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前列腺素E1对高氧诱导新生大鼠脑损伤的保护作用
Protective effect of prostaglandin E1 against brain injury induced by hyperoxia in neonatal rats
目的 探讨前列腺素E1（PGE-1）对高氧诱导新生大鼠脑损伤的保护作用，并观察糖调节蛋白78（GRP78）、CHOP蛋白表达的变化，为临床应用PGE-1治疗高氧引起的新生儿脑损伤提供理论依据。方法 将60只新生Wistar大鼠随机分成空气对照组、高氧脑损伤模型组和高氧脑损伤+PGE-1组。除空气对照组外均制备高氧脑损伤模型，从造模第1天起，高氧脑损伤+PGE-1组腹腔注射PGE-1，剂量为每日2 μg/kg，连续7 d，其他两组以生理盐水替代。检测各组大鼠脑组织含水量，苏木精-伊红染色观察脑组织病理变化，核染色结合TUNEL染色观察脑细胞凋亡情况，Western blot法检测脑组织GRP78、CHOP蛋白水平。结果 高氧脑损伤模型组脑组织含水量高于高氧脑损伤+PGE-1组及空气对照组（P < 0.05）；高氧脑损伤+PGE-1组脑组织含水量高于空气对照组（P < 0.05）。脑组织病理切片结果显示：高氧脑损伤模型组大鼠脑实质可见炎症细胞浸润增多，轻度脑血管水肿；高氧脑损伤+PGE-1组大鼠脑实质周围炎症及水肿较高氧脑损伤模型组减轻。高氧脑损伤模型组脑组织细胞凋亡指数高于高氧脑损伤+PGE-1组及空气对照组（P < 0.05）；高氧脑损伤+PGE-1组脑组织细胞凋亡指数高于空气对照组（P < 0.05）。高氧脑损伤模型组脑组织GRP78、CHOP蛋白的相对表达高于高氧脑损伤+PGE-1组和空气对照组（P < 0.05）；高氧脑损伤+PGE-1组GRP78、CHOP蛋白的相对表达高于空气对照组（P < 0.05）。结论 PGE-1对高氧诱导脑损伤新生大鼠具有保护作用，其机制可能为通过下调GRP78、CHOP蛋白表达，从而抑制细胞凋亡。
Objective To investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia. Methods Sixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group. All rats except those in the air control group were treated to establish a hyperoxic brain injury model. From the first day of modeling, the rats in the hyperoxia brain injury+PGE-1 group were intraperitoneally injected with PGE-1 2 μg/kg daily for 7 consecutive days, while the other two groups were treated with normal saline instead. The water content of brain tissue was measured; the pathological changes of brain tissue were evaluated by hematoxylin-eosin staining; the apoptosis of brain cells was assessed by nuclear staining combined with TUNEL staining; the protein expression of GRP78 and CHOP in brain tissue was measured by Western blot. Results The water content of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the water content of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P < 0.05). The pathological section of brain tissue showed inflammatory cell infiltration and mild cerebrovascular edema in the brain parenchyma in the hyperoxic brain injury model group; the periparenchymal inflammation and edema in the hyperoxic brain injury+PGE-1 group were milder than those in the hyperoxic brain injury model group. The apoptosis index of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the apoptosis index of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P < 0.05). The protein expression of GRP78 and CHOP in brain tissue was significantly higher in the hyperoxic brain injury model group than in the hyperoxic brain injury+PGE-1 group and air control group (P < 0.05); the protein expression of GRP78 and CHOP was significantly higher in the hyperoxic brain injury+PGE-1 group than in the air control group (P < 0.05). Conclusions PGE-1 has a protective effect against hyperoxia-induced brain injury in neonatal rats, which may be related to the inhibition of cell apoptosis by down-regulating the expression of GRP78 and CHOP.
前列腺素E1 / 高氧脑损伤 / 糖调节蛋白78 / CHOP蛋白 / 新生大鼠
Prostaglandin E1 / Hyperoxic brain injury / Glucose-regulated protein 78 / CHOP / Neonatal rats
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国家自然科学基金（81160083）。
