谷氨酰胺影响脓毒症大鼠脑内PDGF及其受体表达的研究

Effects of glutamine on platelet-derived growth factor and its receptor following septic brain damage in rats

摘要:

目的：该研究旨在探讨脓毒症幼年大鼠大脑血小板衍生生长因子-B（PDGFB）及其受体(PDGFR-β)表达的变化及谷氨酰胺（Gln）干预的影响，探讨PDGF-B在幼年期脓毒症时脑损伤发病机制中的作用及Gln对脑损伤的可能保护机制。方法：120只10日龄Wistar大鼠随机分为对照组、内毒素组（LPS）和谷氨酰胺组（Gln）。腹腔注射内毒素（LPS，5 mg/kg)制备幼年大鼠脓毒症动物模型。Gln组为腹腔注射LPS前1 h腹腔注射Gln (1.346 g/kg)。各组大鼠又分为5个亚组（n=8），分别于注射后2、6、12、24及72 h处死，采用免疫组织化学方法及免疫印迹法检测大脑皮层PDGF-B及PDGFR-β的表达。结果：（1）免疫组织化学方法结果显示注射LPS后 72 h Gln组大脑皮层神经元PDGF-B和 PDGFR-β表达明显高于对照组和LPS组。（2）免疫印迹方法结果显示，LPS组和Gln组于注射LPS后第2 h、6 h和12 h 的PDGF-B表达均低于对照组（P＜0.05）。而Gln组12 h和72 h 的PDGF-B表达明显高于LPS组（P＜0.05）。与对照组比较，LPS组大脑组织PDGFR-β表达在2 h和6 h增加，而在72 h表达下降（P＜0.05）。Gln组则与对照组于各时间点比较，差异均无统计学意义。结论：Gln在注射LPS后能上调大脑PDGF-B和PDGFR-β的表达，提示Gln对幼年期脓毒症脑损伤的保护机制可能与其促进大脑PDGF-B和PDGFR-β的表达有关。［中国当代儿科杂志，2010，12(12)：967-971］

Abstract:

OBJECTIVE: This study investigated the expression of platelet-derived growth factor-B (PDGF-B) and its receptor-β (PDGFR-β) in rat cerebral cortex following sepsis and explored the possible underlying mechanism of neuro-protective effect of glutamine (Gln). METHODS: One hundred and twenty 10-day-old Wistar rats were randomly divided into three groups: a control group that received an intraperitoneal injection of normal saline (1 mL/kg), a sepsis group that received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg), and a Gln treatment group that was administered with Gln (1.346 g/kg) 1 hr before LPS injection. The rats were subdivided into 5 groups sacrificed at 2, 6, 12, 24 and 72 hrs after LPS or normal saline injection (n=8). The distribution and expression of PDGF-B and PDGFR-β in the cerebral cortex were ascertained by immunohistochemistry and Western blot. RESULTS: The immunohistochemistry results showed that the PDGF-B and PDGFR-β expression in the cerebral cortex increased significantly in the Gln treatment group 72 hrs after LPS injection compared with that in the control and the sepsis groups. The Western blot results showed that the PDGF-B expression in the brain tissue in the sepsis and the Gln treatment groups were significantly lower than that in the control group 2, 6, and 12 hrs after LPS injection, while the Gln treatment group had increased PDGF-B expression compared with the sepsis group 12 and 72 hrs after LPS injection. Compared with the control group, the PDGFR-β expression in the brain tissue in the sepsis group increased 2 and 6 hrs after LPS injection but decreased significantly 72 hrs after LPS injection. There were no significant differences in the PDGFR-β expression between the Gln treatment and the control groups at all different time points. CONCLUSIONS: Gln can increase the PDGF-B and PDGFR-β expression in the brain tissue of rats with sepsis. The increased PDGF-B and PDGFR-β expression might contribute to neuro-protective effects of Gln.［Chin J Contemp Pediatr, 2010, 12 (12):967-971］