Abstract：
UNASSIGNED: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats.
METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1β (IL-1β), and cleaved caspase-3 immuno-expressions were also evaluated.
RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1β and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1β), and apoptotic (caspase-3) parameters.
CONCLUSIONS: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1β signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.
METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1β (IL-1β), and cleaved caspase-3 immuno-expressions were also evaluated.
RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1β and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1β), and apoptotic (caspase-3) parameters.
CONCLUSIONS: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1β signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.
摘要：
■胎盘功能不全是影响妊娠和胎儿生长的严重并发症。环磷酰胺(CYC)被认为是化学治疗剂之一。不幸的是,CYC不仅会影响肿瘤细胞，还会影响健康细胞，导致包括胎盘在内的多种损伤。本研究旨在评估半胱氨酰白三烯受体拮抗剂的作用；孟鲁司特（MK），CYC诱导的大鼠胎盘损伤。
方法：将48只雌性Wister大鼠随机分为8个实验组。第1组：对照妊娠组；第2组：MK5mg处理的孕鼠；第3组：MK10mg处理的孕鼠；第4组：MK20mg处理的孕鼠；第5组：孕鼠接受CYC（20mg/kg，i.p);第6组:孕鼠接受MK5mg和CYC;第7组:孕鼠接受MK10mg和CYC;第8组:孕鼠接受MK20mg和CYC。胎盘丙二醛(MDA),还原型谷胱甘肽（GSH），总抗氧化能力(TAC)，胎盘生长因子(PlGF),测定Nod样受体p3(NLRP3)炎性小体。组织学变化,白细胞介素-1β（IL-1β），和切割的caspase-3免疫表达也被评估。
结果：CYC显示胎盘GSH显著下降，TAC,和PlGF随着胎盘MDA的显着增加，NLRP3和IL-1β和caspase-3的免疫表达。MK在所有氧化应激中均显示出显着改善（MDA，GSH和TAC），炎症（NLRP3和IL-1β），和凋亡（caspase-3）参数。
结论：根据调查结果，MK可能通过抗氧化剂调节NLRP3/IL-1β信号通路在CYC诱导的胎盘损伤中发挥保护作用,抗炎,和抗凋亡作用。
方法：将48只雌性Wister大鼠随机分为8个实验组。第1组：对照妊娠组；第2组：MK5mg处理的孕鼠；第3组：MK10mg处理的孕鼠；第4组：MK20mg处理的孕鼠；第5组：孕鼠接受CYC（20mg/kg，i.p);第6组:孕鼠接受MK5mg和CYC;第7组:孕鼠接受MK10mg和CYC;第8组:孕鼠接受MK20mg和CYC。胎盘丙二醛(MDA),还原型谷胱甘肽（GSH），总抗氧化能力(TAC)，胎盘生长因子(PlGF),测定Nod样受体p3(NLRP3)炎性小体。组织学变化,白细胞介素-1β（IL-1β），和切割的caspase-3免疫表达也被评估。
结果：CYC显示胎盘GSH显著下降，TAC,和PlGF随着胎盘MDA的显着增加，NLRP3和IL-1β和caspase-3的免疫表达。MK在所有氧化应激中均显示出显着改善（MDA，GSH和TAC），炎症（NLRP3和IL-1β），和凋亡（caspase-3）参数。
结论：根据调查结果，MK可能通过抗氧化剂调节NLRP3/IL-1β信号通路在CYC诱导的胎盘损伤中发挥保护作用,抗炎,和抗凋亡作用。
