LncRNA-NEAT1对妊娠期高血压大鼠JAK2/STAT3信号通路、炎症反应和妊娠结局的影响

Effects of LncRNA-NEAT1 on JAK2/STAT3 Signaling Pathway,Inflammatory Response and Pregnancy Outcome in Hypertensive Rats during Pregnancy

目的:探讨LncRNA-NEAT1对妊娠期高血压大鼠JAK2/STAT3信号通路、炎症反应和妊娠结局的影响。方法:采用注射L-精氨酸甲酯的方法构建妊娠期高血压大鼠模型。采用Western blot检测JAK2/STAT3信号通路蛋白表达;采用ELISA法检测炎症因子和血管内皮损伤因子。观察并记录大鼠24 h蛋白尿、尾静脉压和死胎率。结果:与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组JAK2、STAT3的蛋白表达水平明显更高(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和s ICAM-1水平明显更高,而NO水平明显更低(P<0.05);与模型组相比,LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和s ICAM-1水平明显更高(P<0.05),而NO水平明显更低(P<0.05),而LncRNA-NEAT1过表达组ET-1和s ICAM-1表达水平明显更高,而NO明显更低(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组TNF-α、IL-1β、IL-18表达水平明显更高(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组尾静脉压和24h蛋白尿水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组尾静脉压和24 h蛋白尿表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组尾静脉压和24 h蛋白尿表达水平明显更高(P<0.05);LncRNA-NEAT1过表达组(21.56%)死胎率显著高于模型组(16.72%)和LncRNA-NEAT1抑制组(5.65%)。结论:妊娠期糖尿病大鼠LncRNA-NEAT1的表达下调可抑制JAK2/STAT3信号通路的表达并下调下游促炎因子的表达,进而缓解血管内皮损伤降低死胎率。

Objective:To investigate the effects of LncRNA-NEAT1 on JAK2/STAT3 signaling pathway,inflammatory response and pregnancy outcome in hypertensive rats during pregnancy.Methods:The hypertensive rat model of pregnancy was established by injecting L-arginine methyl ester.The protein expression of JAK2/STAT3 signaling pathway was detected by Western blot.Inflammatory factors and vascular endothelial injury factors were detected by ELISA.Proteinuria,caudal venous pressure and stillbirth rate were observed and recorded.Results:Compared with blank group,the protein expression levels of JAK2 and STAT3 in model group,LncRNA-NEAT1 overexpression group and LncRNA-NEAT1 inhibition group were significantly higher(P<0.05).Compared with model group,the protein expression levels of JAK2 and STAT3 in LncRNA-NEAT1 inhibition group were significantly lower(P<0.05),while the protein expression levels of JAK2 and STAT3 in LncRNA-NEAT1 overexpression group were significantly higher(P<0.05).Compared with blank group,the levels of ET-1 and sICAM-1 in model group,LncRNA-NEAT1 overexpression group and LncRNA-NEAT1 inhibition group were significantly higher,while the level of NO was significantly lower(P<0.05).Compared with model group,the levels of ET-1 and sICAM-1 in LncRNA-NEAT1 overexpression group and LncRNA-NEAT1 inhibition group were significantly higher(P<0.05),while the level of NO was significantly lower(P<0.05).The expression levels of ET-1 and sICAM-1 in LncRNA-NEAT1 overexpression group were significantly higher,but NO was significantly lower(P<0.05).Compared with blank group,the expression levels of TNF-α,IL-1βand IL-18 in model group,LncRNA-NEAT1 overexpression group and LncRNA-NEAT1 inhibition group were significantly higher(P<0.05).Compared with model group,the expression levels of TNF-α,IL-1βand IL-18 in LncRNA-NEAT1 inhibition group were significantly lower(P<0.05),while the expression levels of TNF-α,IL-1βand IL-18 in LncRNA-NEAT1 overexpression group were significantly higher(P<0.05).Compared with blank group,caudal venous pressure and 24 h proteinuria levels in model group,LncRNA-NEAT1 overexpression group and LncRNA-NEAT1 inhibition group were significantly higher(P<0.05).Compared with model group,the caudal venous pressure and 24 h proteinuria expression levels in LncRNA-NEAT1 inhibited group were significantly lower(P<0.05),while the caudal venous pressure and 24 h proteinuria expression levels in LncRNA-NEAT1 overexpression group were significantly higher(P<0.05).The stillbirth rate of LncRNA-NEAT1 overexpression group(21.56%)was higher than that of model group(16.72%)and LncRNA-NEAT1 inhibition group(5.65%).Conclusions:Down-regulation of LncRNA-NEAT1 in gestational diabetes rats can inhibit the expression of JAK2/STAT3 signaling pathway and down-regulate the expression of downstream pro-inflammatory factors,so as to alleviate vascular endothelial injury and reduce the stillbirth rate.