the Zuogui Pill groups of low-dose, medium-dose and high-dose. The expression levels of FSHR, LHR and ER of HPO axis were measured by immunohistochemical method and relative quantification method in each group. Results: The level of serum follicular estrogen(FSH) was significantly increased in POF rats(P<0.05), and the expression of follicular estrogen receptor(FSHR) was down-regulated in hypothalamus of POF rats and in hypothalamus, pituitary and ovary of early-aging rats(P<0.05). The expression of luteinizing hormone receptor(LHR) was down-regulated in hypothalamus and pituitary tissues of POF rats and in pituitary tissues of early-aging rats(P<0.05), and the expression of estrogen receptor(ER) was also down-regulated in hypothalamus, pituitary and ovarian tissues of POF rats and pituitary tissues of early-aging rats(P<0.05). Zuogui Pill could up-regulate the expression of FSHR in the ovarian tissues of POF rats and in the pituitary and ovarian tissues of the early-aging rats, LHR in the pituitary tissues of the early-aging rats and POF rats, as well as the expression of ER in the hypothalamus, pituitary and ovarian tissues of the POF rats and early-aging rats;for which Zuogui Pill of high-dose had the most obvious effect(P<0.05). Conclusion: The low expression of FSHR and ER in hypothalamus, pituitary and ovarian tissues is the main cause of ovarian function decline. Zuogui Pill can promote the synthesis and secretion of estrogen(E) in the ovary, reduce
关 键 词:卵巢功能早衰(POF) 下丘脑-垂体-卵巢轴(HPO) FSHR LHR ER
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