肌肉肌醇与D-手性肌醇在多囊卵巢综合征中的研究及应用

doi:10.12280/gjszjk.20240265

摘要/Abstract

摘要：

肌醇是一种“生物活素”，参与体内代谢和免疫调节等活动，在预防和治疗某些疾病中显示潜在的应用价值。其中肌肉肌醇（Myo-inositol，MI）是最普遍存在的形式，高等动物若缺乏肌醇，将会出现生长停滞和毛发脱落等现象。D-手性肌醇（D-chiro-inositol，DCI）是肌醇9种异构体中具有旋光性的一种。近年来研究者们发现DCI除了具有肌醇促进肝脏脂代谢的功能外，还具有胰岛素增敏作用、降血糖、改善多囊卵巢综合征（polycystic ovary syndrome，PCOS）患者的排卵情况等功能。研究表明，MI联合DCI不仅可以改善卵巢功能和生育能力，而且还能调节激素平衡，改善月经失调，还具有抗氧化、抗衰老、抗炎等特殊的生理功能。MI和DCI联合应用在PCOS治疗的优势、MI和DCI联合用药的剂量等尚需更多动物基础实验和临床研究，还需注意长期应用的安全性以及个体差异性应答等。

关键词: 多囊卵巢综合征, 肌醇, 肌肉肌醇, D-手性肌醇, 胰岛素抵抗, 治疗

Abstract:

Inositol as a kind of "bioactines" participates in metabolism and other activities in the body such as immunity, suggesting the potential application in the prevention and treatment of some diseases. Myo-inositol (MI) is the most common form of inositol. If higher animals are deprived inositol, they could show growth arrest and hair loss and other phenomena. D-chiro-inositol (DCI) is one of the nine isomers of inositol with optical activity. The recent studies have showed that DCI not only has the function of promoting liver lipid metabolism, but also has the function of insulin sensitization, lowering blood glucose and improving ovulation in patients with polycystic ovary syndrome (PCOS). MI combined with DCI can not only improve ovarian function and fertility, but also regulate hormone balance, improve menstrual disorders, and have special physiological functions such as anti-oxidation, anti-aging and anti-inflammation. However, the advantages of the combined application of MI and DCI in the treatment of PCOS, and the doses of combined MI and DCI, etc., need to be furtherly studied in animal experiments and clinical practice, also including the safety of long-term treatment and individual differential response.

Key words: Polycystic ovary syndrome, Inositol, Myo-inositol, D-chiro-inositol, Insulin resistance, Therapy

田德吉尔, 冯晓玲. 肌肉肌醇与D-手性肌醇在多囊卵巢综合征中的研究及应用[J]. 国际生殖健康/计划生育杂志, 2024, 43(6): 512-517.

TIAN Dejier, FENG Xiao-ling. Possible Application of Myo-Inositol and D-Chiro-Inositol in Treatment of Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(6): 512-517.

