| 马合红,侯秀真,冯妙肖,等.萝卜硫素调节腺苷酸活化蛋白激酶 /沉默信息调节器 1/过氧化物酶体增殖活化受体 γ辅助活化因子 1α信号通路对妊娠高血压大鼠妊娠结局的影响[J].安徽医药,2024,28(4):666-672. |
| 萝卜硫素调节腺苷酸活化蛋白激酶 /沉默信息调节器 1/过氧化物酶体增殖活化受体 γ辅助活化因子 1α信号通路对妊娠高血压大鼠妊娠结局的影响 |
| Impact of sulforaphane on the pregnancy outcome of gestational hypertensive rats by regulating adenylate-activated protein kinase/silent information regulator 1/ peroxisome proliferator-activated receptor gamma coactivator 1α signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2024.04.006 |
| 中文关键词: 高血压，妊娠性 萝卜硫素 AMPK/SIRT1/PGC-1ɑ信号通路 大鼠， Sprague-Dawley 妊娠结局 |
| 英文关键词: Hypertension, pregnancy-induced Sulforaphane AMPK/SIRT1/PGC-1ɑ signaling pathway Rats, Sprague-Dawley Pregnancy outcome |
| 基金项目:沧州市科技计划项目( 131302110) |
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| 中文摘要: |
| 目的探究萝卜硫素( SFN)通过调节腺苷酸活化蛋白激酶( AMPK)/沉默信息调节器 1(SIRT1)/过氧化物酶体增殖活化受体 γ辅助活化因子 1α(PGC-1α)信号通路对妊娠期高血压疾病( HDP)大鼠妊娠结局的影响。方法 2021年 3月至 2022年 6月， 70只雌性大鼠受孕后分为对照组、 HDP组、 SFN-L组( SFN 5 mg/kg)、 SFN-M(SFN 15 mg/kg)、 SFN-H(SFN 30 mg/kg)、硫酸镁组(硫酸镁注射液 100 mg/kg)、 Compound C组( SFN 30 mg/kg+AMPK抑制剂 Compound C 0.25 mg/kg)，各组 10只。在妊娠第 13天起除对照组，其余各组妊娠大鼠尾静脉注射 7 mg/kg L-NAME，连续注射 4d，建立 HDP大鼠模型，对照组大鼠尾静脉注射0.9%氯化钠溶液。从造模成功后第 1天(妊娠第 17天)起，各给药组注射相应剂量的药物，对照组、 HDP组注射 0.9%氯化钠溶液，连续给药至妊娠第 20天。检测妊娠第 17天和第 20天各组大鼠尾动脉压和 24 h尿蛋白定量水平；试剂盒法检测大鼠血肌(SCr)和血尿素氮(BUN)水平；观察检测大鼠妊娠结局指标； HE染色观察胎盘组织和肾脏组织病理情况；蛋白质印迹法检测胎酐盘组织可溶性血管内皮生长因子受体 -1(sFLT-1)、胎盘生长因子( PLGF)、内皮型一氧化氮合酶( eNOs)、磷酸化 eNOs(peNOs)、磷酸化 AMPK(p-AMPK)、 AMPK、SIRT1、PGC-1ɑ蛋白水平。结果 HDP组大鼠血压［( 152.52±4.79)mmHg比( 101.63±4.15)mmHg］、 24 h尿蛋白定量水平［( 679.38±64.32)mg/L比( 123.17±20.19)mg/L］、胎鼠病死率［( 28.57±2.08)%比( 0.96±0.11)%］、血清 SCr和 BUN水平、胎盘组织 sFLT-1表达水平高于对照组( P<0.05)，而胎鼠质量［( 2.32±0.19)g比( 4.75±0.43)g］、产仔数［( 11.70±0.69)个比( 7.10±0.57)个］、胎盘质量［( 0.32±0.06)g比( 0.58±0.12)g］、胎盘组织 PLGF、p-eNOs、p-AMPK、SIRT1和 PGC-1ɑ蛋白表达低于对照组( P<0.05)另外， HDP大鼠胎盘组织绒毛数量减少，胎盘结构缩小，部分绒毛显示纤维蛋白样坏死，肾脏组织内肾小球数目减少，结常； SFN-L组、 SFN-M组、 SFN-H组和硫酸镁组大鼠血压［( 136.91±5.16)mmHg、构异，(129.25±4.54)mmHg、(117.33±4.19)mmHg、(121.72±4.61)mmHg比( 152.52±4.79)mmHg］、 24 h尿蛋白定量水平［( 595.91±53.05)mg/L、(532.23±49.76)mg/L、(461.16±35.15)mg/L、(482.74±39.58)mg/L比( 679.38±64.32)mg/L］、胎鼠病死率、血清 SCr和 BUN水平、胎盘组织 sFLT-1表达水平低于 HDP组( P<0.05)，胎鼠质量、产仔数、胎盘质量、胎盘组织 PLGF、p-eNOs、p-AMPK、 SIRT1和 PGC-1ɑ蛋白表达高于 HDP组( P<0.05)，胎盘组织和肾脏组织结构异常程度减轻； AMPK抑制剂 Compound C减弱了 SFN对 HDP大鼠血压、肾损伤和妊娠结局的保护作用。结论 SFN通过激活 AMPK/SIRT1/PGC-1ɑ信号通路改善 HDP大鼠妊娠结局。 |
| 英文摘要: |
| Objective To explore the impact of sulforaphane (SFN) on pregnancy outcome in hypertensive disorder of pregnancy(HDP) rats through regulation of adenylate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1)/peroxisome prolifera? tor-activated receptor gamma coactivator 1α (PGC-1α) signaling pathway.Methods From March 2021 to June 2022, after conception, 70 female rats were grouped into control group, HDP group, SFN-L group (SFN 5 mg/kg), SFN-M (SFN 15 mg/kg), SFN-H (SFN 30 mg/kg), magnesium sulfate group (magnesium sulfate 100 mg/kg), Compound C group (SFN 30 mg/kg + AMPK inhibitor Compound C 0.25mg/kg), 10 rats in each group. From the 13th day of pregnancy, except the control group, the other pregnant rats were injected with 