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多囊卵巢综合征中的高同型半胱氨酸血症:降低甜菜碱-同型半胱氨酸甲基转移酶和胱硫醚 β-合酶介导的同型半胱氨酸代谢。

Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism.

机构信息

Centre of Reproductive Medicine, ShengJing Hospital of China Medical University, Shenyang 110004, China.

Department of Obstetrics and Gynecology, ShengJing Hospital of China Medical University, Shenyang 110004, China.

出版信息

Reprod Biomed Online. 2018 Aug;37(2):234-241. doi: 10.1016/j.rbmo.2018.05.008. Epub 2018 May 22.

Abstract

RESEARCH QUESTION

What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)?

DESIGN

Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD).

RESULTS

It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia.

CONCLUSIONS

These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS.

摘要

研究问题

多囊卵巢综合征(PCOS)患者血液中同型半胱氨酸的代谢特点是什么?

设计

在非肥胖和肥胖对照组以及 PCOS 患者的血清样本中测定同型半胱氨酸浓度。使用脱氢表雄酮(DHEA)或 DHEA 联合高脂肪饮食(HFD)建立 PCOS 大鼠模型,研究同型半胱氨酸代谢。

结果

结果表明,(i)肥胖组 PCOS 患者血清同型半胱氨酸浓度高于对照组(P<0.05),且肥胖组无论是否存在 PCOS 状态,血清同型半胱氨酸浓度均显著高于非肥胖组(均 P<0.05);(ii)与对照组相比,DHEA+HFD 诱导的大鼠血清同型半胱氨酸浓度显著升高(P<0.05);(iii)与对照组相比,DHEA+HFD 诱导的大鼠肝组织中同型半胱氨酸代谢酶 Bhmt 和 Cbs 的 mRNA 浓度显著降低(均 P<0.0001);(iv)与对照组相比,DHEA+HFD 组 Cbs(P<0.05)和 Bhmt(P<0.05 和 P<0.0001)启动子的甲基化浓度显著降低。这些甲基化模式,加上之前的数据,表明 Bhmt 和 Cbs 启动子的低甲基化介导的转录激活可能是一种防御机制,可对抗与 PCOS 相关的高同型半胱氨酸血症。

结论

这些发现表明,肝脏 Bhmt 和 Cbs 介导的同型半胱氨酸代谢减少可能在 PCOS 中的高同型半胱氨酸血症中起作用,并为肝脏功能下降在 PCOS 中的潜在作用提供了进一步的证据。

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