溴隐停、罗格列酮和二甲双胍对改善多囊卵巢综合征(PCOS)大鼠胰岛素抵抗和下调促炎细胞因子及调血脂作用研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (4): 391-396.

溴隐停、罗格列酮和二甲双胍对改善多囊卵巢综合征(PCOS)大鼠胰岛素抵抗和下调促炎细胞因子及调血脂作用研究

林佳¹, 刘广南², 潘竞锵², 邝少松³, 黄小琼³, 饶子亮³

¹广州市中医医院,广州510130,广东;
²广州市中医中药研究所,广州 510180,广东;
³广东省医学实验动物中心,佛山 528248,广东

收稿日期:2010-02-01 修回日期:2010-03-30 发布日期:2020-09-17
通讯作者: 潘竞锵,男,主任药师,从事抗炎-免疫、老年药学和生化药理学研究。 E-mail:pjq56@yahoo.com.cn
作者简介:林佳,女,副主任药师,从事药学以及实验药理学研究。E-mail: myemail008@21cn.com
基金资助:
广州市中医药、中西医结合项目(2004A055)

Effects of bromocriptine, rosiglitazone and metformin on insulin resistance downregulating proinflammatory cytokines and metabolism of lipids in rats with polycystic ovary syndrome

LIN Jia¹, LIU Guang-nan², PAN Jing-qiang², KUANG Shao-song³, HUANG Xiao-qiong³, RAO Zi-liang³

¹Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130,Guangdong, China;
²Guangzhou Institute of Traditional Chinese Medicine and Materia Medica, Guangzhou 510130, Guangdong,China;
³Guangdong Medical Experimental Animal Center, Foshan 528248, Guangdong, China

Received:2010-02-01 Revised:2010-03-30 Published:2020-09-17

摘要/Abstract

摘要： 目的: 观察溴隐停、二甲双胍、罗格列酮分别对多囊卵巢综合征(polycystic ovary syndrome ,PCOS)大鼠胰岛素抵抗、促炎细胞因子和脂肪细胞因子及血脂的干预作用。方法: 采用十一酸睾酮加绒促性素(human chorionic gonadotropin,HCG)建立PCOS大鼠模型,连续口服给予溴隐停、二甲双胍、罗格列酮6周,观察大鼠空腹血糖(fasting blood-glucose ,FBG)、口服葡萄糖后2小时血糖(OGTT-2 h BG)、胰岛素(insulin,Ins)、血清TC、TG、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、TNF-α、睾酮(testosterone,T)、胰岛素样生长因子(insulin growth factor-1,IGF-I)、高敏C反应蛋白(high sensitivity C-reactive protein ,hs-CRP)、瘦素(leptin, L)、脂联素(adiponectin, A)、抵抗素(resistin, R)等的含量,并计算胰岛素敏感指数(insulin sensitivity index, ISI)的变化。结果: PCOS大鼠FBG、OGTT-2hBG、 Ins、hs-CRP、TNF-α、 leptin、 resistin、 IGF-I、TC、TG、LDL-C和T水平明显升高,而ISI和adiponectin、HDL-C含量显著降低,与空白对照组比较,差异有统计学意义(P＜0.01);溴隐停、二甲双胍、罗格列酮均能不同程度地改善PCOS大鼠的上述病理改变(P<0.01～0.05)。结论: 溴隐停、二甲双胍、罗格列酮均能不同程度地改善PCOS大鼠胰岛素抵抗(IR)、高胰岛素血症、高雄激素血症和血糖、血脂代谢异常,以及下调促炎细胞因子和脂肪细胞因子。

