| 吴益青,计 静,李亚妮,邢燕妮,王 瑞.L-瓜氨酸对子痫前期中的氧化应激和滋养层细胞侵袭的调控机制研究[J].,2023,(2):232-238 |
| L-瓜氨酸对子痫前期中的氧化应激和滋养层细胞侵袭的调控机制研究 |
| The Regulatory Mechanism of L-Citrulline on Oxidative Stress and Trophoblast Invasion in Preeclampsia |
| 投稿时间：2022-06-30 修订日期：2022-07-27 |
| DOI：10.13241/j.cnki.pmb.2023.02.006 |
| 中文关键词: 子痫前期 L-瓜氨酸 氧化应激 滋养层细胞 侵袭 |
| 英文关键词: Preeclampsia L-citrulline Oxidative stress Trophoblast Invasion |
| 基金项目:陕西省重点研发计划项目-社会发展领域（2021SF-009） |
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| 中文摘要: |
| 摘要 目的：研究L-瓜氨酸（L-Cit）对子痫前期（PE）大鼠模型的治疗作用，及其对氧化应激和滋养层细胞侵袭的影响。方法：建立N-硝基-L-精氨酸甲酯（L-NAME）诱导的PE大鼠模型后，将大鼠分为Control组、PE组、PE+低、中和高剂量L-Cit组（依次为L-L-Cit、M-L-Cit和H-L-Cit组，剂量依次为100、200和500 mg/kg），n=6，连续给药7 d。在孕第21 d时，检测各组大鼠收缩压（SBP）、24 h尿蛋白、血清超氧化物歧化酶（SOD）和丙二醛（MDA）水平，并对胎盘组织进行苏木精伊红（HE）染色。将HTR-8/Svneo细胞分为Control组、缺氧/复氧（H/R）组、H/R+L-Cit组和H/R+L-Cit+sc-221593组，分别对细胞进行H/R处理，并使用L-Cit（200 μg/mL）和特异性ERK1/2抑制剂sc-221593（10 μmol/L）培养细胞48 h。通过Transwell测定细胞侵袭。通过Western blotting检测total-ERK1/2、p-ERK1/2、total-p38、p-p38、基质金属蛋白酶（MMP）-2和MMP-9的蛋白表达。结果：与PE组比较，L-L-Cit组、M-L-Cit组和H-L-Cit组的SBP和24 h尿蛋白水平均降低（P<0.05）；胎盘组织形态明显改善；血清SOD升高，MDA降低（P<0.05）；胎盘组织中ERK1/2和p38的磷酸化水平及MMP-2和MMP-9的蛋白表达水平均升高（P<0.05）。与H/R组比较，H/R+L-Cit组的侵袭细胞数量升高（P<0.05）；ERK1/2和p38的磷酸化水平及MMP-2和MMP-9的蛋白表达水平均升高（P<0.05）。与H/R+L-Cit组比较，H/R+L-Cit+sc-221593组的上述变化均被逆转（P<0.05）。结论：L-Cit可能通过激活ERK/JNK通路减轻PE中的氧化应激并促进滋养层细胞侵袭，从而减轻PE症状。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the therapeutic effect of L-Citrulline (L-Cit) on preeclampsia (PE) rat model and its effect on oxidative stress and trophoblast cell invasion. Methods: After establishing the PE rat model induced by N-nitro-L-arginine methyl ester (L-NAME), the rats were divided into Control group, PE group, PE+ low, middle and high dose L-Cit groups (L-L-Cit, M-L-Cit and H-L-Cit groups in sequence, with doses of 100, 200 and 500 mg/kg in sequence), n=6, continuous administration for 7 days. On the 21st day of pregnancy, systolic blood pressure (SBP), 24-hour urinary protein, serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured, and placental tissue was stained with hematoxylin-eosin (HE). The HTR-8/Svneo cells were divided into Control group, hypoxia/reoxygenation (H/R) group, H/R+L-Cit group and H/R+L-Cit+sc-221593 group. The cells were treated with H/R, respectively, and cultured with L-Cit (200 μg/mL) and the specific ERK1/2 inhibitor sc-221593 (10 μmol/L) for 48 h. Cell invasion was determined by Transwell assay. The protein expressions of total-ERK1/2, p-ERK1/2, total-p38, p-p38, matrix metalloproteinase (MMP)-2 and MMP-9 in placental tissues and cells were detected by Western blotting. Results: Compared with PE group, the SBP and 24 h urinary protein levels of the rats in L-L-Cit group, M-L-Cit group and H-L-Cit group were decreased(P<0.05); the placental tissue morphology was significantly improved; serum SOD was increased, while MDA was decreased(P<0.05); the phosphorylation levels of ERK1/2 and p38 and the protein expression levels of MMP-2 and MMP-9 in placental tissue were increased (P<0.05). Compared with H/R group, the number of invasive cells in H/R+L-Cit group increased(P<0.05); the phosphorylation levels of ERK1/2 and p38 and the protein expression levels of MMP-2 and MMP-9 increased(P<0.05). Compared with the H/R+L-Cit group, the above changes in the H/R+L-Cit+sc-221593 group were reversed(P<0.05). Conclusion: L-Cit may alleviate the symptoms of PE by reducing oxidative stress in PE and promoting trophoblast invasion by activating the ERK/JNK pathway. |
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