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  • 俞晓敏△,闻笔伟△,张俊洁*.罗格列酮改善脂多糖诱导慢性低度炎症大鼠的卵巢功能异常[J].第二军医大学学报,2019,40(12):1310-1316    [点击复制]
  • YU Xiao-min△,WEN Bi-wei△,ZHANG Jun-jie*.Rosiglitazone improves ovarian dysfunction of rats with chronic low-grade inflammation induced by lipopolysaccharide[J].Acad J Sec Mil Med Univ,2019,40(12):1310-1316   [点击复制]
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罗格列酮改善脂多糖诱导慢性低度炎症大鼠的卵巢功能异常
俞晓敏△,闻笔伟△,张俊洁*
0
(海军军医大学(第二军医大学)长海医院妇产科, 上海 200433
共同第一作者
*通信作者)
摘要:
目的 观察慢性低度炎症大鼠卵巢组织中过氧化物酶体增殖物激活受体(PPAR)的表达,并初步探究PPAR-γ激动剂罗格列酮对慢性低度炎症诱导的卵巢功能异常的影响。方法 以腹腔注射脂多糖(LPS)诱导的慢性低度炎症大鼠为动物模型。将200只大鼠随机分为对照组(NS组)和慢性低度炎症组(LPS组),每组100只,分别予腹腔注射生理盐水和LPS干预。在发情周期不同阶段(发情前期、发情期、发情后期和发情间期),通过检测2组大鼠血清中雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)和抗苗勒管激素(AMH)评估卵巢功能,利用蛋白质印迹法检测卵巢组织中PPAR-α、PPAR-δ和PPAR-γ的表达情况。将2组各80只大鼠分别随机分为2个亚组,每个亚组40只大鼠,分别予生理盐水和罗格列酮灌胃干预。灌胃14 d后,观察各亚组大鼠在发情周期不同阶段卵巢组织中促炎细胞因子[白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)]水平和卵巢功能。结果 与NS组相比,在发情周期不同阶段,LPS组大鼠血清中E2和AMH水平均下降(P均<0.05),FSH和LH水平均升高(P均<0.05);卵巢组织中PPAR-γ表达均降低(P均<0.05),而PPAR-α和PPAR-δ表达无明显变化(P均>0.05)。在发情周期不同阶段,LPS诱导的慢性低度炎症大鼠在口服罗格列酮后卵巢组织中促炎细胞因子IL-1β、IL-6和TNF-α水平均降低(P均<0.05),并且LPS诱导血清中降低的E2、AMH和升高的FSH、LH均得以改善(P均<0.05)。结论 PPAR-γ激动剂罗格列酮可减轻LPS诱导的大鼠慢性低度炎症反应,并改善卵巢功能。
关键词:  过氧化物酶体增殖物激活受体  罗格列酮  慢性低度炎症  脂多糖  卵巢功能异常
DOI:10.16781/j.0258-879x.2019.12.1310
投稿时间:2019-08-03修订日期:2019-10-28
基金项目:国家自然科学基金(81571387).
Rosiglitazone improves ovarian dysfunction of rats with chronic low-grade inflammation induced by lipopolysaccharide
YU Xiao-min△,WEN Bi-wei△,ZHANG Jun-jie*
(Department of Obstetrics and Gynecology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai 200433, China
Co-first authors.
* Corresponding author)
Abstract:
Objective To detect the expression of peroxisome proliferator-activated receptor (PPAR) in ovarian tissues of rats with chronic low-grade inflammation, and to explore the effect of PPAR-γ agonist rosiglitazone on ovarian dysfunction induced by chronic low-grade inflammation. Methods A chronic low-grade inflammation model of rats was established by intraperitoneal injection of lipopolysaccharide (LPS). Two hundred rats were randomly assigned to control group (NS group) and chronic low-grade inflammation group (LPS group), and the rats were intraperitoneally injected with normal saline and LPS, respectively. The ovarian function of rats was assessed by detecting the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) during different stages of the estrus cycle (proestrus, estrus, metestrus and diestrus). The protein expression levels of PPAR-α, PPAR-δ and PPAR-γ in ovarian tissues were detected using Western blotting. Eighty rats of each group were randomly divided into two subgroups, which were administered intragastrically by normal saline and rosiglitazone, respectively. Fourteen days after intragastric administration, the levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNF-α), in ovarian tissues and ovarian function of rats in each subgroup were observed during different stages of the estrus cycle. Results Compared with the NS group, during different stages of the estrus cycle, the serum levels of E2 and AMH of rats in the LPS group were significantly decreased (all P<0.05), while the serum levels of FSH and LH were significantly increased (all P<0.05). During different stages of the estrus cycle, the expression levels of PPAR-γ in ovarian tissues were significantly decreased in the LPS group compared with the NS group (all P<0.05), while the expression levels of PPAR-α and PPAR-δ were not significantly different between the two groups (all P>0.05). Compared with the intraperitoneal injection of LPS+intragastric administration of normal saline subgroup, during different stages of the estrus cycle, the expression levels IL-1β, IL-6 and TNF-α in ovarian tissues of rats were significantly decreased in the intraperitoneal injection of LPS+intragastric administration of rosiglitazone subgroup (all P<0.05), the serum levels of E2 and AMH were significantly increased (all P<0.05), and the serum levels of FSH and LH were significantly decreased (all P<0.05). Conclusion PPAR-γ agonist rosiglitazone can attenuate LPS-induced chronic low-grade inflammatory and improve ovarian function in rats.
Key words:  peroxisome proliferator-activated receptor  rosiglitazone  chronic low-grade inflammation  lipopolysaccharide  ovarian dysfunction