Tetramethylpyrazine reduces the consequences of nitric oxide inhibition in pregnant rats
Tetramethylpyrazine reduces the consequences of nitric oxide inhibition in pregnant rats
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四甲基吡嗪可减轻妊娠大鼠一氧化氮抑制的后果
DOI：
10.1002/jcp.28579
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Hua, Xiaolin
中科院分区：
文献类型：
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作者：
Gu, Shengyi;Shen, Huaxiang;Hua, Xiaolin
先兆子痫 (PE) 与围产期发病率和死亡率密切相关，我们想要研究四甲基吡嗪 (TMP) 对先兆子痫的影响。将妊娠Sprague-Dawley大鼠随机分为5组：正常妊娠组（PC）、PE组、PE+TMP 20mg/kg组、PE+TMP 40mg/kg组、PE+TMP 60mg/kg组。通过L-NAME治疗建立PE大鼠模型。分别通过尾套法和CBB试剂盒检测收缩压（SBP）和尿蛋白浓度。通过定量PCR分析关键基因的mRNA水平，并通过ELISA或蛋白质印迹测量关键基因的蛋白质水平。 TMP 降低 PE 大鼠的 SBP 和尿蛋白浓度。 TMP抑制L-NAME引起的仔鼠存活率、仔鼠体重和仔鼠/胎盘重量比的下降，并逆转L-NAME引起的胎盘组织学变化，但对胎盘重量影响不大。 PE大鼠尿液中nephrin和podocin表达增强，血清胎盘生长因子水平降低，而TMP则抑制上述现象。 TMP 抑制 L-NAME 诱导的 PE 大鼠血清和肾脏中 sFlt-1 的上调，同时下调 PE 大鼠血清、胎盘和肾脏中 IL-6 和 MCP-1 的表达。 TMP 还抑制 L-NAME 引起的胎盘 sFlt-1 和血管内皮生长因子水平的增加。此外，TMP 抑制 PE 大鼠中 CHOP 和 GRP78 的表达，并降低 p-elF2 α/elF2 α 的比值。 TMP 减轻了怀孕大鼠中 NO 抑制的后果。
Pre-eclampsia (PE) is closely associated with perinatal morbidity and mortality and we want to investigate tetramethylpyrazine (TMP)'s effects on PE. Pregnant Sprague-Dawley rats were randomly divided into five groups: normal pregnant (PC), PE, PE+TMP 20mg/kg, PE+TMP 40mg/kg, and PE+TMP 60mg/kg group. The PE rat model was established via L-NAME treatment. Systolic blood pressures (SBP) and urinary protein concentration were detected via the tail-cuff method and CBB kit, respectively. mRNA levels of key genes were analyzed via quantitative PCR and protein levels of key genes were measured by ELISA or western blot. TMP decreased SBP and urinary protein concentration of PE rats. TMP inhibited L-NAME-induced decrease in pups alive ratio, pups weight, and the ratio of pups/placenta weight and reversed L-NAME induced changes in placental histology, whereas it had little effect on placental weight. Urinary nephrin and podocin expressions were enhanced and serum placental growth factor level was decreased in PE rats, whereas TMP inhibited the above phenomena. TMP suppressed L-NAME-induced sFlt-1 upregulation in serums and kidneys of PE rats, whereas it downregulated IL-6 and MCP-1 expression in PE rats' serums, placentas and kidneys. TMP also suppressed the increase in placental sFlt-1 and vascular endothelial growth factor level caused by L-NAME. In addition, TMP inhibited CHOP and GRP78 expressions and decreased the ratio of p-elF2 alpha/elF2 alpha in PE rats. TMP attenuated the consequences of NO inhibition in pregnant rats.