مروری بر برخی جنبه‌های متابولیکی بیماری پره‌اکلامپسی

خسروبیگی, علی

مروری بر برخی جنبه‌های متابولیکی بیماری پره‌اکلامپسی

نوع مقاله : مقاله مروری

نویسنده

علی خسروبیگی

دانشیار، گروه بیوشیمی، دانشکده‌‌ی پزشکی، دانشگاه علوم پزشکی لرستان، خرم‌آباد، ایران

چکیده

مقدمه: پره‌اکلامپسی یک سندرم خاص بارداری است که عامل بسیار مهم مرگ و میر مادر و نوزاد و نیز تولد نوزادان نارس در جهان محسوب می‌گردد. این بیماری با افزایش فشار خون و پروتئین‌اوری پس از هفته‌ی 20 بارداری شناخته می‌شود. اگر چه فرضیه‌های متعددی در رابطه با بیماری پره‌اکلامپسی پیشنهاد شده است، اما علت واقعی آن در حال حاضر مشخص نیست. در این مقاله‌ی مروری آدیپوکین‌های لپتین و آدیپونکتین و نیز متابولیت هموسیستئن و اهمیت آنتی‌اکسیدان‌ها در بیماری پره‌اکلامپسی مورد بحث قرار گرفتند.روش‌ها: جهت جستجوی مقالات از پایگاه‌های اطلاعاتی PubMed و Scopus استفاده گردید.یافته‌ها: اکثر مطالعات افزایش غلظت سرمی لپتین را در پره‌اکلامپسی گزارش داده‌اند و برای آن هم نقش پاتولوژیکی و هم یک پاسخ جبرانی مطرح است. مقادیر بالا و پایین آدیپونکتین همراه با تفسیر‌هایی برای هر کدام از آن‌ها در پره‌اکلامپسی گزارش شده است. مطالعات سال‌های اخیر نشان داده است که هیپرهموسیستئینمی ممکن است سبب افزایش خطر ابتلا به پره‌اکلامپسی گردد. اکثر مطالعات کارآزمایی بالینی نشان‌دهنده‌ی غیر مؤثر بودن مکمل‌های آنتی‌اکسیدان در جلوگیری از خطر بروز پره‌اکلامپسی است.نتیجه‌گیری: نقش آنتی‌اکسیدانتی احتمال آدیپونکتین در پره‌اکلامپسی نیازمند مطالعات بیشتر است. مطالعاتی برای روشن شدن مکانیسم اثر هیپرهموسیستئینمی در پاتوژنز پره‌اکلامپسی می‌تواند پیشنهاد گردد. مطالعات کارآزمایی بالینی بیشتری جهت مشخص نمودن اهمیت استفاده از مکمل‌های آنتی‌اکسیدان در جلوگیری بروز پره‌اکلامپسی و یا درمان آن لازم می‌باشد.

کلیدواژه‌ها

عنوان مقاله [English]

Review on Some Metabolic Aspects of Preeclampsia

نویسنده [English]

Ali Khosrowbeygi

Associate Professor, Department of Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

چکیده [English]

Background: Preeclampsia, a pregnancy specific syndrome, is a major cause of maternal and infant morbidity/mortality and preterm delivery worldwide. It is characterized by the onset of hypertension and proteinuria after 20 weeks of gestation. Despite a fairly high incidence, the underlying etiology of preeclampsia is still incomplete. In the present study, adipokines leptin and adiponectin, the metabolite homocysteine and the importance of antioxidants in preeclampsia was reviewed.Methods: The PubMed and Scopus databases were used for searching the relevant studies.Findings: The majority of studies reported hyperleptinemia in preeclampsia and suggested a pathological role and also a compensatory response for it. There were some conflicting findings of maternal circulating levels of adiponectin in women with preeclampsia with relevant explanations. Recent studies indicated that hyperhomocysteinemia might be associated with an increased risk of preeclampsia. The majority of trials to date have found routine antioxidant supplementation during pregnancy to be ineffective in reducing the risk of preeclampsia.Conclusion: More studies are needed to explore possible antioxidant property of adiponectin in preeclampsia. It might be proposed exploring the mechanism of hyperhomocysteinemia on the pathogenesis of preeclampsia. Further clinical trials are needed to address the importance of using antioxidants during pregnancy for the prevention or treatment of preeclampsia.

