摘要
目的研究茯苓酸对多囊卵巢综合征(PCOS)大鼠胰岛素抵抗的改善作用及机制。方法将126只雌性大鼠按随机数字表法分为空白组、PCOS组、茯苓酸低剂量组(8.33 mg/kg)、茯苓酸高剂量组(33.32 mg/kg)、炔雌醇环丙孕酮组(阳性对照组,0.34 mg/kg)、重组大鼠高迁移率族蛋白B1蛋白(rHMGB1)组(8μg/kg)和茯苓酸高剂量+rHMGB1组(33.32 mg/kg茯苓酸+8μg/kg rHMGB1),每组18只。除空白组外,其余各组大鼠均通过灌胃来曲唑混悬液的方式构建PCOS模型。建模成功后,每天给药1次,持续4周。给药结束后,检测大鼠空腹血糖、空腹胰岛素水平及胰岛素抵抗指数(HOMA-IR),检测大鼠血清中促卵泡素(FSH)、促黄体生成素(LH)、睾酮(T)水平及卵巢组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平,计算大鼠卵巢系数,观察大鼠卵巢组织病理变化,检测大鼠卵巢组织中HMGB1、晚期糖基化终产物受体(RAGE)、磷酸化核因子κB p65(p-NF-κB p65)蛋白表达情况。结果与空白组比较,PCOS组大鼠卵巢组织病理损伤严重,空腹血糖、空腹胰岛素水平、HOMA-IR、卵巢系数升高,血清中LH和T水平升高、FSH水平降低,卵巢组织中IL-1β、TNF-α水平及HMGB1、RAGE、p-NF-κB p65蛋白表达量升高,差异均具有统计学意义(P<0.05)。与PCOS组比较,茯苓酸低、高剂量组和炔雌醇环丙孕酮组大鼠卵巢组织病理损伤减轻,空腹血糖、空腹胰岛素水平、HOMA-IR、卵巢系数降低,血清中LH和T水平降低、FSH水平升高,卵巢组织中IL-1β、TNF-α水平及HMGB1、RAGE、p-NF-κB p65蛋白表达量降低,差异均具有统计学意义(P<0.05);rHMGB1组大鼠对应指标的变化趋势与上述给药组相反(P<0.05)。与茯苓酸高剂量组比较,茯苓酸高剂量+rHMGB1组大鼠的上述指标变化均被显著逆转(P<0.05)。结论茯苓酸可能通过抑制HMGB1/RAGE信号通路改善PCOS大鼠胰岛素抵抗并抑制其炎症反应。
OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome(PCOS)and its mechanism.METHODS One hundred and twenty-six female rats were randomly separated into blank group,PCOS group,poria acid low-dose group(8.33 mg/kg),pachymic acid high-dose group(33.32 mg/kg),ethinylestradiol cyproterone group(positive control group,0.34 mg/kg),recombinant rat high mobility group protein B1 protein(rHMGB1)group(8μg/kg),and poria acid high dose+rHMGB1 group(33.32 mg/kg poria acid+8μg/kg rHMGB1),with 18 rats in each group.Except for the blank group,the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model.After successful modeling,administration was performed once a day for 4 weeks.After medication,the fasting blood glucose and fasting insulin levels,and insulin resistance index(HOMA-IR)were measured in rats;the levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH)and testosterone(T)in rat serum,and the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in ovarian tissue were detected;ovarian coefficients of rats were calculated;the pathological changes of ovarian tissue were observed;the expressions of HMGB1,receptor for advanced glycosylation end product(RAGE)and phosphorylated nuclear factorκB p65(p-NF-κB p65)proteins were determined in ovarian tissue of rats.RESULTS Compared with the blank group,the pathological injury of ovarian tissue of rats in the PCOS group was serious,the levels of fasting blood glucose and fasting insulin,HOMA-IR and ovarian coefficient were increased,the levels of serum LH and T were increased,while the levels of FSH were decreased;the levels of IL-1βand TNF-α,the expressions of HMGB1,RAGE and p-NF-κB p65 protein in ovarian tissue were increased,with statistical significance(P<0.05).Compared with the PCOS group,pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group,and fasting blood glucose,fasting insulin levels,HOMA-IR and ovarian coefficient were decreased;serum LH and T levels were decreased,while FSH levels were increased;the levels of IL-1βand TNF-αand the expressions of HMGB1,RAGE and p-NF-κB p65 protein in ovarian tissue were decreased,with statistical significance(P<0.05).The trend of corresponding indexes in rHMGB1 group was opposite to the above(P<0.05).Compared with poria acid high-dose group,the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group(P<0.05).CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/RAGE pathway.
作者
唐虹
李林霞
华宇
蒋晓梅
章仕雯
付金荣
TANG Hong;LI Linxia;HUA Yu;JIANG Xiaomei;ZHANG Shiwen;FU Jinrong(Dept.of Gynecology,Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Dept.of Obstetrics and Gynecology,the Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China)
出处
《中国药房》
CAS
北大核心
2024年第1期57-62,共6页
China Pharmacy
基金
全国中医学术流派传承工作室第二轮建设项目(No.国中医药人教函〔2019〕62号)
上海市浦东新区科技发展基金事业单位民生科研专项(医疗卫生项目)(No.PKJ2022-Y09)
上海市第七人民医院“名中医继承人”人才培养计划项目(No.JCR2021-02)。
作者简介
第一作者:唐虹,主治医师,博士研究生。研究方向:中西医结合治疗女性月经不调、不孕症、多囊卵巢综合征、痛经等。E-mail:elaine_tanghong@sina.com;通信作者:付金荣,主任医师,博士。研究方向:中西医结合治疗妇科疑难疾病、多囊卵巢综合征、子宫内膜异位症、慢性盆腔炎、不孕症、痛经等。E-mail:fujinrong2006@sina.com。
