归术益坤方通过调控LPS/TLR-4通路对多囊卵巢综合征大鼠的影响  

Exploring the effects of Guizhu Yikun formula in treating polycystic ovary syndrome basing on LPS/TLR-4 pathway

作　　者：林青 刘艳霞[1] 佟庆[1] 陈雨 颜芳 邢玉[1] LIN Qing;LIU Yanxia;TONG Qing;CHEN Yu;YAN Fang;XING Yu(Dongfang Hospital Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东方医院妇科,100078

出　　处：《环球中医药》2023年第9期1752-1758,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金青年项目(81904241)。

摘　　要：目的基于LPS/TLR-4通路探讨归术益坤方治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的潜在机制。方法将18只6周龄雌性SD大鼠随机分为空白组、模型组、中药组,每组6只,来曲唑灌胃复制PCOS大鼠模型,以归术益坤方进行干预。监测大鼠动情周期、体质量、身长,放免法检测血清睾酮(testosterone,T)水平,干化学法检测空腹血糖(fasting plasma glucose,FPG)水平,ELISA法检测血清白细胞介-18(interleukin-18,IL-18)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、脂多糖(lipopolysaccharide,LPS)水平,HE染色观察大鼠卵巢形态学变化,Western-blot法检测卵巢组织Toll样受体4(toll like receptor-4,TLR-4)表达水平。结果与空白组比较,模型组大鼠体质量显著升高(P<0.01),动情周期出现紊乱,T值(P<0.05)、FPG值(P<0.01)明显升高,卵巢组织呈多卵泡改变,血清LPS水平上升(P<0.05),炎症因子IL-18、TNF-α水平显著上升(P<0.01),TLR-4蛋白表达显著上调(P<0.01)。与模型组相比,中药组体质量显著下降(P<0.01),部分大鼠恢复正常动情周期,T水平降低(P<0.05),FPG水平显著降低(P<0.01),卵巢可见优势卵泡及黄体,血清LPS水平下降(P<0.05),IL-18水平明显降低(P<0.01),TLR-4蛋白表达显著下调(P<0.01)。结论归术益坤方可以降低PCOS大鼠体质量,促进其恢复卵巢功能,降低雄激素水平及空腹血糖水平,下调LPS、炎症因子及TLR-4的表达。归术益坤方治疗PCOS的作用可能是通过调控LPS/TLR-4通路实现的。Objective To investigate the potential mechanism of Guizhu Yikun formula in treating polycystic ovary syndrome(PCOS)basing on LPS/TLP-4 pathway.Methods Eighteen six-week’old SD rats were randomly divided into blank group,model group and TCM group.Rats were treated in letrozole to establish PCOS model.Rats in TCM group were treated in Guizhu Yikun formula.Observing the estrous cycles,weights,heights of these rats,and drawing blood through abdominal aorta,testing serum testosterone(T)level,fasting plasma glucose(FPG)level,serum IL-18 and TNF-α,serum LPS level.Taking out bilateral ovaries and observing them after HE staining and testing the expression of TLR-4 protein in these ovary tissues.Results Compared with rats in the blank group,weight of rats in the model group significantly increased(P<0.01),as well as the T(P<0.05)level and FPG(P<0.01)level.The estrous cycle of the model group was disordered.Ovaries of both sides were transformed into PCOS ovaries in varying degrees,observing multiple follicles after He staining.Serum LPS level(P<0.05)and related inflammatory factors(P<0.01),such as IL-18 and TNF-α,were increased.The expression of TLR-4 protein(P<0.01)was up-regulated significantly.On the contrary,compared with the rats in the model group,weight of rats in the TCM group significantly decreased(P<0.01).Some rats recovered to normal estrous cycle.Their T(P<0.05)and FPG(P<0.01)level are decreased as well.Their ovarian morphology was transformed to normal to a certain extent.Dominant follicles and corpus luteum were visible.Serum LPS level(P<0.05)and IL-18 level(P<0.01)are reduced.The expression of TLR-4 protein was down regulated(P<0.01).Conclusion Guizhu Yikun formula is able to reduce the weight of PCOS rats,and promote the recovery of ovarian function,decrease serum T level,FPG level,LPS level and related inflammatory factors level as well,after which TLR-4 protein expression was down regulated.Guizhu Yikun formula may treat PCOS through LPS/TLR-4 pathway.

关 键 词：多囊卵巢综合征 归术益坤方 脂多糖 TOLL样受体4 炎症因子 

分 类 号：R285.5[医药卫生—中药学]