荷芪散对多囊卵巢综合征模型大鼠内分泌代谢的影响及PI3K/AKT信号通路的调控作用
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摘要
目的:分析荷芪散对多囊卵巢综合征模型大鼠内分泌代谢的影响和PI3K/AKT信号通路的调控作用。方法:80只大鼠随机分成正常组、模型组、荷芪散组以及二甲双胍组。比较4组大鼠空腹血糖(fasting plasma glucose,FPG)、总胆固醇(total cholesterol,TC)、三酰甘油(triacylglycerol,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoproteincholesterol,HDL-C)、空腹胰岛素(fasting insulin,FINS)、黄体生成素(luteinizing hormone,LH)、促卵泡激素(follicle-stimulating hormone,FSH)及睾丸素(testosterone,T)水平,卵巢组织情况以及卵巢组织中的IRS-1、AKT-2、CSK-3β、GLUT-4以及PTEN mRNA相对表达量。结果:模型组FPG、FINS、HOMA-IR、TC、TG、LDL-C水平均高于荷芪散组和二甲双胍组(P <0. 05);荷芪散组TC水平高于二甲双胍组,两组比较,差异有统计学意义(P <0. 05);荷芪散组TG、LDL-C水平均显著低于二甲双胍组(P <0. 05)。荷芪散组、二甲双胍组LH、T水平均显著高于正常组(P <0. 05);荷芪散组LH水平显著低于二甲双胍组(P <0. 05),FSH水平显著高于二甲双胍组(P <0. 05)。与模型组比较,荷芪散组和二甲双胍组卵巢组织均显著改善。荷芪散组、二甲双胍组IRS-1、AKT-2、CSK-3β、GLUT-4 mRNA表达量均显著高于正常组(P <0. 05),而PTEN mRNA表达显著低于模型组(P <0. 05);荷芪散组IRS-1、AKT-2、CSK-3β、GLUT-4mRNA表达量均显著高于二甲双胍组(P <0. 05),而荷芪散组PTEN mRNA表达量显著低于二甲双胍组(P <0. 05)。结论:荷芪散通过作用于PI3K/AKT信号通路的相关因子,上调IRS-1、AKT-2、CSK-3β、GLUT-4等基因表达,改善大鼠的糖代谢,降低胰岛素水平和调整激素紊乱状态。
Objective: To analyze the effect of Heqi powder on endocrine metabolism and the regulation of PI3K/AKT signaling pathway in polycystic ovary syndrome model rats. Methods: 80 rats were randomly divided into normal group,model group,Heqi powder group and metformin group. The level of fasting plasma glucose( FPG),total cholesterol( TC),triacylglycerol( TG),lowdensity lipoprotein cholesterol( LDL-C),high density lipoproteincholesterol( HDL-C),fasting insulin( FINS),luteinizing hormone( LH),follicle stimulating hormone( FSH),testosterone( T),ovarian tissue condition and relative expression of IRS-1,AKT-2,CSK-3β,GLUT-4 and PTEN mRNA in ovarian tissue were compared in four groups. Results: The levels of FPG,FINS,HOMA-IR,TC,TG and LDL-C in model group were higher than those in Heqi powder group and metformin group( P < 0. 05); the TC level in Heqi powder group was higher than that in metformin group,and the difference between the two groups was statistically significant( P < 0. 05); the levels of TG and LDL-C in Heqi powder group were significantly lower than that in metformin group( P < 0. 05). The levels of LH and T in Heqi powder group and metformin group were significantly higher than those in normal group( P < 0. 05); the level of LH in Heqi powder group was significantly lower than that in metformin group( P < 0. 05),and the level of FSH in Heqi powder group was significantly higher than that in metformin group( P < 0. 05). Compared with the model group,the ovarian tissue of Heqi powder group and metformin group were significantly improved. The expressions of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA in Heqi powder group and metformin group were significantly higher than those in normal group( P < 0. 05),while the expression of PTEN mRNA was significantly lower than that in model group( P < 0. 05). The expressions of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA in Heqi powder group were significantly higher than those in metformin group( P <0. 05),while the expression of PTEN mRNA in Heqi powder group was significantly lower than that in metformin group( P <0. 05). Conclusion: Heqi Powder can up-regulate the expression of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA by acting on the related factors of PI3K/AKT signaling pathway,improve the glucose metabolism,reduce insulin level and regulate hormone disorder in rats.
