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[丝裂原活化蛋白激酶信号转导通路抑制剂U0126对油酸诱导的大鼠急性肺损伤模型Ⅱ型肺泡上皮细胞水通道蛋白4表达的影响]

[Effect of MAPK signal transduction pathway inhibitor U0126 on aquaporin 4 expression in alveolar type II cells in rats with oleic acid-induced acute lung injury].

作者信息

Chen Chun-ling, Li Tao-ping, Zhu Li-hua

机构信息

Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Aug;29(8):1525-8.

Abstract

OBJECTIVE

To investigate the relationship between aquaporin 4 (AQP4) in alveolar type II (AT-II) cells and MAPK signaling pathway in rats with early-stage oleic acid-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

METHODS

Three groups of rats, namely the normal control, ALI and U0126 treatment group were used in this study. After oleic acid-induced ALI in the latter two groups, the rats in the treatment group received 100 micromol/L U0126 treatment at the dose of 10 micro, and dimethyl sulfoxide (DMSO) were given in the normal control and ALI groups. Arterial blood gas and the extravascular lung water (EVLW) content were measured after the treatments, and pathological changes in the lung tissues were observed microscopically. ATII cells were isolated from the lung tissues and identified using tannic acid staining and alkaline phosphatase (APK) staining. The expression of AQP-4 mRNA in the cells was detected with RT-PCR.

RESULTS

Blood gas analysis, HE staining and EVLW content measurement revealed severer injury of the lung tissues in ALI group than in the normal control group, but the severity was comparable between the treatment and ALI groups. RT-PCR demonstrated significantly increased AQP-4 mRNA expression in ALI group as compared with that in the normal control group, and U0126 treatment resulted in obvious reduction in AQP-4 mRNA expression in the U0126 treatment group.

CONCLUSION

Oleic acid-induced ALI results in the activation of MAPK signaling pathway and up-regulation of AQP-4 mRNA expression in the ATII cells of rats.

摘要

目的

探讨油酸诱导的大鼠早期急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)中Ⅱ型肺泡上皮细胞(AT-II)水通道蛋白4(AQP4)与丝裂原活化蛋白激酶(MAPK)信号通路之间的关系。

方法

本研究使用三组大鼠,即正常对照组、ALI组和U0126治疗组。后两组经油酸诱导ALI后,治疗组大鼠以10 μl剂量接受100 μmol/L U0126治疗,正常对照组和ALI组给予二甲基亚砜(DMSO)。治疗后测量动脉血气和血管外肺水(EVLW)含量,并显微镜下观察肺组织病理变化。从肺组织中分离ATII细胞,并用单宁酸染色和碱性磷酸酶(APK)染色进行鉴定。采用逆转录聚合酶链反应(RT-PCR)检测细胞中AQP-4 mRNA的表达。

结果

血气分析、苏木精-伊红(HE)染色和EVLW含量测量显示,ALI组肺组织损伤比正常对照组更严重,但治疗组和ALI组严重程度相当。RT-PCR显示,ALI组AQP-4 mRNA表达较正常对照组显著增加,U0126治疗使U0126治疗组AQP-4 mRNA表达明显降低。

结论

油酸诱导的ALI导致大鼠ATII细胞中MAPK信号通路激活及AQP-4 mRNA表达上调。

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