Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model
Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model
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环孢素 A 通过减少子痫样大鼠模型中的全身炎症来改善子痫发作
DOI：
10.1038/s41440-019-0387-3
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发表时间：
2020-01-14
影响因子：
5.4
通讯作者：
Liu, Huishu
中科院分区：
文献类型：
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作者：
Huang, Qian;Hu, Bihui;Liu, Huishu
我们之前的研究表明，先兆子痫的母体高炎症反应降低了子痫样癫痫发作阈值。环孢素 A (CsA) 是一种有效的免疫抑制剂，可以减轻 LPS 诱导的先兆子痫大鼠的炎症反应。在这里，我们假设 CsA 可能通过减少先兆子痫/子痫的全身炎症来改善癫痫发作的严重程度。在当前的研究中，在先兆子痫模型中检查了 CsA 对先兆子痫表现、子痫样癫痫发作活动和全身炎症的影响。孕鼠尾静脉注射脂多糖后腹腔注射致痫药物戊四氮（PTZ），建立子痫样癫痫模型。 LPS输注后通过尾部静脉内施用CsA(5mg/kg)。检测先兆子痫的平均收缩压和蛋白尿。注射 PTZ 后，评估癫痫发作活动，确定炎症反应并分析妊娠结局。结果显示，CsA治疗显着降低血压和蛋白尿，增加胎儿和胎盘重量（P<0.01）。同时，CsA治疗显着降低血清IL-1β、TNF-α和IL-17水平（P<0.01），降低癫痫评分并延长癫痫潜伏期（P<0.01）。 CsA 有效减轻先兆子痫的表现和子痫样癫痫发作的严重程度。此外，CsA 治疗可显着降低炎症细胞因子水平并改善子痫样癫痫发作后的妊娠结局。先兆子痫中炎症细胞因子的减少与CsA治疗后先兆子痫表现的减弱相一致，表明CsA治疗可能通过减少先兆子痫/子痫的全身炎症来降低子痫样癫痫发作的严重程度。
Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P< 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P< 0.01), decreased the seizure scores and prolonged the latency to seizure (P< 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.