低强度脉冲超声促进子宫复旧：临床疗效和机制见解的前瞻性多中心研究。
完整摘要 · 中文译文
目的：评估低强度脉冲超声（LIPUS）在促进产后子宫复旧及减轻产后并发症方面的临床疗效和安全性，并通过体外和体内实验动物模型探讨其分子作用机制。 方法：这项多中心、随机、双盲、对照试验于2023年1月至2024年12月在中国三个中心进行。受试者被随机分配至低强度脉冲超声（LIPUS）组或对照组。LIPUS组接受频率0.8 MHz、空间峰值时间平均强度2.0 W/cm2、焦域面积0.09-0.12 cm2、脉冲持续时间4 ms的治疗，每天30 min，连续10天，于产后2 h开始。对照组接受参数相同但无声输出的假治疗。主要结局指标，即治疗后第10天经腹三维超声测量的子宫体积下降百分比，在两组间进行比较。次要结局指标，包括产后并发症（继发性产后出血和产褥感染）的发生率、恶露持续时间及子宫复旧指标（宫底高度下降指数和子宫径线）也进行了比较。在体内实验中，对接受LIPUS或假治疗处理的产后Sprague-Dawley大鼠子宫组织，采用苏木精-伊红染色评估形态学，并采用免疫组织化学和蛋白质印迹法评估内皮素-1（ET-1）和催产素受体（OTR）蛋白的分布并定量其表达。在体外实验中，来自未经处理大鼠的子宫组织条在离体条件下接受LIPUS或假处理，使用BL-420F生物信号采集系统测量收缩力。来自未经处理大鼠的原代子宫平滑肌细胞（USMCs） 细胞在体外暴露于低强度脉冲超声（LIPUS）或假照射，然后通过荧光成像和流式细胞术评估细胞内钙离子（Ca2+），并通过蛋白质印迹法评估ET-1和OTR的表达。为评估钙通道的参与，在收缩性和流式细胞术实验中加入了硝苯地平（一种L型钙通道拮抗剂），设立了四个处理组：对照组、单独LIPUS组、单独硝苯地平组以及LIPUS+硝苯地平组。对于体内和体外实验，在LIPUS处理组和对照组之间比较结果；对于收缩性和流式细胞术测定，在所有四个组之间进行比较。 结果：总共纳入了1106名受试者，其中553名被随机分配到对照组，553名分配到低强度脉冲超声（LIPUS）组。排除后，LIPUS组528名女性和对照组530名女性纳入了最终分析。与对照组相比，接受LIPUS治疗的参与者的子宫体积减少百分比和宫底高度下降指数显著更大，恶露持续时间更短，子宫各径线减小，继发性产后出血和产褥感染的发生率更低（均P < 0.05）。体外实验表明，LIPUS与大鼠子宫肌条收缩力增加以及子宫平滑肌细胞（USMCs）内Ca2+水平升高显著相关（P < 0.001）；这些效应被硝苯地平减弱，但被LIPUS部分恢复。与对照组相比，LIPUS处理的子宫组织和USMCs中内皮素-1（ET-1）和催产素受体（OTR）的表达水平也显著更高（P < 0.05）。 结论：LIPUS的应用与子宫体积减小和产后并发症减少显著相关，表明其具有促进子宫复旧的潜力。这种效应可能通过增强Ca2+内流和上调USMCs中ET-1和OTR的表达来介导。这些发现支持LIPUS作为一种改善产后结局的非侵入性方法的潜力。© 2026 国际妇产科超声学会。
完整摘要 · 英文原文
OBJECTIVE: To assess the clinical efficacy and safety of low-intensity pulsed ultrasound (LIPUS) in facilitating uterine involution after delivery and mitigating postpartum complications, and to explore its molecular mechanisms of action through both in-vitro and in-vivo experimental animal models. METHODS: This multicenter, randomized, double-blind, controlled trial was conducted across three centers in China from January 2023 to December 2024. Participants were randomized to a LIPUS group or a control group. The LIPUS group received treatment at 0.8 MHz with a spatial peak-temporal average intensity of 2.0 W/cm2, focal area of 0.09-0.12 cm2 and pulse duration of 4 ms, for 30 min daily over 10 consecutive days, starting 2 h after delivery. The control group received sham treatment with identical parameters but no acoustic output. The primary outcome, percentage reduction in uterine volume on post-treatment day 10, measured using transabdominal three-dimensional ultrasonography, was compared between the two groups. Secondary outcomes, including the incidence of postpartum complications (secondary postpartum hemorrhage and puerperal infection), duration of lochia and indices of uterine involution (fundal height descent index and uterine dimensions) were also compared. For in-vivo experiments, uterine tissues from postpartum Sprague-Dawley rats that had undergone LIPUS or sham treatment were evaluated using hematoxylin and eosin staining for morphology, and immunohistochemistry and Western blotting to assess distribution of endothelin-1 (ET-1) and oxytocin receptor (OTR) proteins and to quantify their expression. For in-vitro experiments, uterine tissue strips from untreated rats were exposed to LIPUS or sham treatment ex vivo for contractility measurement using a BL-420F biological signal acquisition system. Primary uterine smooth-muscle cells (USMCs) from untreated rats were exposed to LIPUS or sham irradiation in vitro and assessed for intracellular calcium ions (Ca2+) by fluorescence imaging and flow cytometry, and for ET-1 and OTR expression by Western blotting. To assess calcium-channel involvement, nifedipine (an L-type calcium-channel antagonist) was included in the contractility and flow cytometry experiments, establishing four treatment groups: control, LIPUS alone, nifedipine alone and LIPUS + nifedipine. For in-vivo and in-vitro experiments, results were compared between the LIPUS-treated and control groups; for the contractility and flow cytometry assays, comparisons were made among all four groups. RESULTS: In total, 1106 participants were enrolled, with 553 assigned randomly to the control group and 553 to the LIPUS group. After exclusions, 528 women in the LIPUS group and 530 in the control group were included in the final analysis. Compared with controls, the LIPUS-treated participants showed a significantly greater percentage reduction in uterine volume and fundal height descent index, shorter lochia duration, reduced uterine dimensions and a lower incidence of secondary postpartum hemorrhage and puerperal infection (all P < 0.05). In-vitro experiments demonstrated that LIPUS was significantly associated with increased contractility of rat uterine tissue strips and elevated intracellular Ca2+ levels in USMCs (P < 0.001); these effects were attenuated by nifedipine but partially restored by LIPUS. Expression levels of ET-1 and OTR were also significantly higher in LIPUS-treated uterine tissue and USMCs compared with controls (P < 0.05). CONCLUSIONS: LIPUS application is significantly associated with reduced uterine volume and fewer postpartum complications, suggesting its potential to promote uterine involution. This effect may be mediated through enhanced Ca2+ influx and upregulation of ET-1 and OTR in USMCs. These findings support the potential of LIPUS as a non-invasive approach to improve postpartum outcomes. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.