首页|基于SIRT1/PGC-1α/Cyt C通路探讨养精种玉汤联合寿胎丸对PCOS-IR大鼠的影响

基于SIRT1/PGC-1α/Cyt C通路探讨养精种玉汤联合寿胎丸对PCOS-IR大鼠的影响

扫码查看
目的 基于沉默信息调节因子2相关酶1(SIRT1)/过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1 α)/细胞色素C(Cyt C)通路探究养精种玉汤联合寿胎丸对多囊卵巢综合征合并胰岛素抵抗(PCOS-IR)大鼠的影响.方法 取雌性SD大鼠110只,随机选取97只大鼠,以皮下注射脱氢表雄酮及高脂饲料喂养方法建立PCOS-IR模型,其余大鼠作为正常组.将造模成功后大鼠随机分为8组,每组12只.二甲双胍组给予0.265 g/kg二甲双胍灌胃,寿胎丸组给予12 g/kg寿胎丸灌胃,低剂量养精种玉汤组给予33 g/kg养精种玉汤灌胃,高剂量养精种玉汤组给予66 g/kg养精种玉汤灌胃,低剂量养精种玉汤+寿胎丸组给予33 g/kg养精种玉汤+12 g/kg寿胎丸灌胃,高剂量养精种玉汤+寿胎丸组给予66 g/kg养精种玉汤+12 g/kg寿胎丸灌胃,高剂量养精种玉汤+寿胎丸+EX-527组给予66 g/kg养精种玉汤+12 g/kg寿胎丸灌胃和5 mg/kg EX-527腹腔注射,正常组和模型组给予生理盐水灌胃与腹腔注射,均1次/d,连续干预14d.记录大鼠的体重;血糖仪、ELISA试剂盒分别检测大鼠的空腹血糖(FPG)和空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR)和血糖曲线下面积(GAUC);ELISA法检测大鼠血清黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)、雌二醇(E2)水平;HE染色观察大鼠卵巢组织病理学形态;Western blot法检测大鼠卵巢组织中SIRT1/PGC-1α/Cyt C信号通路相关蛋白表达情况.结果 与正常组比较,模型组大鼠FPG、GAUC、HOMA-IR、LH、T水平及卵巢组织中Cyt C蛋白相对表达量均明显升高(P均<0.05),FSH、E2水平及卵巢组织中SIRT1、PGC-1α蛋白相对表达量均明显降低(P均<0.05);大鼠卵巢组织呈多囊样病变,囊性扩张卵泡增多,卵泡体积增大,颗粒细胞排列疏松紊乱.与模型组比较,各药物组大鼠的体重下降程度较大(P均<0.05),FPG、GAUC、HOMA-IR、LH、T水平及卵巢组织中Cyt C蛋白相对表达量均明显降低(P均<0.05),FSH、E2水平及卵巢组织中SIRT1、PGC-1α蛋白相对表达量均明显升高(P均<0.05),大鼠卵巢组织多囊样病变减轻;高剂量养精种玉汤+寿胎丸组上述各项指标及卵巢组织多囊样病变改善更明显,而EX-527减弱了高剂量养精种玉汤联合寿胎丸对大鼠PCOS-IR进展的阻碍作用.结论 养精种玉汤联合寿胎丸可能通过调节SIRT1/PGC-1α/Cyt C信号通路改善PCOS-IR大鼠性激素水平,延缓PCOS-IR进展.
Effect of Yangjing Zhongyu decoction combined with Shoutai pill on PCOS-IR in rats based on SIRT1/PGC-1α/Cyt C pathway
Objective It is to investigate the effect of Yangjing Zhongyu decoction combined with Shoutai pill in the treatment of polycystic ovary syndrome complicated with insulin resistance(PCOS-IR)in rats based on the silent informa-tion regulation 2 homolog 1(SIRT1)/peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)/cytochrome C(Cyt C)pathway.Methods A total of 110 female SD rats were selected,in which 97 rats were randomly selected and given DHEA by subcutaneous injection and fed with high-fat diet to establish PCOS-IR models,and the other rats were taken as normal group.After successful modeling,the rats were randomly divided into 8 groups,with 12 rats in each group.The metformin group was given metformin 0.265 g/kg by gavage,the Shoutai pill group was given Shoutai pill 12 g/kg by ga-vage,the low-dose and high-dose groups of Yangjing Zhongyu decoction group was respectively given Yangjingzhongyu de-coction 33 g/kg and 66 g/kg by gavage,the low-dose Yangjing Zhongyu decoction+Shoutai pill group was given Yangjing Zhongyu decoction 33 g/kg and Shoutai pill 12 g/kg,the high-dose Yangjing Zhongyu decoction+Shoutai pill group was given Yangjing Zhongyu decoction 66 g/kg and Shoutai pill 12 g/kg by gavage,the high-dose Yangjing Zhongyu decoction+Shoutai pill+EX-527 group was given Yangjing Zhongyu decoction 66 g/kg,Shoutai pill 12 g/kg by gavage