کلیدواژه‌ها [English]

Preeclampsia
Leptin
Adiponectin
Homocysteine
Antioxidant

مراجع

Eiland E, Nzerue C, Faulkner M. Preeclampsia 2012. J Pregnancy 2012; 2012: 586578.
Mohaupt M. Molecular aspects of preeclampsia. Mol Aspects Med 2007; 28(2): 169-91.
Mutter WP, Karumanchi SA. Molecular mechanisms of preeclampsia. Microvasc Res 2008; 75(1): 1-8.
Amirian T, Rahgozar S, Shahshahan Z. Preeclampsia in a Cellular and Molecular View. J Isfahan Med Sch 2013; 31(234): 565-80. [In Persian].
Kestlerova A, Feyereisl J, Frisova V, Mechurova A, Sula K, Zima T, et al. Immunological and biochemical markers in preeclampsia. J Reprod Immunol 2012; 96(1-2): 90-4.
Staff AC, Dechend R, Redman CW. Review: Preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: Two new hypotheses. Placenta 2013; 34(Suppl): S73-S78.
Sharma A, Satyam A, Sharma JB. Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women. Am J Reprod Immunol 2007; 58(1): 21-30.
Ouyang Y, Chen H, Chen H. Reduced plasma adiponectin and elevated leptin in pre-eclampsia. Int J Gynaecol Obstet 2007; 98(2): 110-4.
Nakatsukasa H, Masuyama H, Takamoto N, Hiramatsu Y. Circulating leptin and angiogenic factors in preeclampsia patients. Endocr J 2008; 55(3): 565-73.
Aydin S, Guzel SP, Kumru S, Aydin S, Akin O, Kavak E, et al. Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women. J Physiol Biochem 2008; 64(1): 51-9.
Lu D, Yang X, Wu Y, Wang H, Huang H, Dong M. Serum adiponectin, leptin and soluble leptin receptor in pre-eclampsia. Int J Gynaecol Obstet 2006; 95(2): 121-6.
Ouyang YQ, Li SJ, Zhang Q, Xiang WP, Shen HL, Chen HP, et al. Plasma sFlt-1-to-PlGF ratio is correlated with inflammatory but not with oxidative stress in Chinese preeclamptic women. Arch Gynecol Obstet 2009; 280(1): 91-7.
Herse F, Bai Y, Staff AC, Yong-Meid J, Dechend R, Zhou R. Circulating and uteroplacental adipocytokine concentrations in preeclampsia. Reprod Sci 2009; 16(6): 584-90.
Briana DD, Malamitsi-Puchner A. Reviews: adipocytokines in normal and complicated pregnancies. Reprod Sci 2009; 16(10): 921-37.
Tal R. The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis. Biol Reprod 2012; 87(6): 134.
Miehle K, Stepan H, Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 2012; 76(1): 2-11.
Khosrowbeygi A, Ahmadvand H. Maternal serum levels of adiponectin in preeclampsia. J Ayub Med Coll Abbottabad 2009; 21(3): 79-82.
Takemura Y, Osuga Y, Koga K, Tajima T, Hirota Y, Hirata T, et al. Selective increase in high molecular weight adiponectin concentration in serum of women with preeclampsia. J Reprod Immunol 2007; 73(1): 60-5.
Nien JK, Mazaki-Tovi S, Romero R, Erez O, Kusanovic JP, Gotsch F, et al. Adiponectin in severe preeclampsia. J Perinat Med 2007; 35(6): 503-12.
Mazaki-Tovi S, Romero R, Vaisbuch E, Kusanovic JP, Erez O, Gotsch F, et al. Maternal serum adiponectin multimers in preeclampsia. J Perinat Med 2009; 37(4): 349-63.
Odden N, Henriksen T, Holter E, Grete SA, Tjade T, Morkrid L. Serum adiponectin concentration prior to clinical onset of preeclampsia. Hypertens Pregnancy 2006; 25(2): 129-42.
Haugen F, Ranheim T, Harsem NK, Lips E, Staff AC, Drevon CA. Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression. Am J Physiol Endocrinol Metab 2006; 290(2): E326-E333.
Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, et al. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 2007; 115(11): 1408-16.
Prior SL, Tang TS, Gill GV, Bain SC, Stephens JW. Adiponectin, total antioxidant status, and urine albumin excretion in the low-risk "Golden Years" type 1 diabetes mellitus cohort. Metabolism 2011; 60(2): 173-9.
Khosrowbeygi A, Ahmadvand H. Positive correlation between serum levels of adiponectin and homocysteine in pre-eclampsia. J Obstet Gynaecol Res 2013; 39(3): 641-6.
Murphy MM, Fernandez-Ballart JD. Homocysteine in pregnancy. Adv Clin Chem 2011; 53: 105-37.
