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1.上海中医药大学附属龙华医院妇科,上海 200032
2.上海中医药大学附属第七人民医院妇产科,上海 200137
Published:15 January 2024,
Received:05 July 2023,
Revised:19 November 2023,
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唐虹,李林霞,华宇等.茯苓酸改善多囊卵巢综合征大鼠胰岛素抵抗的作用及机制研究 Δ[J].中国药房,2024,35(01):57-62.
TANG Hong,LI Linxia,HUA Yu,et al.Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism[J].ZHONGGUO YAOFANG,2024,35(01):57-62.
唐虹,李林霞,华宇等.茯苓酸改善多囊卵巢综合征大鼠胰岛素抵抗的作用及机制研究 Δ[J].中国药房,2024,35(01):57-62. DOI: 10.6039/j.issn.1001-0408.2024.01.10.
TANG Hong,LI Linxia,HUA Yu,et al.Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism[J].ZHONGGUO YAOFANG,2024,35(01):57-62. DOI: 10.6039/j.issn.1001-0408.2024.01.10.
目的
2
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
2
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(8 μg/kg)和茯苓酸高剂量+rHMGB1组(33.32 mg/kg茯苓酸+8 μg/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
2
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
2
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
2
To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome (PCOS) and its mechanism.
METHODS
2
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 (8 μg/kg), and poria acid high dose+rHMGB1 group (33.32 mg/kg poria acid+8 μg/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 factor κB p65 (p-NF-κB p65) proteins were determined in ovarian tissue of rats.
RESULTS
2
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-1β and 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-1β and TNF-α and 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
2
Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/RAGE pathway.
茯苓酸多囊卵巢综合征高迁移率族蛋白B1/晚期糖基化终产物受体通路胰岛素抵抗炎症反应
polycystic ovary syndromeHMGB1/RAGE pathwayinsulin resistanceinflammation response
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