Objective: To analyze the effect of Heqi powder on endocrine metabolism and the regulation of PI3K/AKT signaling pathway in polycystic ovary syndrome model rats. Methods: 80 rats were randomly divided into normal group,model group,Heqi powder group and metformin group. The level of fasting plasma glucose( FPG),total cholesterol( TC),triacylglycerol( TG),lowdensity lipoprotein cholesterol( LDL-C),high density lipoproteincholesterol( HDL-C),fasting insulin( FINS),luteinizing hormone( LH),follicle stimulating hormone( FSH),testosterone( T),ovarian tissue condition and relative expression of IRS-1,AKT-2,CSK-3β,GLUT-4 and PTEN mRNA in ovarian tissue were compared in four groups. Results: The levels of FPG,FINS,HOMA-IR,TC,TG and LDL-C in model group were higher than those in Heqi powder group and metformin group( P < 0. 05); the TC level in Heqi powder group was higher than that in metformin group,and the difference between the two groups was statistically significant( P < 0. 05); the levels of TG and LDL-C in Heqi powder group were significantly lower than that in metformin group( P < 0. 05). The levels of LH and T in Heqi powder group and metformin group were significantly higher than those in normal group( P < 0. 05); the level of LH in Heqi powder group was significantly lower than that in metformin group( P < 0. 05),and the level of FSH in Heqi powder group was significantly higher than that in metformin group( P < 0. 05). Compared with the model group,the ovarian tissue of Heqi powder group and metformin group were significantly improved. The expressions of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA in Heqi powder group and metformin group were significantly higher than those in normal group( P < 0. 05),while the expression of PTEN mRNA was significantly lower than that in model group( P < 0. 05). The expressions of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA in Heqi powder group were significantly higher than those in metformin group( P <0. 05),while the expression of PTEN mRNA in Heqi powder group was significantly lower than that in metformin group( P <0. 05). Conclusion: Heqi Powder can up-regulate the expression of IRS-1,AKT-2,CSK-3β and GLUT-4 mRNA by acting on the related factors of PI3K/AKT signaling pathway,improve the glucose metabolism,reduce insulin level and regulate hormone disorder in rats.
引文
[1]DI PIETRO M,PASCUALI N,PARBORELL F,et al.Ovarian angiogenesis in polycystic ovary syndrome[J].Reproduction,2018,155(5):R199-R209.
[2]方如丹,舒荣梅.加味逍遥散合克罗米芬治疗多囊卵巢综合征30例[J].中医杂志,2011,52(22):1957-1959.
[3]崔琳琳,陈子江.多囊卵巢综合征的临床分型及意义[J].中华妇产科杂志,2010,45(8):623-625.
[4]邓选碧.多囊卵巢综合征的两种治疗方法的对比及其中医施治[J].时珍国医国药,2012,23(11):2918-2919.
[5]郝薇,郭影,郝桂敏,等.miRNA与多囊卵巢综合征发病机制相关性的研究进展[J].生殖医学杂志,2016,25(12):1126-1129.
[6]李红芬,郑肇巽,马品耀,等.HE染色原理和试剂配制及染色过程中的若干问题的探讨[J].医学信息,2011,24(4):1985-1986.
[7]FIENBERG R.Thecosis:a study of diffuse stromal thecosis of the ovary and superficial collagenization with follicular cysts[J].Obstet Gynecol,1963,21(6):687-700.
[8]刘文.中西医结合治疗多囊卵巢综合征不孕症20例[J].中国中医药现代远程教育,2012,10(14):50-51.
[9]李亚茜,俞超芹,翟东霞,等.基于文献多囊卵巢综合征中医证候规律研究初探[J].中国中医基础医学杂志,2015,21(9):1081-1082.
[10]吴霍曼,李兆萍,王蕴琪,等.调经汤对多囊卵巢综合征不孕卵泡质量和激素分泌的影响[J].中国实验方剂学杂志,2014,20(18):200-203.
