二陈汤调控谷胱甘肽过氧化物酶4/环氧化酶介导的氧化损伤及铁死亡改善多囊卵巢综合征的作用及机制  

Effects and mechanism of Erchen Decoction on the regulation of phospholipid hydroperoxide glutathione peroxidase/cyclooxygenase-2 mediated oxidative damage and ferroptosis on polycystic ovary syndrome

作　　者：丛培玮[1] 张丽娜[2] 王丹[3] 尚冰[4] 张林[5] CONG Pei-wei;ZHANG Li-na;WANG Dan;SHANG Bing;ZHANG Lin(Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Teaching and Experimental Center,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;School of Medical Laboratory,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Academy of Traditional Chinese Medicine Literature,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;College of Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学中医脏象理论及应用国家教育部重点实验室,沈阳110847 [2]辽宁中医药大学教学实验中心,沈阳110847 [3]辽宁中医药大学医学检验学院,沈阳110847 [4]辽宁中医药大学中医文献研究院,沈阳110847 [5]辽宁中医药大学中医学院,沈阳110847

出　　处：《中华中医药杂志》2023年第2期615-619,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.82104735);中国博士后科学基金第71批面上资助“地区专项支持计划”项目(No.2022MD713764);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金资助(No.zyzx2202);辽宁省自然科学基金项目(No.2019-ZD-0953);辽宁省教育厅科学技术研究项目(No.L202038)。

摘　　要：目的:基于多囊卵巢综合征(PCOS)“痰湿不孕”理论探讨二陈汤对PCOS的防治作用机制。方法:选取动情周期规律SD大鼠32只随机分为对照组(n=10),模型组(n=22),模型组给予高脂饲料+来曲唑溶液灌胃。造模结束后随机选取周期延长的大鼠(n=10)为治疗组,1 mL/100 g剂量连续4周灌胃给予二陈汤煎剂。HE染色法观察大鼠卵巢形态学变化,比色法检测血清及卵巢超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)水平变化,Western Blot法检测卵巢谷胱甘肽过氧化物酶4(GPX4)、环氧化酶-2(COX-2)和铁蛋白重链(FTH1)蛋白水平变化。结果:与对照组比较,模型组大鼠卵巢可见大量囊性扩张卵泡,闭锁卵泡及早期发育的小卵泡;血清、卵巢中SOD、GSH-Px水平显著降低(P<0.01),MDA水平显著升高(P<0.01);COX-2蛋白表达显著升高(P<0.05),GPX4、FTH1蛋白表达显著降低(P<0.05);与模型组比较,二陈汤治疗后大鼠卵巢囊性卵泡明显减少,黄体数量有所增加,出现少量正常发育的早期小卵泡;血清、卵巢中SOD、MDA、GSH-Px水平及卵巢中GPX4、COX-2和FTH1蛋白水平均有显著改善(P<0.01,P<0.05)。结论:二陈汤能显著改善PCOS卵巢情况,其机制可能与调控GPX4/COX-2介导的氧化损伤及抑制卵巢细胞铁死亡相关。Objective: To explore the effects of Erchen Decoction on PCOS and its possible mechanism based on the theory of ‘phlegm-dampness infertility’ of polycystic ovary syndrome(PCOS). Methods: Thirty-two SD rats with regular estrus cycle were randomly divided into control group(n=10) and model group(n=22). The model group was given high fat diet and letrozole solution by gavage. After modeling,rats in the extended model group(n=10) were randomly selected as the treatment group and given 1 mL/100 g intragastric administration for 4 consecutive weeks. The morphologic changes of ovaries were observed by HE staining,the levels of SOD,MDA and GSH-Px in serum and ovaries were detected by colorimetry,and the protein levels of GPX4,COX-2 and FTH1 in ovaries were detected by Western Blot. Results: Compared with the control group,there were a lot of cystic dilated follicles,atretic follicles and early developing small follicles in the ovary of the model group. The levels of SOD and GSH-Px in serum and ovary were significantly decreased(P<0.01),while the levels of MDA were significantly increased(P<0.01),the protein expression of COX-2 was significantly increased(P<0.05),and the protein expression of GPX4and FTH1 was significantly decreased(P<0.05). Compared with model group,after treatment with Erchen Decoction,cystic ovarian follicles were significantly reduced,the number of corpus luteum was increased,and there were a few small follicles in the early stage of normal development,the levels of SOD,MDA and GSH-Px in serum and ovary and the protein levels of GPX4,COX-2 and FTH1 in ovary were significantly improved(P<0.01,P<0.05). Conclusion: Erchen Decoction can significantly improve the ovarian condition of PCOS,the mechanism may be related to the regulation of GPX4/COX-2 mediated oxidative damage and inhibition of iron death of ovarian cells.

关 键 词：二陈汤 多囊卵巢综合征 氧化损伤 铁死亡 痰湿不孕 

分 类 号：R285.5[医药卫生—中药学]