Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Braz J Med Biol Res. 2012 Jan;45(1):13-9. doi: 10.1590/s0100-879x2011007500161. Epub 2011 Dec 9.
Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.
新生 Sprague-Dawley 大鼠于生后 7 天（postnatal day 7，P7）随机分为正常对照组、轻度缺氧缺血（hypoxia-ischemia，HI）组和重度 HI 组（每组 n = 10），以研究轻度和重度 HI 对焦虑样行为和黑质（substantia nigra，SN）酪氨酸羟化酶（tyrosine hydroxylase，TH）表达的影响。轻度和重度 HI 组分别在 90 和 150 min 内暴露于缺氧（8% O2/92% N2）环境中。采用高架十字迷宫（elevated plus-maze，EPM）测试评估焦虑样行为，测量开放臂停留时间（open arms time，OAT）和开放臂百分比（open arms percentage，OAT%），免疫组织化学法测定 P14、P21 和 P28 时 SN 中 TH 的表达。EPM 中的 OAT 和 OAT%在轻度（1.88-、1.99-和 2.04-倍，1.94-、1.51-和 1.46-倍）和重度 HI 组（1.69-、1.68-和 1.87-倍，1.83-、1.43-和 1.39-倍，分别；P < 0.05）中均显著增加。SN 中 TH 阳性细胞的百分比在轻度（17.7%、40.2%和 47.2%）和重度 HI 组（16.3%、32.2%和 43.8%，分别；P < 0.05）中均显著且相似地降低。SN 中 TH 阳性细胞数量的减少和蛋白表达水平密切相关（轻度 HI 组的 Pearson 相关分析：r = 0.991，P = 0.000；重度 HI 组：r = 0.974，P = 0.000），与焦虑样行为受损有关。我们得出结论，新生 HI 导致新生 Sprague-Dawley 大鼠幼年期焦虑样行为减少，这与 SN 中 TH 活性降低有关。焦虑的损害和 TH 的表达可能不依赖于 HI 的严重程度。
