汉防己甲素对大鼠先天性膈疝模型胎仔肺发育影响的电镜观察

Effect of tetrandrine on lung development:experiment of nitrofen-induced congenital diaphragmatic hernia fetal rat model

目的探讨产前应用汉防己甲素(TET)对先天性膈疝(CDH)大鼠模型肺发育不良的影响。方法 6只雌性 SD 大鼠孕后9.5 d 随机分为对照组、膈疝组和治疗组,各2只。膈疝组和治疗组给予除草醚125 mg/只灌胃,对照组给予等量食用花生油。11.5 d,治疗组给予30 mg/kg TET 灌胃(1次/d,连续3 d),膈疝组和对照组给予等量生理盐水。第21天剖宫取出胎鼠两侧肺组织,记录胎鼠膈疝形成情况,分别用光镜和透射电镜进行组织学观察,并对Ⅱ型肺上皮细胞进行记数和比较。结果膈疝组与治疗组共32只胎鼠有膈疝形成,致畸率为78%(32/41),两组之间致畸率差异无统计学意义(P=0.645)。光镜与透射电镜观察下可见膈疝组无论在组织结构还是细胞亚微结构方面均存在肺发育不良,其发育明显滞后于正常对照组,通过 TET 治疗后的治疗组肺发育较膈疝组成熟,形态结构接近于正常对照组。各组Ⅱ型肺上皮细胞数量差异无统计学意义(P=0.779)。结论产前应用 TET 干预治疗对 CDH 大鼠肺发育不良具有明显的改善作用,使其肺内结构无论在组织结构还是细胞结构上,都更接近于成熟形态。故产前应用 TET 可促进 CDH 大鼠胎肺发育,为临床治疗CDH 提供新的思路。

Objective To assess the efficacy of prenatal administration of tetrandrine （TET） on pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia （CDH） fetal rat model. Methods Six timed-pregnant female Sprague-Dawley rats were randomly divided into 3 equal groups： CDH group （ receiving gavage of nitrofen 125 mg dissolved in seed fat on day 9.5 ）, and TET group （ receiving gavage of nitrofen 125 mg on day 9.5 and then gavage of TET 3 0 mg/kg on days 11.5-14. 5）, and control group （ given the same dose of peanut oil on day 9.5 and the same dose of normal saline on days 11.5- 14.5）. The fetuses were delivered by cesarean section on day 21 to undergo light microscopy and electron microscopy. The numbers of type Ⅱ pneumocytes were recorded and compared. Results CDH were detected in 32 of the 41 fetuses from the CDH and TET groups with a teratogenic rate of 78% , however, without a significant difference between the CDH and TET groups （P = 0. 645 ）. Microscopy showed significant lung hypoplasia in both histologic structure and cellular structure in the CDH group; however the lung development of the TET group was improved in comparison to the CDH group. There was no significant difference in numbers of type Ⅱ pneumocytes among the 3 groups （ P = 0. 779 ）. Conclusion Prenatal administration of TET can improve the lung development of CDH rats in both histological structure and cellular structure. This may provide a new idea for the clinical treatment of CDH.