赤芍对大鼠内毒素急性肺损伤丝裂原活化蛋白激酶p38/NF-κB/iNOS的影响

Effect of radix paeoniae rubra on expressions of p38MAPK,NF-κB and iNOS in a rat model of li-popolysaccharide-induced acute lung injury

目的 观察赤芍对大鼠内毒素性急性肺损伤（acute lung injury,ALI）丝裂原活化蛋白激酶p38（p38MAPK）/NF-κB/诱导型-氧化氮合酶（iNOS）信号通路的影响,探讨其防治作用的分子机制. 方法采用大鼠内毒素ALI模型,40只Wistar大鼠完全随机分为假手术对照组（A组）、内毒素组（B组）、赤芍治疗组（C组）、赤芍预防组（D组）和SB203580组（E组）,每组8只大鼠.观察赤芍对肺组织中p38MAPK、NF-κB和iNOS表达的影响,肺泡灌洗液中性粒细胞比和蛋白含量、肺组织丙二醛（MDA）含量及血清NO含量的变化,于LPS滴注后6 h行血气分析,并进行病理学观察. 结果与A组比较,B、C、D和E组p38MAPK、NF-κB和iNOS表达显著增强,肺泡灌洗液中性粒细胞比和蛋白含量、肺组织MDA含量和血清NO含量显著增加,PaO2和HCO3-明显降低（P〈0.05或0.01）;与B组比较,C、D组和E组p38MAPK、NF-κB和iNOS表达明显降低（P〈0.05）;肺泡灌洗液中性粒细胞比和蛋白含量、肺组织MDA显著减少,PaO2和HCO3-明显升高（P〈0.05或〈0.01）.病理学显示C、D组和E组肺组织损伤程度较B组明显减轻;c、D、E组之间各项指标差异无统计学意义.结论 赤芍对内毒素性ALI的防治作用可能与抑制p38MAPK/NF-κB/iNOS信号通路密切相关.

Objective To investigate the effect of radix paeoniae rubra （RPR） on expressions of p38MAPK, NF-κB and iNOS in ltpopolysaccharide （LPS）-induced acute lung injury （ALI） and explore its protective mechanism. Methods Forty Wistar rats with ALI were divided randomly into five groups： saline control group （Group A） , LPS group （Group B）, RPR for treatment group （Group C）, RPR for prevention group （Group D） and SB203580 group （Group E）. The effects of RPR on protein content and the ratio of neutrophiles in bronchoalveolar lavage fluid （BALF）, contents of malondidehyde （MDA） and serum NO in lung tissue were observed. Arterial blood was collected for blood gas analysis. Expressions of p38MAPK, NF-κB and iNOS in rat lung tissues were detected. Results Compared with Group A, expressions of p38MAPK, NF-κB and iNOS were significantly increased （P 〈0.01 orP〈 0.05） , the protein content and the ratio of neutrophiles in BALF, contents of MDA and serum NO were significantly higher （P〈0.01 or P〈0.05） in Groups B, C, D and E. There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in Groups B, C, D and E （P〈0.01 or P〈0.05）. Compared with Group B, the expressions of p38MAPK, NF-κB and iNOS were significantly lower, and the protein content and the ratio of neutrophiles in BALF, contents of MDA and serum NO were significantly decreased, while the levels of arterial bicarbonate and partial pressure of oxygen were significantly higher in Groups C, D and E （P〈0.05 or P〈0.01）. Compared with Group B, the lunginjury of Groups C, D and E was significantly alleviated, while there was no statistical difference among Groups C, D and E in the indices of lung injury. Conclusion Protective effect of RPR on LPS-induced ALI is closely related to the inhibited expressions of p38MAPK, NF-κB and iNOS.