and EX-5275 mg/kg by intraperitoneal injection,the normal group and model group were given normal saline by intragastric injection and intraperitoneal injection,all once daily,continuously treated for 14 days.The body weights of the rats were recorded;the levels of fasting plasma glucose(FPG)and fasting insulin(FINS)of the rats were respectively determined by blood glucose meters and ELISA kits,and their insulin resistance index(HOMA-IR)and glucose area under the curve(GAUC)were calculated;the serum levels of luteinizing hormone(LH),follicle stimulating hormone(FSH),testosterone(T),and estradiol(E2)were determined by ELISA;the pathological changes in ovarian tissue were observed by HE staining;the expressions of SIRT1/PGC-1α/Cyt C signaling pathway related proteins in ovarian tissue were detected by Western Blot.Results Compared with the normal group,the levels of FPG,GAUC,HOMA-IR,LH,T in serum,and the relative expression of Cyt C protein in ovarian tissue of rats in the model group were obviously increased(all P<0.05),the levels of FSH and E2 in serum,and the relative expressions of SIRT1 and PGC-1α proteins in ovarian tissue were obviously re-duced(all P<0.05),there were polycystic lesions with increased cystic dilated follicles,increased follicular size,and loose and disorganized granulosa cell arrangement in the ovarian tissue of the rats.Compared with the model group,the weight loss of the rats of all treatment groups was obviously increased(all P<0.05),and the levels of FPG,GAUC,HO-MA-1R,LH,T in serum and relative expressions of Cyt C protein in ovarian tissue were significantly decreased(all P<0.05),the levels of FSH and E2 in serum and the relative expressions of SIRT1 and PGC-1α protein in ovarian tissue were significantly increased(all P<0.05),and the polycystic lesions of ovarian tissue in the rats were alleviated.The improve-ments of the above indexes and polycystic lesions of ovarian tissue were more obvious in the high-dose Yangjing Zhongyu Decoction+Shoutai pill group,while EX-527 weakened the inhibitory effect of Yangjing Zhongyu decoction combined with Shoutai pill on the progression of PCOS-IR in rats.Conclusion Yangjing Zhongyu decoction combined with Shoutai pill may improve sex hormone levels in PCOS-IR rats and delay the progression of PCOS-IR via regulating the SIRT1/PGC-1α/Cyt C signaling pathway.

polycystic ovary syndromeinsulin resistanceYangjing Zhongyu decoctionshoutai pillsilent mating type information regulation 2 homolog 1peroxisome proliferator-activated receptor γ coactivator-1αcytochrome C

聂春莹、马红霞、胡敏

展开 >

广西中医药大学研究生院,广西南宁 530001

广州医科大学附属第一医院,广东广州 510163

多囊卵巢综合征 胰岛素抵抗 养精种玉汤 寿胎丸 沉默信息调节因子2相关酶1 过氧化物酶体增殖活化受体γ辅助活化因子1α 细胞色素C

国家自然科学基金资助项目国家自然科学基金资助项目

8237450181973892

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(11)