目的 探讨川芎嗪对先兆子痫发展中滋养层细胞增殖、侵袭和迁移的影响及其作用机制。方法 用左旋硝基精氨酸甲酯建立先兆子痫动物模型，并随机分为对照组、模型组和川芎嗪组，采用苏木素-伊红染色观察胎盘组织病理学变化。人绒毛膜滋养层HTR8/SVneo细胞和人绒毛膜癌JEG3细胞给予川芎嗪干预后，采用CCK-8实验、EdU实验、Transwell实验以及划痕实验检测细胞增殖、侵袭及迁移能力；利用NCBI在线数据库（GSE165324）分析先兆子痫患者来源的人脐静脉血管内皮细胞和正常人脐静脉血管内皮细胞中前8个上调的circRNAs；qRT-PCR法检测川芎嗪对HTR8/SVneo和JEG3细胞circRNA表达的影响，以及先兆子痫患者和对照组胎盘组织中的circ_0026462表达量；利用RNase R分析circRNA稳定性。circRNA过表达后，检测川芎嗪对HTR8/SVneo和JEG3细胞增殖、侵袭及迁移能力的影响。结果 川芎嗪可以改善左旋硝基精氨酸甲酯诱导的大鼠胎盘组织细胞肿胀、空泡化增加以及炎症细胞浸润现象，并促进滋养层细胞增殖、侵袭和迁移（P＜0.05）。与对照组比较，circ_0026462在先兆子痫患者胎盘组织中高表达（P＜0.05）。川芎嗪抑制滋养层细胞中circ_0026462的表达（P＜0.05）。circ_0026462过表达抑制滋养层细胞增殖、侵袭和迁移（P＜0.05）。此外，circ_0026462过表达能够逆转川芎嗪对滋养层细胞增殖、侵袭和迁移的促进作用（P＜0.05）。结论 川芎嗪通过抑制circ_0026462的表达促进滋养层细胞增殖、侵袭和迁移。

Objective To investigate the effect and mechanism of ligustrazine on proliferation, invasion and migration of trophoblast cells during the development of preeclampsia. Methods An animal model of preeclampsia was established using L-nitroarginine methyl ester and randomly divided into control group, model group and ligustrazine group, hematoxylin eosin staining was used to observe pathological changes in placental tissue. After administering ligustrazine intervention to human trophoblast HTR8/SVneo cells and human choriocarcinoma JEG3 cells, cell proliferation, invasion and migration abilities were detected using CCK-8 assay, EdU assay, Transwell assay and scratch assay; NCBI online database (GSE165324) was used to analyze the first eight upregulated circRNAs in human umbilical vein endothelial cells from patients with preeclampsia and normal human umbilical vein endothelial cells; qRT-PCR method was used to detect the effect of ligustrazine on the expressions of circRNA in HTR8/SVneo and JEG3 cells, as well as the expression level of circ_0026462 in placental tissue of patients with preeclampsia and control group; RNase R was used to analyze the stability of circRNA. After overexpression of circRNA, the effect of ligustrazine on proliferation, invasion and migration ability of HTR8/SVneo and JEG3 cells were detected. Results Ligustrazine could improve the swelling, increased vacuolization and inflammatory cell infiltration of rat placental tissue cells induced by L-nitroarginine methyl ester, and promote the proliferation, invasion and migration of trophoblast cells (P < 0.05). Compared with control group, circ_0026462 was highly expressed in placental tissue of patients with preeclampsia (P < 0.05). Ligustrazine inhibited the expression of circ_0026462 in trophoblast cells (P < 0.05). Overexpression of circ_0026462 inhibited proliferation, invasion and migration of trophoblast cells (P < 0.05). In addition, overexpression of circ_0026462 could reverse the promoting effect of ligustrazine on proliferation, invasion and migration of trophoblast cells (P < 0.05). Conclusion Ligustrazine promotes proliferation, invasion and migration of trophoblast cells by inhibiting the expression of circ_0026462.

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