Mao D, Che J, Li K, Han S, Yue Q, Zhu L, et al. Association of homocysteine, asymmetric dimethylarginine, and nitric oxide with preeclampsia. Arch Gynecol Obstet 2010; 282(4): 371-5.
Makedos G, Papanicolaou A, Hitoglou A, Kalogiannidis I, Makedos A, Vrazioti V, et al. Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia. Arch Gynecol Obstet 2007; 275(2): 121-4.
Acilmis YG, Dikensoy E, Kutlar AI, Balat O, Cebesoy FB, Ozturk E, et al. Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia. J Obstet Gynaecol Res 2011; 37(1): 45-50.
Braekke K, Ueland PM, Harsem NK, Karlsen A, Blomhoff R, Staff AC. Homocysteine, cysteine, and related metabolites in maternal and fetal plasma in preeclampsia. Pediatr Res 2007; 62(3): 319-24.
Hasanzadeh M, Ayatollahi H, Farzadnia M, Ayati S, Khoob MK. Elevated plasma total homocysteine in preeclampsia. Saudi Med J 2008; 29(6): 875-8.
Hoque MM, Bulbul T, Mahal M, Islam NA, Ferdausi M. Serum homocysteine in pre-eclampsia and eclampsia. Bangladesh Med Res Counc Bull 2008; 34(1): 16-20.
Singh U, Gupta HP, Singh RK, Shukla M, Singh R, Mehrotra SS, et al. A study of changes in homocysteine levels during normal pregnancy and pre-eclampsia. J Indian Med Assoc 2008; 106(8): 503-5.
Atis A, Aydin Y, Basol E, Goker N. Troponin I and homocysteine levels in mild and severe preeclampsia. Clin Exp Obstet Gynecol 2010; 37(1): 21-3.
Wen SW, Chen XK, Rodger M, White RR, Yang Q, Smith GN, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 2008; 198(1): 45-7.
Rahimi Z, Malek-Khosravi S, Rahimi Z, Jalilvand F, Parsian A. MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress. Clin Biochem 2013; 46(1-2): 143-7.
Guo Y, Smith GN, Wen SW, Walker MC. Folate metabolism and preeclampsia. Fetal Matern Med Rev 2012; 23(2): 131-55.
Khosrowbeygi A, Lorzadeh N, Ahmadvand H, Shiravand Y. Homocysteine and its association with lipid Peroxidation and leptin in preeclampsia. Int J Biol Chem 2011; 5(3): 184-92.
Shenoy V, Kanasaki K, Kalluri R. Pre-eclampsia: connecting angiogenic and metabolic pathways. Trends Endocrinol Metab 2010; 21(9): 529-36.
Seol HJ, Cho GJ, Oh MJ, Kim HJ. 2-methoxyoestradiol levels and placental catechol-O-methyltransferase expression in patients with late-onset preeclampsia. Arch Gynecol Obstet 2013; 287(5): 881-6.
Khosrowbeygi A, Lorzadeh N, Ahmadvand H. Lipid peroxidation is not associated with adipocytokines in preeclamptic women. Iran J Reprod Med 2011; 9(2): 113-18.
Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012; 10: 49.
Mert I, Oruc AS, Yuksel S, Cakar ES, Buyukkagnici U, Karaer A, et al. Role of oxidative stress in preeclampsia and intrauterine growth restriction. J Obstet Gynaecol Res 2012; 38(4): 658-64.
Rani N, Dhingra R, Arya DS, Kalaivani M, Bhatla N, Kumar R. Role of oxidative stress markers and antioxidants in the placenta of preeclamptic patients. J Obstet Gynaecol Res 2010; 36(6): 1189-94.
Fenzl V, Flegar-Mestric Z, Perkov S, Andrisic L, Tatzber F, Zarkovic N, et al. Trace elements and oxidative stress in hypertensive disorders of pregnancy. Arch Gynecol Obstet 2013; 287(1): 19-24.
Kaur G, Mishra S, Sehgal A, Prasad R. Alterations in lipid peroxidation and antioxidant status in pregnancy with preeclampsia. Mol Cell Biochem 2008; 313(1-2): 37-44.
Salles AM, Galvao TF, Silva MT, Motta LC, Pereira MG. Antioxidants for preventing preeclampsia: a systematic review. ScientificWorldJournal 2012; 2012: 243476.
Wibowo N, Purwosunu Y, Sekizawa A, Farina A, Idriansyah L, Fitriana I. Antioxidant supplementation in pregnant women with low antioxidant status. J Obstet Gynaecol Res 2012; 38(9): 1152-61.
Khosrowbeygi A, Ahmadvand H. Serum total antioxidant capacity in patients with preeclampsia. Iran J Obstet Gynecol Infertil 2013; 16(47-48): 1-5. [In Persian].
Ozturk E, Balat O, Acilmis YG, Ozcan C, Pence S, Erel O. Measurement of the placental total antioxidant status in preeclamptic women using a novel automated method. J Obstet Gynaecol Res 2011; 37(4): 337-42.