关键词: 溴隐停, 二甲双胍, 罗格列酮, 多囊卵巢综合征, 胰岛素抵抗, 血脂, 促炎细胞因子

Abstract: AIM: To investigate effects of bromocriptine, rosiglitazone and metformin on insulin resistance (IR), proinflammatory cytokines, adipocytokines, blood glucose and lipid components in rats with polycystic ovary syndrome (PCOS). METHODS: The PCOS rats were molded by testosterone undecanoate and human chorionic gonadotropin (HCG), afterwards the rats were randomly divided into 4 groups: PCOS mold, bromocriptine, rosiglitazone and metformin; then all drugs were adiministered respectively by intragastric administration (i.g.) qd for 6 weeks. At the end of the experiment, the contents of fasting blood-glucose (FBG), 2-hours blood glucose after oral glucose tolerance test(OGTT-2 h BG), insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor (TNF-α),testosterone (T), insulin growth factor-1 (IGF-1), high sensitivity C-reactive protein(hs-CRP), leptin(L), adiponectin(A), resistin(R) were determined, and the changes of insulin sensitivity index (ISI) was counted. RESULTS: Compared with the normal group, concentrations of FBG, OGTT-2 h BG, Ins, hs-CRP, TNF-α, leptin, resistin, IGF-I, TC, TG, LDL-C and T were increased obviously(P<0.01), but ISI, adiponectin and HDL-C were decreased significantly (P<0.01) in PCOS rats. Bromocriptine, rosiglitazone and metformin could improve the pathologic changes in PCOS rats (P<0.01 or P<0.05). CONCLUSION: Bromocriptine, rosiglitazone and metformin can improve IR, hyperinsulinemia, hyperandrogenemia reduce blood glucose, adjust components of blood lipid, downregulate proinflammatory cytokines and regulate adipocytokines in PCOS rats.

Key words: Bromocriptine, Rosiglitazone, Metformin, Polycystic ovary syndrome, Insulin resistance, Blood lipid, Proinflammatory cytokines

中图分类号:

R965.2

林佳, 刘广南, 潘竞锵, 邝少松, 黄小琼, 饶子亮. 溴隐停、罗格列酮和二甲双胍对改善多囊卵巢综合征(PCOS)大鼠胰岛素抵抗和下调促炎细胞因子及调血脂作用研究[J]. 中国临床药理学与治疗学, 2010, 15(4): 391-396.

LIN Jia, LIU Guang-nan, PAN Jing-qiang, KUANG Shao-song, HUANG Xiao-qiong, RAO Zi-liang. Effects of bromocriptine, rosiglitazone and metformin on insulin resistance downregulating proinflammatory cytokines and metabolism of lipids in rats with polycystic ovary syndrome[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(4): 391-396.

