丹参多酚酸盐对急性肺损伤防治作用的实验研究

An experimental research on salvianolate for prevention and treatment of acute lung injury in rats

目的 探讨丹参多酚酸盐对急性肺损伤（ALI）的防治作用.方法 32只成年大鼠按随机数字表法分为对照组、ALI组、糖皮质激素组、丹参多酚酸盐组,每组8只.采用间隔12 h连续2次向气管内注入内毒素脂多糖（LPS）1 ml/kg制备大鼠ALI模型,对照组经气管注入等量生理盐水.糖皮质激素组、丹参多酚酸盐组分别于制模后6、12、18、24 h给予糖皮质激素及丹参多酚酸盐各50 mg/kg.于给药后即刻（0）、12、18、24 h取颈动脉血,测定动脉血氧分压（PaO2）、白细胞计数（WBC）;于24 h测定肺动脉压（PAP）并取静脉血,采用酶联免疫吸附法（ELISA）测定血清肿瘤坏死因子-α（TNF-α）及白细胞介素-1（IL-1）含量;取肺组织测定肺湿/干重（W/D）比值.结果 ALI组各时间点PaO2均较对照组下降,WBC均较对照组升高（均P〈0.05）;而糖皮质激素组和丹参多酚酸盐组PaO2和WBC均较ALI组明显改善（均P〈0.05）.与对照组比较,ALI组PAP（mm Hg,1 mm Hg=0.133 kPa）、TNF-α（ng/L）、IL-1（ng/L）、肺W/D比值均显著增加（PAP：23.31±2.26比16.54±0.75;TNF-α：139.4±23.8比28.1±2.4;IL-1：383.5±70.1比93.1±31.2;肺W/D比值：8.9±1.7比4.8±0.6,均P〈0.05）;与ALI组比较,糖皮质激素组、丹参多酚酸盐组PAP、TNF-α、IL-1及肺W/D比值均明显降低[糖皮质激素组：PAP 19.55±1.50,TNF-α 56.6±2.7,IL-1 243.1±71.3,肺W/D比值 6.4±1.1;丹参多酚酸盐组：PAP 18.80±2.26,TNF-α 50.2±2.5,IL-1 231.4±74.3,肺W/D比值6.3±1.2,均P〈0.05],糖皮质激素组和丹参多酚酸盐组间各指标比较差异无统计学意义（均P＞0.05）.结论 丹参多酚酸盐可通过抗炎、调节免疫等方式对ALI起到预防和治疗的作用.

Objective To investigate the preventive and therapeutic effect of salvianolate in rats with acute lung injury （ALI）. Methods According to the random digits table, 32 adult rats were divided into four groups （n ： 8 in each group）： control group, ALI group, glucocorticoid group and salvianolate group. Intratracheal injection of lipopolysaccharide 1 ml/kg twice in series with an interval of 12 hours for establishing the model of ALI rats, equal amount of normal saline was intratracheally injected to the control group. 50 ml/kg corticosteroids and salvianolate were injected in glucocorticoid group and salvianolate group respectively 6, 12, 18, 24 hours after the establishment of the model. The arterial blood was collected from carotid artery at 0, 12, 18, 24 hours after drug injection, and the arterial partial pressure of oxygen （PaO2）, white blood cell （WBC） were tested. The pulmonary arterial pressure （PAP） was monitored at 24 hours, and the venous blood was taken. The tumor necrosis factor-α（TNF-α） and interleukin-1 （IL-1） were tested by enzyme linked immunosorbent assay （ELISA）, and the ratio of lung wet/dry weight （W/D） was calculated. Results Compared with control group, the PaO2 in all time points of ALI group was all reduced, while the WBC was elevated （all P〈0.05）. The PaO2 and WBC were improved in glucocorticoid group and salvianolate group （all P〈0. 05）. Compared with control group, the PAP （mm Hg, 1 mm Hg=0. 133 kPa）, TNF-α（ng/L）, IL-1 （ng/L）, W/D ratio of lung were all raised in ALI group （PAP： 23.31±2.20 vs. 16.5±0. 75; TNF-α： 139.4±23.8 vs. 28.1±2.4; IL-1： 383.5±70.1 vs. 93.1±31.2;W/D ratio： 8.9±1.7 vs. 4.8±0. 6, all P〈0.05）. Compared with ALI group, the PAP, TNF-α, IL-1, W/D ratio were all decreased in glucocorticoid group and salvianolate group （PAP： 19.55±1.50, TNF-a： 56.6±2.7, IL-1 ： 243.1 ± 71.3, W/D ratio： 6.4±1.1 in glucocorticoid group; PAP： 18.80±2.26, TNF-α： 50. 2±2.5, IL-1： 231.4±74.3, W/D ratio： 6.3 ± 1.2 in salvianolate group, all P〈0.05）, but still higher than those in the control group, the comparison of above mentioned indexes between glucocorticoid group and salvianolate being of no statistical significance （all P 〈 0.05）. Conclusion Salvianolate has preventive and therapeutic effect on ALI by anti-inflammatory and immune regulation.