基于TLR-4/NF-κB信号通路探讨苍附导痰汤对痰湿型多囊卵巢综合征大鼠的治疗作用  

Investigation of the Therapeutic Effect of Cangfu Daotan Decoction on Polycystic Ovary Syndrome Rats of Phlegm-damp Type Based on TLR-4/NF-κB Signaling Pathway

作　　者：吴晓贞[1] 何嘉仑[1] 曾蕾[1] 邓高丕[1] WU Xiaozhen;HE Jialun;ZENG Lei;DENG Gaopi(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405

出　　处：《中药新药与临床药理》2022年第3期307-312,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医药局项目(20191115);广州中医药大学第一附属医院青年科研人才培优项目(2019QN26);邓高丕广东省名中医传承工作室项目(粤中医办函[2019]5号)。

摘　　要：目的基于TLR-4/NF-κB信号通路探讨苍附导痰汤对痰湿型多囊卵巢综合征(PCOS)模型大鼠的影响。方法将50只SD雌性大鼠随机分为空白组、模型组及中药(苍附导痰汤)低、中、高剂量组(3.12、6.24、12.48 g·kg^(-1))。采用Poresky造模法联合高脂饮食建立痰湿型PCOS病证结合大鼠模型。造模成功后采用相应剂量的苍附导痰汤灌胃给药,每日1次,连续28 d。采用苏木精-伊红(HE)染色法进行大鼠卵巢组织病理形态学观察;采用ELISA法测定血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)等炎性因子水平;采用qRT-PCR法检测卵巢组织中核因子κB(NF-κB)、Toll样受体4(TLR-4)、氧化型低密度脂蛋白(ox-LDL)mRNA表达;采用免疫组织化学法检测卵巢组织中高迁移率族蛋白1(HMGB1)的表达。结果与空白组比较,模型组大鼠卵巢的成熟卵泡数和黄体数明显减少(P<0.05);血清IL-6、TNF-α和CRP水平明显升高(P<0.05);卵巢组织中NF-κB、TLR-4及ox-LDL mRNA表达及HMGB1蛋白表达均明显上调(P<0.05)。与模型组比较,中药中、高剂量组大鼠卵巢的成熟卵泡数、黄体数均明显增加(P<0.05);大鼠血清IL-6、TNF-α、CRP水平明显下降(P<0.05);卵巢组织中NF-κB、ox-LDL、TLR-4 mRNA表达及HMGB1蛋白表达均明显下调(P<0.05)。结论苍附导痰汤可能通过下调HMGB1的表达,抑制TLR-4/NF-κB信号通路,进而减少IL-6、TNF-α、CRP等炎性因子的释放,从而发挥对PCOS的治疗作用。ObjectiveTo investigate the effect of Cangfu Daotan Decoction on phlegm-damp typed rat model of polycystic ovary syndrome(PCOS)based on TLR-4/NF-κB signaling pathway.MethodsFifty female SD rats were randomly divided into blank group, model group and Chinese medicine(Cangfu Daotan Decoction) low-dose,medium-dose and high-dose groups(3.12,6.24,12.48 g·kg^(-1)). The rat model of phlegm-damp typed PCOS was established by Poresky modeling method combined with high fat diet. The model was successfully constructed,and intragastric administration of corresponding dose of Cangfu Daotan Decoction was given once a day,for 28 consecutive days. The pathological morphology of the ovarian tissues of rats was observed by Hematoxylin-eosin(HE)staining^(-1)The levels of interleukin-6(IL-6), tumor necrosis factorα(TNF-α), C-reactive protein(CRP) and other inflammatory factors in serum were determined by ELISA. The mRNA expressions of nuclear factor κB(NF-κB),Toll-like receptor 4(TLR-4) and oxidized low-density lipoprotein(ox-LDL) in ovarian tissues were detected by qRT-PCR;The expression of high mobility group protein 1(HMGB1) in ovarian tissues was detected by Immunohistochemistry.ResultsCompared with blank group, the quantity of mature ovarian follicles and corpus luteum in model group were significantly decreased(P < 0.05);Serum IL-6, TNF-α and CRP levels were significantly increased(P<0.05);The mRNA expressions of NF-κB, TLR-4 and ox-LDL in nest tissue were significantly up-regulated(P<0.05);The protein expression of HMGB1 in ovarian tissue was significantly upregulated(P<0.05). Compared with model group,the quantity of mature ovarian follicles and corpus luteum of ovary in medium-and high-dose groups were significantly increased(P<0.05);The levels of IL-6,TNF-α and CRP in serum were significantly decreased(P<0.05);The mRNA expression of NF-κB, ox-LDL, TLR-4 and protein HMGB1 in ovarian tissues were significantly down-regulated(P<0.05).Conclusion Cangfu DaotanDecoction may exert its therapeutic effects on PCOS by down

关 键 词：苍附导痰汤 多囊卵巢综合征 大鼠 TLR-4/NF-κB信号通路 炎性因子 

分 类 号：R285.5[医药卫生—中药学]