Sun Jieqiong, Zhang Huimei, Liu Fang, Tang Dongmei, Lu Xuhong
Department of Obstetrics, Zhongshan Hospital Affiliated Dalian University, Dalian, China.
Can J Physiol Pharmacol. 2018 Nov;96(11):1084-1091. doi: 10.1139/cjpp-2018-0087. Epub 2018 Jul 3.
Preeclampsia is an inflammatory disease and has connection with increased pro-inflammatory cytokines. Aspirin reduces the incidence of preeclampsia complications. However, the effects of aspirin on lipopolysaccharide-induced preeclampsia-like symptoms in rats have not been reported and the underlying molecular mechanism has not been illuminated. Hence, we investigated the anti-inflammatory effects of aspirin on lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats and elucidated the potential molecular mechanism. Preeclampsia-like phenotypes were induced by tail vein injection of lipopolysaccharide (1 μg/kg) on gestational day 14. Aspirin (2 mg/kg per day) were administered from gestational day 14 to 19. Clinical phenotypes were recorded. Placenta tissues and serum were obtained to measure inflammatory cytokines levels using ELISA kit on gestational day 20. The mRNA expressions of IL-6, IL-1β, and MCP-1 were measured by real-time PCR. Protein expressions including TLR4, MyD88, NF-κBp65, and TLR2 were determined by Western blot analysis in the rat placentas of each group. Aspirin obviously assuaged lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats. Aspirin treatment significantly decreased the levels of pro-inflammatory cytokines in serum and placenta tissues of preeclampsia rats. Aspirin also obviously downregulated the mRNA expressions of IL-6, IL-1β, and MCP-1 and assuaged the activation of TLR4, MyD88, NF-κBp65, and TLR2 in the placental tissue. Our results indicated that aspirin could assuage preeclampsia-like phenotypes, and this improvement effect is possibly the result of the suppression of pro-inflammatory cytokines via the TLR4, MyD88, NF-κBp65, and TLR2 signaling pathway.
子痫前期是一种炎症性疾病，与促炎细胞因子增加有关。阿司匹林可降低子痫前期并发症的发生率。然而，阿司匹林对脂多糖诱导的大鼠子痫前期样症状的影响尚未见报道，其潜在分子机制也未阐明。因此，我们研究了阿司匹林对脂多糖诱导的妊娠大鼠子痫前期样表型的抗炎作用，并阐明了潜在的分子机制。在妊娠第14天通过尾静脉注射脂多糖（1μg/kg）诱导子痫前期样表型。从妊娠第14天至19天给予阿司匹林（每天2mg/kg）。记录临床表型。在妊娠第20天获取胎盘组织和血清，使用ELISA试剂盒测量炎症细胞因子水平。通过实时PCR测量IL-6、IL-1β和MCP-1的mRNA表达。通过蛋白质印迹分析测定每组大鼠胎盘组织中TLR4、MyD88、NF-κBp65和TLR2的蛋白表达。阿司匹林明显缓解了脂多糖诱导的妊娠大鼠子痫前期样表型。阿司匹林治疗显著降低了子痫前期大鼠血清和胎盘组织中促炎细胞因子的水平。阿司匹林还明显下调了IL-6、IL-1β和MCP-1的mRNA表达，并缓解了胎盘组织中TLR4、MyD88、NF-κBp65和TLR2的激活。我们的结果表明，阿司匹林可以缓解子痫前期样表型，这种改善作用可能是通过TLR4、MyD88、NF-κBp65和TLR2信号通路抑制促炎细胞因子的结果。