参考文献 34

[1]	Lete I, Martínez A, Lasaga I, et al. Update on the combination of myo-inositol/d-chiro-inositol for the treatment of polycystic ovary syndrome[J]. Gynecol Endocrinol, 2024, 40(1):2301554. doi: 10.1080/09513590.2023.2301554.
[2]	Ting Z, Xinghua T, Xiao X, et al. The impact of androgen levels on serum metabolic profiles in patients with polycystic ovary syndrome[J]. Gynecol Endocrinol, 2024, 40(1):2352136. doi: 10.1080/09513590.2024.2352136.
[3]	Dapas M, Dunaif A. Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification[J]. Endocr Rev, 2022, 43(6):927-965. doi: 10.1210/endrev/bnac001. pmid: 35026001
[4]	Chen X, Hong L, Diao L, et al. Hyperandrogenic environment regulates the function of ovarian granulosa cells by modulating macrophage polarization in PCOS[J]. Am J Reprod Immunol, 2024, 91(5):e13854. doi: 10.1111/aji.13854.
[5]	Khatun A, Nasrin T, Hassan MS, et al. A review on the nexus of autophagy genes from the perspective of polycystic ovary syndrome[J]. Biol Cell, 2024, 116(7):e2300069. doi: 10.1111/boc.202300069.
[6]	Zhao W, Li Z, Cai B, et al. Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients[J]. Reprod Biol Endocrinol, 2024, 22(1):43. doi: 10.1186/s12958-024-01212-y.
[7]	Li X, Yang J, Blockeel C, et al. Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome[J]. Acta Obstet Gynecol Scand, 2024, 103(8):1606-1614. doi: 10.1111/aogs.14863.
[8]	Xin C, Zhao M, Wang J, et al. Hawthorn polyphenols, D-chiro-inositol, and epigallocatechin gallate exert a synergistic hypoglycemic effect[J]. J Food Biochem, 2021, 45(7):e13771. doi: 10.1111/jfbc.13771.
[9]	Pustotina O, Myers SH, Unfer V, et al. The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40∶1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria[J]. Gynecol Obstet Invest, 2024, 89(2):131-139. doi: 10.1159/000536163. pmid: 38295772
[10]	Dinicola S, Unfer V, Facchinetti F, et al. Inositols: From Established Knowledge to Novel Approaches[J]. Int J Mol Sci, 2021, 22(19):10575. doi: 10.3390/ijms221910575.
[11]	Sairally B, Dhillon-Smith RK, Jethwani G, et al. Myoinositol or D-chiro-inositol for PCOS symptoms in adolescents: a narrative review[J]. J Pediatr Endocrinol Metab, 2024, 37(2):91-101. doi: 10.1515/jpem-2023-0458. pmid: 38117862
[12]	Bevilacqua A, Bizzarri M. Inositols in Insulin Signaling and Glucose Metabolism[J]. Int J Endocrinol, 2018,2018:1968450. doi: 10.1155/2018/1968450.
[13]	Fitz V, Graca S, Mahalingaiah S, et al. Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines[J]. J Clin Endocrinol Metab, 2024, 109(6):1630-1655. doi: 10.1210/clinem/dgad762.
[14]	Zhang Y, Li C, Zhang W, et al. Decreased Insulin Resistance by Myo-Inositol Is Associated with Suppressed Interleukin 6/Phospho-STAT3 Signaling in a Rat Polycystic Ovary Syndrome Model[J]. J Med Food, 2020, 23(4):375-387. doi: 10.1089/jmf.2019.4580. pmid: 32045334
[15]	Wu H, Yang M, Yan C, et al. Tenascin C activates the toll-like receptor 4/NF-κB signaling pathway to promote the development of polycystic ovary syndrome[J]. Mol Med Rep, 2024, 29(6):106. doi: 10.3892/mmr.2024.13230.
[16]	Yu S, Hou C, Zhang X, et al. Mesencephalic astrocyte-derived neurotrophic factor ameliorates inflammatory response in polycystic ovary syndrome via inhibiting TLR4-NF-κB-NLRP3 pathway[J]. Biochem Biophys Res Commun, 2024,707:149782. doi: 10.1016/j.bbrc.2024.149782.
[17]	Fedeli V, Catizone A, Querqui A, et al. The Role of Inositols in the Hyperandrogenic Phenotypes of PCOS: A Re-Reading of Larner′s Results[J]. Int J Mol Sci, 2023, 24(7):6296. doi: 10.3390/ijms24076296.
[18]	Carlomagno G, Unfer V, Roseff S. The D-chiro-inositol paradox in the ovary[J]. Fertil Steril, 2011, 95(8):2515-2516. doi: 10.1016/j.fertnstert.2011.05.027. pmid: 21641593