参考文献

[1] Samy N, Hashim M, Sayed M, et al. Clinical significance of inflammatory markers in polycystic ovary syndrome: their relationship to insulin resistance and body mass index[J].Dis Markers, 2009,26(4):163-170.
[2] Kassi E, Diamanti-Kandarakis E. The effects of insulin sensitizers on the cardiovascular risk factors in women with polycystic ovary syndrome[J]. J Endocrinol Invest, 2008,31(12):1124-1131.
[3] 刘艳红,王霞,王爱华.二甲双胍联合达英-35在多囊卵巢综合征促排卵疗效的影响[J]. 中国妇幼保健, 2008,23:1266-1268.
[4] 陶建英,徐惠民.罗格列酮治疗多囊卵巢综合征胰岛素抵抗临床研究[J].中国现代医药杂志, 2008,10(3):45-47.
[5] 李冰,蒋亚玲,刘明星,等.溴隐亭治疗难治性多囊卵巢综合征不育的临床观察[J]. 生殖医学杂志, 2007,16(6):430-431.
[6] Sun F, Yu J. The effect of a special herbal tea on obesity and anovulation in androgen-sterilized rats[J]. Proc Soc Exp Biol Med, 2000,223(3):295-301.
[7] 冯瑞儿,潘竞锵,刘广南,等.益肾I方对多囊卵巢综合征-代谢综合征大鼠拮抗胰岛素抵抗抑制氧化应激及调血脂作用[J]. 中国药物与临床, 2009,8(11):1047-1051.
[8] 郑琳颖,潘竞锵,吕俊华.白芍总苷对脂肪肝大鼠增强胰岛素敏感性及抗脂肪肝作用[J]. 中国中药杂志, 2008,33(20):2385-2390.
[9] Luque-Ramírez M, Alvarez-Blasco F, Escobar-Morreale HF. Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients[J]. Obesity (Silver Spring), 2009,17(1):3-9.
[10] 刘广南,邝少松,潘竞锵,等.益肾Ⅰ方对PCOS大鼠胰岛素抵抗及血糖、血脂的影响[J]. 中医药临床杂志, 2009,21(3):189-191.
[11] González F, Rote NS, Minium J, et al. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2006,91(1):336-340.
[12] Delfino FJ, Boustead JN, Fix C, et al. NF-κB and TNF-α stimulate androgen receptor expression in Sertoli cells[J]. Mol Cell Endocrinol, 2003,201(1/2):1-12.
[13] Diamanti-Kandarakis E, Xyrafis X, Boutzios G, et al. Pancreatic β-cells dysfunction in polycystic ovary syndrome[J]. Panminerva Med, 2008,50(4):315-325.
[14] 王培,顾林.多囊卵巢代谢异常的研究进展[J]. 国外医学妇幼保健分册, 2005,16(3):309.
[15] 陈金仲,邵豪.脂代谢紊乱与胰岛素抵抗的相关研究进展[J]. 中国实用医药, 2008,3(3):147-148.
[16] Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance[J]. Mol Med, 2008,14(3/4):222-231.
[17] Apovian CM, Bigornia S, Mott M, et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects[J]. Arterioscler Thromb Vasc Biol, 2008, 28(9): 1654-1659.
[18] Elloumi M, Ben Ounis O, Makni E, et al. Effect of individualized weight-loss programmes on adiponectin, leptin and resistin levels in obese adolescent boys[J]. Acta Paediatr, 2009,1.
[19] Marciniak A, Starczewski A. The role of leptin in polycystic ovary syndrome[J]. Pol Merkur Lekarski, 2008,25(148):390-393.
[20] 田俊华,田秀珠,马淑状,等.IGF-Ⅰ和TGF-β1在多囊卵巢综合征大鼠卵巢中的表达及意义[J].山西医科大学学报, 2009,40(08):700-703,768.
[21] 彭弋峰,彭守静,俞丽华,等.溴隐亭干预对男性高催乳素血症伴阳痿患者血清催乳素水平的影响[J]. 中国临床药理学与治疗学, 2000,5(1):73-74.
[22] Hashimoto S, Yatabe J, Midorikawa S, et al. Inhibition of growth hormone excess reduces insulin resistance and ovarian dysfunction in a lean case of polycystic ovary syndrome with a growth-hormone-producing pituitary adenoma[J]. Horm Res, 2003,59(3):149-155.
[23] Scranton RE, Gaziano JM, Rutty D, et al. A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset or placebo[J]. BMC Endocr Disord, 2007,7:3.
[24] Svendsen PF, Nilas L, Madsbad S, et al. Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin[J]. Metabolism, 2009,58(5):586-593.
[25] Mathur R, Alexander CJ, Yano J, et al .Use of metformin in polycystic ovary syndrome[J]. Am J Obstet Gynecol, 2008,199(6):596-609.
[26] Tsilchorozidou T, Mohamed-Ali V, Conway GS. Determinants of interleukin-6 and C-reactive protein vary in polycystic dvary syndrome, as do effects of short-and long-term metformin therapy[J]. Horm Res, 2009,71(3):148-154.
[27] Radosh L. Drug treatments for polycystic ovary syndrome[J]. Am Fam Physician, 2009,79(8):671-676.
[28] Majuri A, Santaniemi M, Rautio K, et al. Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study[J]. Eur J Endocrinol, 2007,156(2):263-269.