de Vries Willem B, van der Leij Feike R, Bakker Joost M, Kamphuis Patrick J G H, van Oosterhout Matthijs F M, Schipper Marguerite E I, Smid Gioia B, Bartelds Beatrijs, van Bel Frank
Department of Neonatology, University Medical Center/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Pediatr Res. 2002 Dec;52(6):900-6. doi: 10.1203/00006450-200212000-00015.
Glucocorticoid treatment in preterm babies to prevent chronic lung disease causes myocardial hypertrophy and increased myocardial protein content. Although these changes are thought to be transient, there is evidence that dexamethasone (DEX) induces permanent myocardial abnormalities as well. We investigated whether a therapeutic course of neonatal DEX in rat pups produces anatomic and biochemical alterations in rat hearts during adult life. Twenty-four rat pups were treated with DEX on d 1, 2, and 3 (0.5, 0.3, and 0.1 micro g/g) of life, with doses proportional to those used in preterm babies. Twenty-four control pups were treated with saline. At d 7, wk 8, or wk 45 (n = 8 per group) rats were killed. The anatomic parameters measured were body weight (Bw, in grams), heart (myocardial) weight (Hw, in milligrams), and the Hw:Bw ratio. Myocardial total protein (Prot) and DNA content were determined, and the Prot:DNA ratio was calculated. Histopathology and morphometry were performed on 45-wk-old rat hearts. In DEX-treated rat pups, at d 7, Bw and Hw were lower and the Hw:Bw ratio was increased. DNA content was lower, Prot higher, and Prot:DNA ratio was increased. In 8-wk-old rats Bw, Hw, DNA content, Prot content or Prot:DNA ratio did not differ between groups, but the Prot:DNA ratio still tended to be higher in DEX-treated rats. In 45-wk-old rats Hw and Hw:Bw ratio were significantly lower and Prot:DNA ratio higher in DEX-treated rats. Histopathologic analysis showed larger cardiomyocyte volume, length, and width, indicating hypertrophy, and increased collagen, indicating early degeneration of individual myocytes. In conclusion, neonatal DEX treatment in rat pups causes a permanent decrease in heart weight, as well as hypertrophy and early degeneration of cardiomyocytes during adulthood.
早产儿使用糖皮质激素治疗以预防慢性肺病会导致心肌肥大和心肌蛋白含量增加。尽管这些变化被认为是暂时的，但有证据表明地塞米松（DEX）也会诱发永久性心肌异常。我们研究了新生大鼠幼崽接受一个疗程的新生儿DEX治疗后，成年期大鼠心脏是否会出现解剖学和生化改变。24只大鼠幼崽在出生第1、2、3天接受DEX治疗（剂量分别为0.5、0.3和0.1μg/g），剂量与早产儿使用的剂量成比例。24只对照幼崽接受生理盐水治疗。在第7天、第8周或第45周（每组n = 8）处死大鼠。测量的解剖学参数包括体重（Bw，克）、心脏（心肌）重量（Hw，毫克）以及Hw:Bw比值。测定心肌总蛋白（Prot）和DNA含量，并计算Prot:DNA比值。对45周龄大鼠心脏进行组织病理学和形态计量学分析。在接受DEX治疗的大鼠幼崽中，第7天时，Bw和Hw较低，Hw:Bw比值升高。DNA含量较低，Prot较高，Prot:DNA比值升高。在8周龄大鼠中，两组之间的Bw、Hw、DNA含量、Prot含量或Prot:DNA比值没有差异，但接受DEX治疗的大鼠中Prot:DNA比值仍有升高趋势。在45周龄大鼠中，接受DEX治疗的大鼠Hw和Hw:Bw比值显著较低，Prot:DNA比值较高。组织病理学分析显示心肌细胞体积、长度和宽度增大，表明存在肥大，胶原蛋白增加，表明单个心肌细胞早期变性。总之，新生大鼠幼崽接受新生儿DEX治疗会导致成年期心脏重量永久性降低，以及心肌细胞肥大和早期变性。