7mg/kg L-NAME through the tail vein for 4 consecutive days to establish the HDP rat model, while the rats in the control group were in?jected with normal saline through the tail vein. From the first day after successful modeling (the 17th day of pregnancy), each adminis?tration group was injected with the corresponding dose of drugs, and the control group and HDP group were injected with normal saline,and the administration continued until the 20th day of pregnancy. The tail arterial pressure and 24 h urine protein quantitative level ofrats in each group were detected on the 17th and 20th day of pregnancy. Kit method was used to detect the levels of serum creatinine(SCr) and blood urea nitrogen (BUN) in rats; the pregnancy outcome indicators of rats were observed and detected; HE staining wasused to observe the pathological conditions of placental tissue and kidney tissue; Western blotting was used to detect the protein levelsof soluble vascular endothelial growth factor recepter-1 (sFLT-1), placental growth factor (PLGF), endothelial nitric oxide synthase (eNOs), phosphorylated eNOs (p-eNOs), phosphorylated AMPK (p-AMPK), AMPK, SIRT1 and PGC-1α in placenta tissue. Results The blood pressure [(152.52±4.79) mmHg vs. (101.63±4.15) mmHg], 24 h urine protein quantitative level [(679.38±64.32) mg/L vs. (123.17±20.19) mg/L)], fetal mortality [(28.57±2.08) % vs. (0.96±0.11) %], serum SCr and BUN levels, and placental tissue sFLT-1 ex? pression level were higher in the HDP group than those in the control group (P<0.05), while fetal weight [(2.32±0.19) g vs. (4.75±0.43) g], litter size (11.70±0.69 vs. 7.10±0.57), placental quality [(0.32±0.06) g vs. (0.58±0.12) g], and the PLGF, p-AMPK, SIRT1 and PGC1α protein expressions in placental tissue were lower than those in the control group (P<0.05). Additionally, the number of villi in theplacental tissue of HDP rats was reduced, the structure of the placenta was reduced, some villi showed fibrin-like necrosis, and thenumber of glomeruli in the kidney tissue was reduced and the structure was abnormal. The blood pressure [(136.91±5.16) mmHg, (129.25±4.54) mmHg, (117.33±4.19) mmHg, (121.72±4.61) mmHg vs. (152.52±4.79) mmHg], 24 h urine protein quantitative level [(595.91±53.05) mg/L, (532.23±49.76) mg/L, (461.16±35.15) mg/L, (482.74±39.58) mg/L vs. (679.38±64.32) mg/L], fetal mortality, se? rum SCr and BUN levels, and placental tissue sFLT-1 expression were lower in the SFN-L, SFN-M, SFN-H groups and magnesium sul? fate group than those in the HDP group (P<0.05), while fetal weight , litter size, placental quality, placental tissue PLGF, p-eNOs, p-AMPK, SIRT1 and PGC-1ɑ protein expressions were higher than those in the HDP group (P<0.05). The abnormal degree of placentaltissue and kidney tissue structure was reduced; the AMPK inhibitor Compound C attenuated the protective effects of SFN on blood pres?sure, kidney injury, and pregnancy outcomes in HDP rats.Conclusion SFN improves pregnancy outcomes in HDP rats by activating AMPK/SIRT1/PGC-1α signaling pathway. |
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