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1.河南中医药大学医学院,郑州 450046
2.河南中医药大学第三附属医院妇产科,郑州 450008
3.河南中医药大学临床技能实训中心,郑州 450046
高级实验师,硕士。研究方向:基础药理学。E-mail:zhangminghao@hactcm.edu.cn
副教授,硕士。研究方向:中医妇科学。电话:0371-86550201。E-mail:mary868@163.com
收稿日期:2022-04-15,
修回日期:2022-09-22,
纸质出版日期:2022-11-15
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张明昊,高一盈,董文霞,等.补肾强身片对多囊卵巢综合征模型大鼠的干预作用及机制研究[J].中国药房,2022,33(21):2632-2637.
ZHANG Minghao,GAO Yiying,DONG Wenxia,et al.Study on intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome model rats and its mechanism[J].ZHONGGUO YAOFANG,2022,33(21):2632-2637.
张明昊,高一盈,董文霞,等.补肾强身片对多囊卵巢综合征模型大鼠的干预作用及机制研究[J].中国药房,2022,33(21):2632-2637. DOI: 10.6039/j.issn.1001-0408.2022.21.13.
ZHANG Minghao,GAO Yiying,DONG Wenxia,et al.Study on intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome model rats and its mechanism[J].ZHONGGUO YAOFANG,2022,33(21):2632-2637. DOI: 10.6039/j.issn.1001-0408.2022.21.13.
目的
2
研究补肾强身片对多囊卵巢综合征(PCOS)模型大鼠的干预作用及机制。
方法
2
将50只大鼠灌胃来曲唑混悬液(1 mg/kg,每天1次,连续21 d)复制PCOS模型。将造模成功的大鼠分为模型组、阳性对照组(炔雌醇环丙孕酮片0.2 mg/kg+盐酸二甲双胍片230 mg/kg)和补肾强身片低、中、高剂量组(189、378、756 mg/kg),每组10只。另取10只未造模大鼠作为正常组。各组大鼠给予相应药物干预,每天1次,连续30 d。末次给药24 h后,检测大鼠血清中雌二醇(E
2
)、睾酮(T)、促性腺激素释放激素(GnRH)、促卵泡激素(FSH)和促黄体生成素(LH)水平,计算大鼠卵巢系数,观察大鼠卵巢组织病理形态学变化,检测大鼠卵巢组织中磷脂酰肌醇3激酶(PI3K)、磷酸化蛋白激酶B(p-Akt)、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)和葡萄糖转运蛋白4(GLUT4)的表达水平以及PI3K、Akt、mTOR、GLUT4 mRNA表达水平。
结果
2
与正常组比较,模型组大鼠卵巢系数、卵巢囊性病变评分均显著增加(
P
<0.05),血清中T、GnRH、LH水平均显著升高(
P
<0.05),血清中FSH、E
2
水平和卵巢组织中PI3K、p-Akt、p-mTOR、GLUT4蛋白表达水平及PI3K、Akt、mTOR、GLUT4 mRNA表达水平均显著降低(
P
<0.05),卵巢组织中闭锁卵泡及无卵丘的囊性卵泡数量增多,卵泡颗粒细胞层数减少。与模型组比较,补肾强身片中、高剂量组大鼠上述指标水平均显著逆转(
P
<0.05),低剂量组上述大部分指标水平显著逆转(
P
<0.05),卵巢组织病变均不同程度改善。
结论
2
补肾强身片可调节PCOS模型大鼠性激素分泌水平,改善卵巢囊性病变,其作用机制可能与上调PI3K/Akt/mTOR、PI3K/Akt/GLUT4两条信号通路有关。
OBJECTIVE
2
To study the intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome (PCOS) model rats and its mechanism.
METHODS
2
Totally 50 rats were given letrozole suspension (1 mg/kg, once a day, for consecutive 21 d) instragastrically to induce PCOS model. Model rars were randomly divided into model group, positive control group (Ethinylestradiol and cyproterone acetate tables 0.2 mg/kg+Metformin hydrochloride tables 230 mg/kg), Bushen qiangshen tablet low-dose, medium-dose a
nd high-dose groups (189, 378, 756 mg/kg), with 10 rats in each group. Another 10 healthy rats were included in normal group. Each group was given the corresponding drugs, once a day, for consecutive 30 d. Twenty-four hours after the last administration, serum levels of estrogen (E
2
), testosterone (T), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The ovary index was calculated, and pathological changes of ovary were observed. The protein expressions of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and glucose transporter 4 (GLUT4) in ovary were detected, and mRNA expressions of PI3K, Akt, mTOR and GLUT4 in ovary were detected.
RESULTS
2
Compared with normal group, ovarian index and ovarian cystic disease score were significantly increased in model group (
P
<0.05), and serum levels of T, GnRH and LH were significantly increased (
P
<0.05); serum levels of FSH and E
2
, protein expressions of PI3K, p-Akt, p-mTOR and GLUT4, and mRNA expression of PI3K, AKT, mTOR and GLUT4 in ovarian tissue were all significantly decreased in the model group (
P
<0.05); in ovarian tissue, the number of atresia follicles and non-cumulus cystic follicles increased, and the number of granulosa cell layers decreased. Compared with model group, above indexes of Bushen qiangshen tablet medium-dose and high-dose groups were reversed significantly (
P
<0.05), and most above indexes of low-dose group were reversed significantly (
P
<0.05), the pathological changes of ovarian tissue were improved to varying degrees.
CONCLUSIONS
2
Bushen qiangshen tablet can regulate the secretion of sex hormones in PCOS model rats and improve ovarian cystic lesions. Its mechanism may be related to the upregulation of PI3K/Akt/mTOR and PI3K/Akt/GLUT4 signaling pathways.
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