川芎嗪对静脉注射油酸方法建立急性肺损伤模型大鼠肺组织的保护作用及机制(1)
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【摘 要】 目的：探讨川芎嗪(tetramethylpyrazine, TMP)对大鼠急性肺损伤(acute lung injury, ALI)时肺组织的保护作用及其可能的机制。方法：将大鼠随机分为4组：对照组(Control)、油酸组(OA)、川芎嗪处理组(TMP+OA)、地塞米松处理组(DEX+OA)。采用静脉注射油酸(oleic acid, OA)的方法建立大鼠ALI模型，检测肺组织丙二醛(malonaldehyde, MDA)含量和超氧化物歧化酶(superoxide dismutase, SOD)活性的表达变化，免疫组织化学染色技术观察肺组织中p38MAPK的表达变化。结果：与Control组相比，OA组大鼠SOD活性明显下降(P<0.05)，而MDA含量明显升高(P<0.05)；p38MAPK的阳性表达信号较Control组明显增强(P<0.05)；应用TMP和DEX后显著缓解上述变化(P<0.05)。结论：TMP是一种有效的抗氧化剂，它对急性肺损伤的保护机制可能与其抑制p38MAPK信号通路的过度激活有关。
【关键词】 川芎嗪；油酸；急性肺损伤；p38分裂原激活蛋白激酶；抗氧化
Protective effects of tetramethylpyrazine on acute
Lu1ng injury and its mechanisms in rats
【ABSTRACT】Objective: To investigate the protective effect of tetramethylpyrazine(TMP) on lung tissues during ALI in rats and its possible mechanisms. Methods: All rats were randomly divided into four groups: Control group, OA group, tetramethylpyrazine treatment (TMP+OA) group and dexamethasone treatment(DEX+OA) group. Rat model of ALI was established by intravenous injection of oleic acid(OA). Malonaldehyde(MDA) content and superoxide dismutase(SOD) activity of lung tissues were detected in each group. Lung tissues were imbedded by paraffin to observe the expression of p38MAPK by means of immunohistochemistry staining. Results: Compared with Control group, 1MDA content increased obvious in OA group(P<0.05), but SOD activity decreased significantly(P<0.05), the expression of p38MAPK increased obvious(P<0.05); the administration of TMP and DEX mitigated above changes significantly(P<0.05). Conclusion: TMP is an effective antioxidant , which relieves the inflammation in acute lung injury rats , possibly through the inhibition of p38MAPK activation.
【KEY WORDS】tetramethylpyrazine; OA; acute lung injury; p38MAPK; antioxidation
急性肺损伤(acute lung injury, ALI)是由心源性以外的各种肺内外致病因素所致的急性、进行性缺氧性呼吸衰竭。严重感染、创伤、休克等因素均可诱发，病情发展十分迅速，后期可并发多器官功能障碍，病死率高[1]，但其发病机制迄今为止尚未完全阐明。
丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)是细胞内的一类丝氨酸/苏氨酸蛋白激酶，广泛分布于细胞浆内，是真核细胞转导细胞外信号到细胞内引起细胞反应的信号转导系统之一。研究[2]表明p38MAPK在急慢性炎症的细胞应激反应中具有重要性，与ALI关系密切。抑制p38MAPK途径，能够有效的抑制炎症反应，明显的减轻机体的炎症反应[3]。现代医学研究[4]表明，川芎嗪(TMP)具有降低氧自由基水平等多种药理作用，对心脑血管疾病具有防治效果，但其对急性肺损伤的预防和治疗作用方面的研究较少 ......
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