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施书梅,姜培培,王晓燕,黄爱红.二陈汤对PCOS大鼠卵巢中NF-κB和NLRP3介导炎症反应的调控作用[J].湖南中医药大学学报,2023,43(6):968-973[点击复制] |
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二陈汤对PCOS大鼠卵巢中NF-κB和NLRP3介导炎症反应的调控作用 |
施书梅,姜培培,王晓燕,黄爱红 |
(海安市中医院妇产科, 江苏 南通 226600;海安市中医院脑病科, 江苏 南通 226600) |
摘要: |
目的 研究二陈汤对多囊卵巢综合征(polycystic ovary syndrome, PCOS)大鼠卵巢中核因子-κB(factor-kappa-B, NF-κB)和NOD样受体蛋白3(NOD-like receptor protein 3, NLRP3)介导炎症反应的调控作用及意义。方法 将成年雌性SD大鼠随机分成空白对照组、PCOS组、二陈汤组、二甲双胍组。空白对照组给予普通饲料喂养,PCOS组、二陈汤组和二甲双胍组均采用来曲唑灌胃联合高脂饲料喂养的方式进行PCOS造模;空白对照组和PCOS组进行生理盐水灌胃,二陈汤组进行二陈汤灌胃,二甲双胍组进行二甲双胍灌胃,共30 d。采用HE染色检测卵巢组织形态学变化;采用试剂盒检测血清黄体生成素(luteinizing hormone, LH)、卵泡刺激素(follicle stimulating hormone, FSH)、雌二醇(estradiol, E2)、睾酮(testosterone, T)、抗米勒管激素(anti mullerian hormone, AMH)、总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、空腹血糖(fasting blood glucose, FBG)、空腹胰岛素(fasting insulin, FINS)、C反应蛋白(C-reactive protein, CRP)、白细胞介素-1β(interleukin-1β, IL-1β)、白细胞介素-6(interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平;计算胰岛素抵抗指数(HOMA-IR);采用Western blot检测卵巢组织中TLR4、NF-κB、NLRP3、ASC、Caspase-1的表达水平。结果 PCOS组大鼠卵巢组织中可见大量囊状扩张卵泡和闭锁卵泡,未见优势卵泡,黄体减少;血清LH、T、AMH、TC、TG、FBG、FINS、CRP、IL-1β、IL-6、TNF-α水平,LH-FSH、HOMA-IR水平,卵巢组织中TLR4、NF-κB、NLRP3、ASC、Caspase-1的表达水平高于空白对照组(P<0.05),血清FSH、E2水平低于空白对照组(P<0.05)。二陈汤组和二甲双胍组卵巢组织中可见各级卵泡、黄体增多;血清LH、T、AMH、TC、TG、FBG、FINS、CRP、IL-1β、IL-6、TNF-α水平,LH-FSH、HOMA-IR水平,卵巢组织中TLR4、NF-κB、NLRP3、ASC、Caspase-1的表达水平低于PCOS组,血清FSH、E2水平高于PCOS组(P<0.05)。结论 二陈汤可显著改善PCOS大鼠的卵巢形态学特征、内分泌紊乱并减轻炎症状态,抑制卵巢组织中NF-κB和NLRP3介导的炎症反应可能是相关的分子机制。 |
关键词: 多囊卵巢综合征|二陈汤|胰岛素抵抗|炎症反应|核因子-κB|NOD样受体蛋白3 |
DOI:10.3969/j.issn.1674-070X.2023.06.002 |
投稿时间:2022-11-21 |
基金项目:南通市卫生健康委员会科研项目(QB2020015)。 |
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Regulation of Erchen Decoction on NF-κB and NLRP3 mediated inflammatory response in ovaries of rats with polycystic ovary syndrome |
SHI Shumei,JIANG Peipei,WANG Xiaoyan,HUANG Aihong |
(Department of Gynecology and Obstetrics, Hai'an Hospital of Chinese Medicine, Nantong, Jiangsu 226600, China;Department of Encephalopathy, Hai'an Hospital of Chinese Medicine, Nantong, Jiangsu 226600, China) |
Abstract: |
Objective To study the regulation of Erchen Decoction on nuclear factor-kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) mediated inflammatory response in ovaries of rats with polycystic ovary syndrome (PCOS), and to discuss the significance. Methods Adult female SD rats were randomly divided into blank group, PCOS group, Erchen Decoction group, and metformin group. Blank group was given normal feeding while PCOS group, Erchen Decoction group, and metformin group were all given letrozole by gavage combined with high-fat diet to establish PCOS model. After modeling, blank group and PCOS group were given normal saline by gavage, while Erchen Decoction group and metformin group were given corresponding drugs by gavage respectively for a total of 30 days. The ovarian histomorphological changes were detected by hematoxylin and eosin (HE) staining, while the levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), anti mullerian hormone (AMH), total cholesterol (TC), triglyceride (TG), fasting blood glucose (FBG), fasting insulin (FINS), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by kits. Then the insulin resistance index (HOMA-IR) was measured. And the expression levels of toll-likereceptor 4 (TLR4), NF-κB, NLRP3, ASC, and cysteinyl aspartate specific proteinase-1 (Caspase-1) in ovarian tissue were measured by Western blot. Results In rats of PCOS group, there were a large number of expanded follicles and atresia follicles but no dominant follicles, and the corpus lutea decreased. The levels of serum LH, T, AMH, TC, TG, FBG, FINS, CRP, IL-1β, IL-6, and levels of TNF-α, LH/FSH ratio, and HOMA-IR were higher than those of rats in blank group, so were the expression levels of TLR4, NF-κB, NLRP3, ASC, Caspase-1 in rat ovarian tissue (P<0.05), while the levels of serum FSH and E2 were lower than those of rats in blank group (P<0.05). There were follicles at all levels and the corpus lutea increased in rat ovarian tissue in Erchen Decoction group and metformin group. In these two groups, the levels of serum LH, T, AMH, TC, TG, FBG, FINS, CRP, IL-1β, IL-6, and levels of TNF-α, LH/FSH ratio, and HOMA-IR were lower than those of rats in PCOS group, so were the expression levels of TLR4, NF-κB, NLRP3, ASC, and Caspase-1 in rat ovarian tissue, while the levels of serum FSH and E2 were higher than those of rats in PCOS group (P<0.05). Conclusion Erchen Decoction can significantly improve the ovarian morphological features and relieve endocrine disorders in rats with PCOS. Meanwhile, it can reduce inflammation and inhibit NF-κB and NLRP3 mediated inflammatory response in the ovarian tissue. |
Key words: polycystic ovary syndrome|Erchen Decoction|insulin resistance|inflammatory response|nuclear factor-kappa-B|NOD-like receptor protein 3 |
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