丹参酮IIA磺酸钠对脂多糖致小鼠急性肺损伤的预防与治疗作用及其机制  

The preventive and therapeutical effect of STS on ALI induced by LPS in mice

作　　者：许敏[1] 李志超[1] 董明清[1] 王晓斌[1] 刘曼玲[1] 董海莹[1] 黄玉芳[1] 栾丽丽[1] 

机构地区：[1]第四军医大学病理生理学教研室,陕西西安710032

出　　处：《中国药理学通报》2008年第4期477-481,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30770925,30400155)

摘　　要：目的观察丹参酮IIA磺酸钠(STS)对脂多糖(LPS)引起的小鼠急性肺损伤(ALI)的预防与治疗作用,并初步探讨其作用机制。方法昆明种小鼠随机分为生理盐水(NS)对照组、STS对照组、LPS组、STS+LPS组及LPS+STS组,腹腔注射LPS建立小鼠急性肺损伤模型。造模6h后观察肺组织形态学改变,测定左肺湿/干重比值(W/D)、肺/体重比值(L/B)、肺泡灌洗液(BALF)中蛋白含量及肺组织匀浆中髓过氧化物酶(MPO)活力,同时微量滴定法检测肺组织匀浆与BALF中磷脂酶A2(PLA2)的活性。结果形态学观察表明LPS组肺组织明显充血、水肿,并有大量炎性细胞浸润,而在STS+LPS组及LPS+STS组内毒素所致肺损伤明显减轻;W/D、L/B、BALF中蛋白含量与肺匀浆MPO活力LPS组较对照组明显升高(P<0·05),但STS+LPS组及LPS+STS组较LPS组明显减低(P<0·05)。LPS组小鼠肺匀浆与BALF中PLA2活性为[(49·2±4·3)U与(40·8±6·5)U],均高于正常对照组[(23·8±4·8)U与(27·2±6·9)U],而在STS+LPS组及LPS+STS组分别降为[(29·0±5·8)U,(30·0±5·8)U]与[(31·4±4·9)U,(31·0±3·8)U],与LPS组相比差异有统计学意义。结论STS能够对LPS导致的小鼠急性肺损伤起预防与治疗作用,这种保护作用可能与其通过抑制肺中PLA2活力作用有关。Aim To observe the role of sodium tanshinone sulphonate IIA （STS） in the prevention and treatment of LPS-induced acute lung injury （ALI） of mice, and further explore the underlying mechanism by which STS exerts protective effects on LPS-induced ALL Methods KM mice were randomly divided into five groups： saline control group, STS group, group, STS ＋ LPS group and LPS ＋ STS group ; the animal model of ALI was established by intraperitoneal administration of LPS（ 10 mg· kg^-1 ）. Six hours after establishing the animal model, the histological changes of lungs were observed, and the left lung wet-to-dry （W/D） and lung-to-body （L/B） weight ratios, protein content in bronchoalveolar lavage fluid （BALF） and myeloperoxidase （MPO） activity in lung homogenate were measured. Meanwhile, PLA2 activities in both lung homogenate and BALF were evaluated with microtiter method. Results Histological studied showed that there were congestion, edema and the sequestration of inflammatory cells in lung tissues in LPS group, but lung injury was significantly alleviated in STS ＋ LPS and LPS ＋ STS groups; the W/D, L/B, protein content in BALF and MPO activity in lung homogenate were highly increased in LPS group （P 〈 0. 05 ）, and both prevention and therapy of STS can in- hibit the increased parameters （ P 〈 0. 05 ）. The PLA2 activities in lung homogenate and BALF in LPS group were [ （49.2 ±4. 3 ） U and （40. 8 ± 6. 5 ） U ], which were higher than that in the control group [ （23.8 ±4. 8） U and （27.2± 6. 9） U ] ; the PLA2 activities in STS ＋ LPS and LPS ＋ STS groups were reduced to [（29.0±5.8）U, （30.0±5.8）U] and [（31.4 ± 4. 9 ） U, （31.0 ± 3.8 ） U ] respectively, which had significant difference compared with LPS group. Conclusion STS could play an important role in prevention and treatment of mice ALI induced by LPS, and the mechanism of protection was correlated with inhibition of lung PLA2 activity.

关 键 词：急性肺损伤 脂多糖 丹参酮 ⅡA磺酸钠 磷脂酶A2 

分 类 号：R-332[医药卫生] R284.1