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电针与地塞米松干预围产期尼古丁暴露诱发子代大鼠肺发育不良的比较研究

Comparison of electroacupuncture and dexamethasone on lung development impairment in offspring rats induced by prenatal nicotine exposure

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【作者】 郭亭廷; 嵇波; 方洋; 刘翼天; 李鹤文; 刘小玄; 刘力瑜; 张玲; 刘文轩; 全烨; 马博涵; Reiko Sakurai; Virender Kumar Rehan;

【Author】 GUO Tingting;JI Bo;FANG Yang;LIU Yitian;LI Hewen;LIU Xiaoxuan;LIU Liyu;ZHANG Ling;LIU Wenxuan;QUAN Ye;MA Bohan;Reiko Sakurai;Virender Kumar Rehan;School of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine;Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA;

【通讯作者】 嵇波;

【机构】 北京中医药大学针灸推拿学院; 加州大学洛杉矶分校Harbor医学中心Lundquist生物医学创新研究所;

【摘要】 目的 观察并比较电针与地塞米松对围产期尼古丁暴露(PNE)子代大鼠肺功能、肺组织形态学及行为学的影响。方法 将24只受孕的SD母鼠按随机数字表法分为对照组、模型组、电针浅刺组和地塞米松组,每组6只。采用颈部皮下注射尼古丁制备PNE诱发子代大鼠肺发育不良模型,以子代大鼠生长指标、肺功能和肺形态与对照组比较差异有统计学意义为造模成功。从母鼠受孕第6天起,对照组颈部皮下注射0.9%氯化钠溶液(1 mg/kg,每日1次),其余各组颈部皮下注射尼古丁(1 mg/kg,每日1次);电针浅刺组在注射尼古丁的同时,电针母鼠双侧“足三里”,每日1次,每次20 min;地塞米松组在子代大鼠出生后第8天开始给予腹腔注射地塞米松,1.5 mg/kg,每日1次,共3 d,之后减量为0.75 mg/kg,每日1次,共4 d。造模成功后,每组每只母鼠按照随机数字表法留取4只子鼠。至子鼠出生后的第21天,将每组每只母鼠留取的4只子鼠按照随机数字表法,分别筛选1只进行生长指标(体质量、肺质量、肺指数)的检测;1只用于小动物肺功能机的检测以评价肺功能,观察指标为用力肺活量(FVC)、功能残气量(FRC)、动态肺顺应性(Cdyn)、呼气流量峰值(PEF)、最大吸气流量(PIF)及气道阻力(RL);1只进行HE染色法观察肺组织形态、肺泡数量及肺泡间隔平均厚度;1只进行莫里斯水迷宫实验,以评估两种干预方法对PNE诱发子代大鼠学习记忆能力的影响。结果 与对照组比较,模型组子代大鼠体质量、肺质量、肺指数,FVC、PEF、FRC、Cdyn,肺泡数量,以及水迷宫实验中穿过平台次数、目标象限停留时间百分比和目标象限运动路程百分比均明显减少(P<0.01),PIF、RL、肺泡间隔平均厚度及水迷宫实验潜伏期时长均明显增加(P<0.01)。与模型组比较,电针浅刺组与地塞米松组子代大鼠体质量、肺质量、肺指数,FVC、PEF、FRC、Cdyn值及肺泡数量均明显增加(P<0.05,P<0.01);PIF、RL及肺泡间隔平均厚度均明显降低(P<0.01);水迷宫实验中,电针浅刺组穿过平台次数、目标象限停留时间百分比和目标象限运动路程百分比与模型组相比均明显升高(P<0.01),潜伏期时长明显降低(P<0.01),而地塞米松组与模型组比较差异无统计学意义。与电针浅刺组比较,地塞米松组子代大鼠穿过平台次数、在目标象限停留时间百分比和在目标象限运动路程百分比均明显降低,潜伏期时长明显升高(P<0.01)。结论 电针和地塞米松通过改善肺组织形态和肺功能,对PNE子代大鼠肺发育均有保护作用;晚期、小剂量、短疗程使用地塞米松组PNE子代大鼠学习记忆能力较低,而电针组PNE子代大鼠学习记忆能力优于地塞米松组。

【Abstract】 Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE) rats. Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control, model, electroacupuncture shallow needling, and dexamethasone groups using the random number table method(n = 6 rats per group). A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine, and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters, lung function, and lung morphology compared to the control group. From the sixth day of maternal conception, the control group received cervicodorsal subcutaneous injection with 0.9% sodium chloride solution(1 mg/kg once per day), and the remaining groups were similarly injected with nicotine(1 mg/kg once per day). Concurrent with the nicotine injections, the electroacupuncture shallow needling group received electroacupuncture interventions at the "Zusanli"(ST 36) acupoint on both sides once a day for 20 min. In contrast, the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days), with a later dose of 0.75 mg/kg once per day for 4 days. Following successful model establishment, four offspring per rat were retained in each group using the random number table method. Until the 21st day after the birth of the offspring, using the random number table method, one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight, lung weight, and lung index; simultaneously, one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine, with the parameters of forced vital capacity(FVC), functional residual capacity(FRC), dynamic lung compliance(Cdyn), peak expiratory flow(PEF), peak inspiratory flow(PIF), and airway resistance(RL); concurrently, one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue, alveolar numbers, and mean alveolar septal thickness; additionally, one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE. Results Compared with the control group, the body weight, lung weight, lung index, FVC, PEF, FRC, Cdyn, alveolar number, platform crossing times, target quadrant time percentage, and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P < 0.01). In contrast, PIF, RL, average thickness of alveolar septa, and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P < 0.01). Compared with the model group, both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight, lung weight, lung index, FVC, PEF, FRC, Cdyn, and alveolar numbers(P < 0.05, P < 0.01), along with significant decreases in PIF, RL values, and mean alveolar septal thickness(P < 0.01). However, in the Morris water maze experiment, compared with the model group, the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P < 0.01), coupled with reduced latency period(P < 0.01), whereas the dexamethasone group showed no significant differences compared to the model group. Compared to the electroacupuncture shallow needling group, the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage, coupled with increased latency period(P < 0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function. However, offspring receiving late, small-dose, short-course dexamethasone exhibited inferior learning and memory capabilities, whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.

【基金】 国家自然科学基金面上项目(No.82174505,No.81674059);北京市自然科学基金面上项目(No.7252226)~~
  • 【文献出处】 北京中医药大学学报 ,Journal of Beijing University of Traditional Chinese Medicine , 编辑部邮箱 ,2025年08期
  • 【分类号】R245
  • 【下载频次】69
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