Effect of nicotine on placental inflammation and apoptosis in preeclampsia-like model
Effect of nicotine on placental inflammation and apoptosis in preeclampsia-like model
复制标题
尼古丁对子痫前期模型胎盘炎症和细胞凋亡的影响
DOI：
10.1016/j.lfs.2020.118314
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发表时间：
2020-11-15
期刊：
影响因子：
6.1
通讯作者：
Liu, Huishu
中科院分区：
文献类型：
--
作者：
Li, Xin;Zhou, Bei;Liu, Huishu
目的：采用子痫前期（PE）患者的胎盘组织和脂多糖（LPS）诱导的PE样模型，研究PE中胎盘炎症和细胞凋亡的意义。主要方法：采用TUNEL染色法检测PE患者和PE样大鼠模型的胎盘细胞凋亡。免疫荧光染色检测PE患者胎盘组织中CD 68（+）巨噬细胞数量的变化。促炎细胞因子肿瘤坏死因子α mRNA的表达（TNF-α），白细胞介素通过qRT-PCR测定PE样模型中的IL-1 β、MCP-1和参与外源性或内源性凋亡信号传导的蛋白;免疫荧光染色用于检测TNF-α受体（TNFR 1）、MCP-1和凋亡相关蛋白的表达。PE组和PE样模型组胎盘细胞凋亡均明显增加，PE组胎盘内巨噬细胞浸润明显增多。与对照组相比，PE样大鼠中TNF-α、IL-1 β、MCP-1和caspase 3、caspase 8、caspase 9的mRNA表达显著上调，胎盘MCP-1、TNFR 1和胎盘凋亡相关蛋白的免疫反应性显著降低。（半胱天冬酶3、半胱天冬酶8、半胱天冬酶9、Bax）也增强;尼古丁处理显著逆转了这些变化。我们的数据表明，尼古丁的保护作用与抑制胎盘炎症和细胞凋亡有关，尼古丁可能是预防先兆子痫的潜在治疗候选药物。
Aims: Placental tissues from patients with preeclampsia (PE) and in the lipopolysaccharide (LPS)-induced PE-like model were used to investigate the implication of placental inflammation and apoptosis in PE. Whether the beneficial effects of nicotine are related to inhibition of placental inflammation and apoptosis in the PE-like model were investigated.Main methods: Placental apoptosis was detected in PE patients and the PE-like rat model by TUNEL staining. Changes in the number of CD68(+) macrophages in placental tissues from PE patients were detected by immunofluorescent staining. The mRNA expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin (IL-1 beta), MCP-1, and proteins involved in extrinsic or intrinsic apoptosis signaling in the PElike model was determined by qRT-PCR; immunofluorescent staining was used to detect the expression of TNF-alpha receptor (TNFR1), MCP-1 and apoptosis-related proteins.Key findings: Placental apoptosis was increased in both PE patients and the PE-like model, more macrophages infiltrated into placenta in PE patients. A significant upregulation in mRNA expression of TNF-alpha, IL-1 beta, MCP-1, and caspase 3, caspase 8, caspase 9 was found in the PE-like rats compared to the control animals, the immunoreactivity of placental MCP-1, TNFR1, and apoptosis-related proteins (caspase 3, caspase 8, caspase 9, Bax) was also enhanced; nicotine treatment significantly reversed those changes.Significance: Our data suggests that the protective effects of nicotine are associated with inhibiting placenta inflammation and apoptosis, and nicotine might be a potentially therapeutic candidate for preventing preeclampsia.