雷公藤内酯醇可改善脂多糖诱导的大鼠急性肺损伤。
Triptolide ameliorates lipopolysaccharide-induced acute lung injury in rats.
机构信息
Department of Anesthesiology, First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, Jiangsu 215006, China.
出版信息
Eur J Med Res. 2013 Dec 17;18(1):58. doi: 10.1186/2047-783X-18-58.
BACKGROUND
Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of triptolide on lipopolysaccharide (LPS)-induced ALI in rats were investigated.
METHODS
Sixty-five male Sprague Dawley rats(approved by ethics committee of the First Affiliated Hospital of Soochow University) were randomly divided into five groups. The control group was injected with 2.5 mL saline/kg body weight via the tail vein and intraperitoneally with 1% dimethyl sulfoxide (DMSO) (n = 5). The L group was administered with 0.2% LPS dissolved in saline (5 mg/kg) to induce ALI via the tail vein (n = 15). The TP1, TP2, and TP3 groups were treated as rats in the L group and then intraperitoneally injected with 25, 50, and 100 μg triptolide/kg body weight, respectively (15 rats per group). Blood samples from the left heart artery were taken for blood gas analysis at 1 hour before injection and at 1, 3, 6, and 12 hours after saline and DMSO administration in the control group, LPS injection in the L group, and triptolide injection in the TP1, TP2, and TP3 groups. Lung wet-to-dry weight (W/D) ratio, diffuse alveolar damage (DAD) score, TNF-α levels, and mRNA and protein expression of toll-like receptor 4 (TLR4) were analyzed.
RESULTS
Compared with the control group, the arterial partial pressure of oxygen (PaO2) declined (P <0.05), the W/D ratio and DAD score increased (P <0.05), and TNF-α levels in serum and bronchoalveolar lavage fluid (BALF) and mRNA and protein expression of TLR4 were significantly increased in the L group (P <0.05). Compared with the L group, PaO2 significantly increased in the TP2 and TP3 groups (P <0.05), while the W/D ratio and DAD score were significantly decreased in the TP2 and TP3 groups (P <0.05). TNF-α levels and mRNA and protein expression of TLR4 were significantly decreased in the TP2 and TP3 groups compared with the L group (P <0.05).
CONCLUSIONS
Triptolide can ameliorate LPS-induced ALI by reducing the release of the inflammatory mediator TNF-α and inhibiting TLR4 expression.
背景
急性肺损伤（ALI）是一种死亡率较高的严重临床综合征。本研究旨在探讨雷公藤内酯醇对脂多糖（LPS）诱导的大鼠 ALI 的影响。
方法
65 只雄性 Sprague Dawley 大鼠（苏州大学第一附属医院伦理委员会批准）随机分为五组。对照组经尾静脉注射 2.5 mL 生理盐水/kg 体重，腹腔注射 1%二甲亚砜（DMSO）（n=5）。L 组通过尾静脉注射 0.2%LPS 生理盐水（5mg/kg）诱导 ALI（n=15）。TP1、TP2 和 TP3 组作为 L 组大鼠，然后分别腹腔注射 25、50 和 100μg 雷公藤内酯醇/kg 体重（每组 15 只）。对照组在注射前 1 小时和注射后 1、3、6 和 12 小时从左心动脉采血进行血气分析，L 组注射 LPS，TP1、TP2 和 TP3 组注射雷公藤内酯醇。分析肺湿重/干重（W/D）比、弥漫性肺泡损伤（DAD）评分、TNF-α 水平以及 Toll 样受体 4（TLR4）的 mRNA 和蛋白表达。
结果
与对照组相比，动脉部分氧分压（PaO2）下降（P<0.05），W/D 比和 DAD 评分增加（P<0.05），血清和支气管肺泡灌洗液（BALF）中 TNF-α 水平以及 TLR4 的 mRNA 和蛋白表达明显增加（P<0.05）。与 L 组相比，TP2 和 TP3 组 PaO2 明显升高（P<0.05），TP2 和 TP3 组 W/D 比和 DAD 评分明显降低（P<0.05）。与 L 组相比，TP2 和 TP3 组 TNF-α 水平以及 TLR4 的 mRNA 和蛋白表达明显降低（P<0.05）。
结论
雷公藤内酯醇通过减少炎症介质 TNF-α 的释放并抑制 TLR4 表达，可改善 LPS 诱导的 ALI。
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