Effects of tetramethylpyrazine on vascular endothelial growth factor expression in hyperoxic lung injury of neonatal rats

Abstract

Abstract: Objective To study the expression of vascular endothelial growth factor in hyperoxia induced lung injury in newborn rats and to observe the interfering effect of tetramethylpyrazine (TMP) on it. Methods A total of 96 clean Sprague-Dawley(SD) rats which were less than 12 hours old were enroled in this study.The neonatal rats were randomly divided into 4 groups:Ⅰ:air-exposedcontrol group;Ⅱ:air-exposed+TMP-treated group;Ⅲ:hyperoxia-exposed control group;Ⅳ:hyperoxia-exposed+TMP-treated group.The rats were sacrificed at postnatal days 3,7,14 ( 8 rats each time point) and their lungs were collected.the lung histophatholoical changes were observed by HE staining;The protein expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial growth factor (VEGF) were performed by immunostaining.Capillary density was quantified by measuring the area of PECAM-1 immunostaining in proportion to the total area of parenchymal cells.Results At 3 d,7 d,14 d of the exposure,group Ⅲ(treatment of hyperoxia-exposed rats) resulted in a significant decrease in RAC and Capillary density.The expressions of VEGF and CD-31 protein after 3,7,14 days of hyperoxia exposure decreased significantly in the group Ⅲ compared with group Ⅰ、Ⅱand Ⅳ(P<0.05).Lung pathologic changes (RAC and Capillary density )and the expression of VEGF and CD-31in group Ⅳwere similar to those in group ⅠandⅡ (P>0.05). Conclusion Hyperoxia exposure inhibited the expression of lung VEGF in neonatal rats.Treatment with TMP during hyperoxia exposure is associated with improved alveolar structure.the potential mechanism might be that TMP can up regulates the expressions of VEGF in lung tissue.

Key words: tetramethylpyrzeine, vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1, hyperoxia, lung, neonate rats

摘要： 目的探讨高氧性肺损伤新生大鼠肺损伤过程中血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达情况,并观察川芎嗪对高氧性肺损伤的干预作用。方法 96只出生12 h内的清洁级Sprague-Dawley(SD)大鼠作为研究对象。随机分成4组(每组24只):Ⅰ组:空气对照组;Ⅱ组:空气+川芎嗪组;Ⅲ组:高氧组;Ⅳ组:高氧+川芎嗪组。Ⅲ组、Ⅳ组新生大鼠高氧暴露(氧体积分数850 mL/L),Ⅱ组、Ⅳ组予每日腹腔注射溶于9 g/L盐水的川芎嗪30 mg/kg,Ⅰ组、Ⅲ组予等量9 g/L盐水注射。在实验3、7 d和14 d每组随机选取8只处死,取其肺组织,采用HE染色观察其肺组织病理改变,免疫组织化学方法检测其血小板内皮细胞表面黏附分子-1(platelet endothelial cell adhesion molecule-1,PECAM-1)及VEGF水平的表达,以PECAM-1阳性染色的内皮细胞面积与肺实质细胞总面积的百分比代表肺微血管密度。结果第3,7,14天Ⅲ组RAC值及微血管密度较Ⅰ组、Ⅱ组、Ⅳ组均减少(P<0.05)。Ⅲ组新生大鼠第3,7,14 d时肺组织PECAM-1及VEGF蛋白表达明显低于Ⅰ组、Ⅱ组、Ⅳ组。Ⅳ组新生大鼠第3,7,14 d时肺组织RAC值、肺微血管密度、PECAM-1及 VEGF蛋白表达和Ⅰ组、Ⅱ组比较差异无统计学意义(P>0.05)。结论高氧暴露抑制新生鼠肺VEGF的表达,川芎嗪可改善肺发育,作用机制可能与上调VEGF的表达有关。

关键词: 川芎嗪, 血管内皮生长因子, 血小板内皮细胞表面黏附分子-1, 高氧, 肺, 新生大鼠

CLC Number:

Q95-33

LI Yin-fang,ZHANG-Li. Effects of tetramethylpyrazine on vascular endothelial growth factor expression in hyperoxic lung injury of neonatal rats[J]. journal1, 2013, 21(9): 945-949.

郦银芳,张莉. 川芎嗪对高体积分数氧肺损伤新生大鼠血管内皮生长因子表达的影响[J]. 中国儿童保健杂志, 2013, 21(9): 945-949.

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