Sheibani Lili, Lechuga Thomas J, Zhang Honghai, Hameed Afshan, Wing Deborah A, Kumar Sathish, Rosenfeld Charles R, Chen Dong-Bao
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Department of Obstetrics and Gynecology, University of Texas Medical Branch-Galveston, Galveston, Texas, USA.
Biol Reprod. 2017 Mar 1;96(3):664-672. doi: 10.1095/biolreprod.116.143834.
Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.
通过胱硫醚-β-合酶（CBS）和胱硫醚-γ-裂解酶（CSE）代谢L-半胱氨酸合成的内源性硫化氢（H2S）是一种强效血管舒张剂和血管生成因子。本研究的目的是确定在月经周期和怀孕期间，人子宫动脉（UA）中H2S的产生是否会随着CBS和/或CSE表达和/或活性的增加而增加，以及外源性H2S是否会使UA舒张。研究了来自非妊娠（NP）绝经前月经周期增殖期（pPRM）和分泌期（sPRM）以及妊娠（P）妇女的子宫动脉。通过亚甲蓝法测量H2S的产生。通过定量实时PCR评估CBS和CSE mRNA，通过免疫印迹和半定量免疫荧光显微镜评估蛋白质。通过离体钢丝肌动描记法确定H2S对大鼠UA舒张的影响。NP pPRM和P组的UA中H2S产生量高于NP sPRM组，且被特异性CBS抑制剂而非CSE抑制剂抑制。NP pPRM和P组的UA中CBS mRNA和蛋白高于NP sPRM组，而CSE则无差异。CBS蛋白定位于内皮和平滑肌，其水平按P>NP pPRM组UA>sPRM组UA的定量顺序排列。CSE蛋白定位于UA内皮和平滑肌，各组间无差异。H2S供体使P组UA舒张，但对肠系膜动脉无作用。因此，人UA中H2S的产生随着内皮和平滑肌中CBS上调而增加，有助于在月经周期增殖期和妊娠等雌激素主导的生理状态下UA血管舒张。