[11]魏美娟,俞瑾.天癸方治疗高雄激素无排卵症临床观察[J].中华内分泌代谢杂志,2001,17(2):105-106.
[12]曹云霞,唐静文.多囊卵巢综合征患者胰岛素抵抗和高胰岛素血症的诊治[J].中国实用妇科与产科杂志,2013,29(11):864-866.
[13]何珲,姜冬梅,康波,等.哺乳动物卵巢卵泡膜细胞功能的研究进展[J].畜牧兽医学报,2013,44(9):1337-1341.
[14]罗莉,陈晓菁,吴建波,等.多囊卵巢综合征患者内脂素水平对卵巢胰岛素信号转导影响[J].中国公共卫生,2013,29(12):1790-1792.
[15]刘洋,田见晖,王淑敏,等.Notch信号通路与哺乳动物卵泡发育的研究进展[J].黑龙江畜牧兽医,2015,46(21):79-82.
[16]迟毓婧,李晶,管又飞,等.PI3K-Akt信号传导通路对糖代谢的调控作用[J].中国生物化学与分子生物学报,2010,26(10):879-885.
[17]马曼华,王旭东.调肾清肺法治疗多囊卵巢综合征高雄激素血症26例[J].南京中医药大学学报,2010,26(4):311-312.
[2]方如丹,舒荣梅.加味逍遥散合克罗米芬治疗多囊卵巢综合征30例[J].中医杂志,2011,52(22):1957-1959.
[3]崔琳琳,陈子江.多囊卵巢综合征的临床分型及意义[J].中华妇产科杂志,2010,45(8):623-625.
[4]邓选碧.多囊卵巢综合征的两种治疗方法的对比及其中医施治[J].时珍国医国药,2012,23(11):2918-2919.
[5]郝薇,郭影,郝桂敏,等.miRNA与多囊卵巢综合征发病机制相关性的研究进展[J].生殖医学杂志,2016,25(12):1126-1129.
[6]李红芬,郑肇巽,马品耀,等.HE染色原理和试剂配制及染色过程中的若干问题的探讨[J].医学信息,2011,24(4):1985-1986.
[7]FIENBERG R.Thecosis:a study of diffuse stromal thecosis of the ovary and superficial collagenization with follicular cysts[J].Obstet Gynecol,1963,21(6):687-700.
[8]刘文.中西医结合治疗多囊卵巢综合征不孕症20例[J].中国中医药现代远程教育,2012,10(14):50-51.
[9]李亚茜,俞超芹,翟东霞,等.基于文献多囊卵巢综合征中医证候规律研究初探[J].中国中医基础医学杂志,2015,21(9):1081-1082.
[10]吴霍曼,李兆萍,王蕴琪,等.调经汤对多囊卵巢综合征不孕卵泡质量和激素分泌的影响[J].中国实验方剂学杂志,2014,20(18):200-203.
[11]魏美娟,俞瑾.天癸方治疗高雄激素无排卵症临床观察[J].中华内分泌代谢杂志,2001,17(2):105-106.
[12]曹云霞,唐静文.多囊卵巢综合征患者胰岛素抵抗和高胰岛素血症的诊治[J].中国实用妇科与产科杂志,2013,29(11):864-866.
[13]何珲,姜冬梅,康波,等.哺乳动物卵巢卵泡膜细胞功能的研究进展[J].畜牧兽医学报,2013,44(9):1337-1341.
[14]罗莉,陈晓菁,吴建波,等.多囊卵巢综合征患者内脂素水平对卵巢胰岛素信号转导影响[J].中国公共卫生,2013,29(12):1790-1792.
[15]刘洋,田见晖,王淑敏,等.Notch信号通路与哺乳动物卵泡发育的研究进展[J].黑龙江畜牧兽医,2015,46(21):79-82.
[16]迟毓婧,李晶,管又飞,等.PI3K-Akt信号传导通路对糖代谢的调控作用[J].中国生物化学与分子生物学报,2010,26(10):879-885.
[17]马曼华,王旭东.调肾清肺法治疗多囊卵巢综合征高雄激素血症26例[J].南京中医药大学学报,2010,26(4):311-312.