| 刘艳,刘晓夏,朱一麟.基于血管紧张素 Ⅱ/一氧化氮信号通路探究 N-苄苯乙烯胺对妊娠期高血压模型大鼠的干预机制[J].安徽医药,2023,27(6):1093-1097. |
| 基于血管紧张素 Ⅱ/一氧化氮信号通路探究 N-苄苯乙烯胺对妊娠期高血压模型大鼠的干预机制 |
| Exploring the intervention mechanism of N-benzylphenethylamine in rats with gestational hypertension based on the angiotensin Ⅱ/nitric oxide signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2023.06.008 |
| 中文关键词: 高血压，妊娠性 肌酸酐 血管紧张素 Ⅱ 转录激活因子 3 过氧化脂质类 一氧化氮 肾功能 内皮功能 大鼠， Sprague-Dawley |
| 英文关键词: Hypertension, pregnancy-induced Creatinine Angiotensin Ⅱ Activating transcription factor 3 Lipid peroxide Nitric oxide Renal function Endothelial function Rats, Sprague-Dawley |
| 基金项目:国家自然科学基金资助项目( 82001584) |
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| 目的基于血管紧张素 Ⅱ/一氧化氮(AngⅡ/NO)信号通路探究 N-苄苯乙烯胺( AG490)对妊娠期高血压( HDCP)模型大鼠的干预机制。方法 2021年 1—5月，选取 30只雌性大鼠，随机数字表法选取 10只为正常组，其余 20只建立 HDCP模型，建模成功后使用随机数字表法分为 HDCP组、 AG490组各 10只， AG490组大鼠腹腔注射 5 mg/kg AG490，正常组、 HDCP组大鼠腹腔注射等量生理盐水。检测三组大鼠血压、平均动脉压、 24 h尿蛋白水平，免疫透射比浊法检测血肌酐、血尿素氮水平，酶联免疫吸附实验法检测炎症反应、氧化应激指标及 AngⅡ、NO水平。检测三组大鼠胎盘质量及胎鼠情况，蛋白质印迹法检测内源性酪氨酸蛋白激酶 2(JAK2)/信号传导和转录激活因子 3(STAT3)/细胞因子信号转导抑制因子 1(SOCS1)通路蛋白表达。结果 HDCP组大鼠收缩压、舒张压、平均动脉压水平分别为( 150.37±7.23)mmHg、(107.28±5.41)mmHg、(131.29±6.18)mmHg，AG490组大鼠收缩压、舒张压、平均动脉压水平分别为( 121.25±5.91)mmHg、(86.22±4.26)mmHg、(97.35±5.11)mmHg，与 HDCP组比较， AG490组大鼠血压、平均动脉压水平较低( P<0.05)。与 HDCP组比较， AG490组大鼠 24 h尿蛋白、血肌酐、血尿素氮水平较低( P<0.05)。与 HDCP组比较， AG490组大鼠 C反应蛋白( CRP)、白细胞介素 -1β(IL-1β)、过氧化脂水平较低，过氧化氢酶(CAT)水平较高(P<0.05)。与 HDCP组比较， AG490组大鼠胎盘质量、胎鼠体长、体质量较高( P<0.05)。 HDCP组大鼠 AngⅡ水平为( 67.81±7.69)ng/L，NO水平为( 41.17±5.39)moL/L，AG490组大鼠 AngⅡ水平为( 45.23±5.64)ng/L，NO水平为( 54.62±6.57) moL/L，与 HDCP组比较， AG490组大鼠 AngⅡ水平较低， NO水平较高( P<0.05)。与 HDCP组比较， AG490组大鼠 JAK2、STAT3、 SOCS1相对表达量较低( P<0.05)。结论使用 JAK2抑制剂 AG490对 HDCP模型大鼠进行干预，大鼠血压水平、肾功能明显改善，大鼠炎症反应、氧化应激减轻，胎鼠状况改善，大鼠内皮功能得到提升， JAK2/STAT3/SOCS1通路蛋白表达受到调控。 |
| 英文摘要: |
| Objective To explore the intervention mechanism of N-benzylphenylstyreneamine (AG490) on gestational hypertension(HDCP) rats based on the angiotensin Ⅱ/nitric oxide (Ang Ⅱ/NO) signaling pathway.Methods From January to May 2021, 30 femalerats were selected; 10 were selected as the normal group by the random number table method, and the remaining 20 were established asHDCP models. After successful modeling, they were divided into 10 rats each in the HDCP group and AG490 group using the randomnumber table method. Rats in the AG490 group were injected intraperitoneally with 5 mg/kg AG490, and rats in the normal group andHDCP group were injected intraperitoneally with equal amounts of saline. Blood pressure, mean arterial pressure and 24-h urinary protein, serum creatinine (Scr) and blood urea nitrogen (BUN) levels were determined by immunoturbidimetry, and inflammation response,oxidative stress index, Ang Ⅱ and NO levels were measured by enzyme-linked immunosorbent assay. The placental mass and fetal ratsin the three groups were measured. Western blotting was used to detect the expression of the endogenous tyrosine kinase 2 (JAK2)/signal transduction and transcription activator 3 (STAT3)/cytokine signal transduction inhibitor 1 (SOCS1) pathway.Results The systolic,diastolic and mean arterial pressure levels of the rats in the HDCP group were (150.37±7.23) mmHg, (107.28±5.41) mmHg and(131.29±6.18) mmHg, respectively, while the systolic, diastolic and mean arterial pressure levels of the rats in the AG490 group were(121.25±5.91) mmHg, (86.22±4.26) mmHg and (97.35±5.11) mmHg, respectively. Compared with the HDCP group, the blood pressureand mean arterial pressure levels were lower in the AG490 group of rats (P<0.05). Compared with the HDCP group, the 24-h urinary protein, Scr and BUN levels of rats in the AG490 group were lower (P<0.05). The levels of C-reactive protein (CRP), interleukin-1β (IL1β) and lipid peroxide (LPO) were lower and the levels of catalase (CAT) were higher in the AG490 group than in the HDCP group (P< 0.05). Compared with the HDCP group, the placental mass, fetal rat length, and body mass were higher in the AG490 group (P<0.05).The Ang Ⅱ level of rats in the HDCP group was (67.81±7.69) ng/L, and the NO level was (41.17±5.39) moL/L, while the Ang Ⅱ levelof rats in the AG490 group was (45.23±5.64) ng/L, and the NO level was (54.62±6.57) moL/L. Compared with the HDCP group, the ratsin the AG490 group had lower Ang Ⅱ levels and higher NO levels (P<0.05). The relative expression levels of JAK2, STAT3 and SOCS1 were lower in the AG490 group than in the HDCP group (P<0.05).Conclusion Intervention of HDCP model rats using the JAK2 inhibitor AG490 resulted in significant improvement in blood pressure levels and renal function, reduction in inflammatory response andoxidative stress in rats, improvement in fetal rat condition, elevated endothelial function in rats, and regulation of the protein expressionof the JAK2/STAT3/SOCS1 pathway. |
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