[19]	Laganà AS, Myers SH, Forte G, et al. Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future[J]. Expert Opin Drug Metab Toxicol, 2024, 20(1/2):61-72. doi: 10.1080/17425255.2024.2306851.
[20]	Greff D, Juhász AE, Váncsa S, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials[J]. Reprod Biol Endocrinol, 2023, 21(1):10. doi: 10.1186/s12958-023-01055-z.
[21]	Benelli E, Del Ghianda S, Di Cosmo C, et al. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women[J]. Int J Endocrinol, 2016,2016:3204083. doi: 10.1155/2016/3204083.
[22]	De Diego MV, Gómez-Pardo O, Groar JK, et al. Metabolic impact of current therapeutic strategies in Polycystic Ovary Syndrome: a preliminary study[J]. Arch Gynecol Obstet, 2020, 302(5):1169-1179. doi: 10.1007/s00404-020-05696-y. pmid: 32770354
[23]	Bahadur A, Arora H, Ravi A K, et al. Comparison of clinical, metabolic and hormonal effects of metformin versus combined therapy of metformin with myoinositol plus D-chiro-inositol in women with polycystic ovary syndrome(PCOS): a randomized controlled trial[J]. Cureus, 2021, 13(6):e15510. doi:10.7759/cureus.15510.
[24]	Bevilacqua A, Dragotto J, Giuliani A, et al. Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model[J]. J Cell Physiol, 2019, 234(6):9387-9398. doi: 10.1002/jcp.27623. pmid: 30317628
[25]	Januszewski M, Issat T, Jakimiuk AA, et al. Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome(PCOS)[J]. Ginekol Pol, 2019, 90(1):7-10. doi: 10.5603/GP.2019.0002. pmid: 30756365
[26]	Basciani S, Nordio M, Dinicola S, et al. Diet plus inositols, α-lactalbumin and Gymnema sylvestre: the successful combo to restore body weight and metabolic profile in obese and dysmetabolic patients[J]. Nutrients, 2023, 15(14):3142. doi: 10.3390/nu15143142.
[27]	Nordio M, Basciani S, Camajani E. The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios[J]. Eur Rev Med Pharmacol Sci, 2019, 23(12):5512-5521. doi: 10.26355/eurrev_201906_18223.
[28]	Mendoza N, Diaz-Ropero MP, Aragon M, et al. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial[J]. Gynecol Endocrinol, 2019, 35(8):695-700. doi: 10.1080/09513590.2019.1576620. pmid: 30880505
[29]	Facchinetti F, Orrù B, Grandi G, et al. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials[J]. Gynecol Endocrinol, 2019, 35(3):198-206. doi: 10.1080/09513590.2018.1540578. pmid: 30614282
[30]	Shokrpour M, Foroozanfard F, Afshar Ebrahimi F, et al. Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial[J]. Gynecol Endocrinol, 2019, 35(5):406-411. doi: 10.1080/09513590.2018.1540570. pmid: 30608001
[31]	Li YY, Peng YQ, Yang YX, et al. Baicalein improves the symptoms of polycystic ovary syndrome by mitigating oxidative stress and ferroptosis in the ovary and gravid placenta[J]. Phytomedicine, 2024,128:155423. doi: 10.1016/j.phymed.2024.155423.
[32]	Zhang R, Hu K, Bai H, et al. Increased oxidative stress is associated with hyperandrogenemia in polycystic ovary syndrome evidenced by oxidized lipoproteins stimulating rat ovarian androgen synthesis in vitro[J]. Endocrine, 2024, 84(3):1238-1249. doi: 10.1007/s12020-024-03726-2.
[33]	Nawrocka-Rutkowska J, Szydłowska I, Jakubowska K, et al. The Role of Oxidative Stress in the Risk of Cardiovascular Disease and Identification of Risk Factors Using AIP and Castelli Atherogenicity Indicators in Patients with PCOS[J]. Biomedicines, 2022, 10(7):1700. doi: 10.3390/biomedicines10071700.
[34]	Qi L, Li Y, Zhang L, et al. Immune and oxidative stress disorder in ovulation-dysfunction women revealed by single-cell transcriptome[J]. Front Immunol, 2023,14:1297484. doi: 10.3389/fimmu.2023.1297484.