文献类型：期刊文献

中文题名：基于PI3K/Akt/mTOR信号通路探讨左归丸对^(60)Co-γ射线损伤大鼠卵泡凋亡调控作用

英文题名：Protection of Zuoguiwan Against Apoptosis of Follicles in Rats Injured by ^(60)Co-γRays:Based on PI3K/Akt/mTOR Signaling Pathway

作者：赵粉琴[1];安明霞[1];丁晓南[1];刘洁颖[1];赵艳[1];谢知慧[1];李淑萍[2]

第一作者：赵粉琴

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃省人民医院,兰州730000

第一机构：甘肃中医药大学

年份：2022

卷号：28

期号：18

起止页码：12

中文期刊名：中国实验方剂学杂志

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(81760806);2019年甘肃省中医药管理局项目(GZK-2019-28);甘肃省教育厅甘肃省高等学校创新能力提升项目(2019B-103)。

语种：中文

中文关键词：辐射损伤;卵巢早衰(POF);左归丸;原位末端标记法(TUNEL);磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素的哺乳动物靶标(PI3K/Akt/mTOR)信号通路;B细胞淋巴瘤-2(Bcl-2);Bcl-2相关X蛋白(Bax)

外文关键词：radiation damage;premature ovarian failure(POF);Zuoguiwan;terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL);phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway;B-cell lymphoma-2;Bcl-2-associated X protein

摘要：目的以磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路为靶点,探讨左归丸对^(60)Co-γ射线早衰大鼠的保护作用。方法采用^(60)Co-γ射线一次性照射(6.0 Gy,LD_(40))性成熟雌性SD大鼠60只,随机分成模型组、补佳乐组(0.18 g·kg^(-1)·d^(-1))、补佳乐(0.09 g·kg^(-1)·d^(-1))+左归丸高剂量(23.625 g·kg^(-1)·d^(-1))组、左归丸高剂量(23.625 g·kg^(-1)·d^(-1))组、左归丸中剂量(9.45 g·kg^(-1)·d^(-1))组和左归丸低剂量(4.725 g·kg^(-1)·d^(-1))组,每日1次,治疗21 d,酶联免疫吸附测定法(ELISA)检测大鼠血清[卵泡刺激素(FSH)、黄体生成素(LH)和雌二醇(E_(2))],苏木素-伊红(HE)染色观察卵巢的组织形态变化,原位末端标记法(TUNEL)检测颗粒细胞凋亡率,蛋白免疫印迹法(Western blot)检测卵巢组织磷酸化(p)-PI3K、p-Akt、p-mTOR和B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的蛋白表达结果。结果与正常组比较,模型组大鼠血清FSH显著上升(P<0.01),E2明显下降(P<0.05),卵巢早期卵泡和黄体数量减少(P<0.01);颗粒细胞凋亡率显著增加(P<0.01);卵巢组织p-PI3K、p-Akt、p-mTOR和Bcl-2蛋白表达明显下降,Bax蛋白表达显著增加(P<0.01);与模型组比较,各给药组干预后卵巢内早期卵泡数量增加,颗粒细胞凋亡率降低,p-PI3K、p-Akt、p-mTOR和Bcl-2蛋白表达有增加趋势,Bax蛋白表达有下降趋势,尤以补佳乐+左归丸高剂量组差异均具有统计学意义(P<0.05,P<0.01)。结论左归丸对辐射损伤卵巢的保护作用机制可能是通过活化卵巢组织PI3K/Akt/mTOR蛋白表达,增加Bcl-2蛋白量和抑制Bax蛋白表达。
Objective To investigate the protective effect of Zuoguiwan against ^(60)Co-γray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway.Method Sixty sexually mature female SD rats were irradiated with ^(60)Co-γrays(6.0 Gy,LD_(40))for 24 h at one time.Then they were randomized into model group,Bujiale group(0.18 g·kg^(-1)·d^(-1)),Bujiale(0.09 g·kg^(-1)·d^(-1))+high-dose Zuoguiwan group(23.625 g·kg^(-1)·d^(-1)),high-dose Zuoguiwan group(23.625 g·kg^(-1)·d^(-1)),medium-dose Zuoguiwan group(9.45 g·kg^(-1)·d^(-1)),and low-dose Zuoguiwan group(4.725 g·kg^(-1)·d^(-1)).The administration(once a day)lasted 21 days.Serum indexes[follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E_(2))]of rats were detected by enzyme-linked immunosorbent assay(ELISA),and morphological changes of ovarian tissues were observed based on hematoxylin and eosin(HE)staining.The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)and the protein expression of phosphorylated(p)-PI3K,p-Akt,p-mTOR,B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)in ovarian tissues by Western blot.Result Compared with normal group,model group demonstrated increase in serum FSH(P<0.01),decrease in E2(P<0.05),and reduction of follicles and luteum in early ovary(P<0.01).Moreover,the elevation of apoptosis rate of granulosa cells(P<0.01),down-regulation of p-PI3K,p-Akt,p-mTOR,and Bcl-2 in ovarian tissue,and increase in expression of Bax were also observed in the model group as compared with the normal group(P<0.01).In comparison with the model group,the administration groups showed rise of the number of early ovarian follicles,decrease in the apoptosis rate of granulosa cells,increase in the expression of p-PI3K,p-Akt,p-mTOR,and Bcl-2,and down-regulation of Bax,particularly the Bujiale+high-dose Zuoguiwan group(P<0.05,P<0.01).Conclusion Zuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue,increasing Bcl-2,and inhibiting the expression of Bax.