血必净与西维来司他钠对ALI/ARDS大鼠肺保护作用的比较研究

Comparative study of the protective effect of Xuebijing injection and Sivelestat sodium on acute lung injury/acute respiratory distress syndrome rats

目的比较血必净注射液(血必净)与西维来司他钠注射液(西维来司他钠)对急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)大鼠的保护作用。方法将71只雄性SD大鼠随机分为空白对照组(8只)、ALI/ARDS模型组(21只)、血必净组(21只)和西维来司他钠组(21只)共4组。采用经大鼠尾静脉注射25 mg/kg脂多糖(LPS)建立ALI/ARDS模型,空白对照组大鼠给予生理盐水;之后血必净组每日2次经尾静脉给予8 mL/kg血必净注射液,西维来司他钠组每日3次腹腔注射100 mg/kg西维来司他钠,空白对照组和ALI/ARDS模型组每日2次腹腔注射等量生理盐水,各组均连续给药5 d。实验期间观察大鼠一般状态,记录体质量和存活情况,实验终点时收集大鼠肺泡灌洗液检测炎症细胞和炎症因子,并观察大鼠肺组织病理学改变。结果与ALI/ARDS模型组相比,血必净组和西维来司他钠组肺泡灌洗液中白细胞计数(WBC)和中性粒细胞比例(NEU%)均明显降低〔WBC(×109/L):55.86±6.68、49.96±6.76比73.13±7.35,NEU%:0.459±0.077、0.315±0.047比0.709±0.067,均P<0.05〕,淋巴细胞比例(LYM%)明显升高(0.412±0.067、0.517±0.051比0.232±0.057,均P<0.05),白细胞介素-6(IL-6)水平均有所降低(ng/L:295.2±39.7、281.9±33.1比469.6±77.0);但血必净组与西维来司他钠组比较差异均无统计学意义(均P>0.05)。血必净组实验终点时的存活率高于西维来司他钠组和ALI/ARDS模型组〔52.4%(11/21)比28.6%(6/21)、14.3%(3/21)〕,西维来司他钠组高于ALI/ARDS模型组,但3组间差异无统计学意义(P>0.05);实验终点时血必净组体质量及其增长率均高于西维来司他钠组体质量(g):217.1±6.4比207.1±7.0,体质量增长率:(-0.9±2.8)%比(-4.3±3.5)%〕,但差异无统计学意义(均P>0.05)。肺组织病理学观察显示,光镜下可见ALI/ARDS模型组大鼠肺泡腔内大量炎症物质渗出,其中充满炎症细胞,局部可见肺泡上皮细胞损伤,肺泡结构破坏;血必净组大鼠上述情况均有所改善;西维来司他钠组的肺组织病理学改变与血必净组基本相同。结论血必净注射液可通过抑制炎症反应,减轻ALI/ARDS导致的肺组织损伤和全身性损害,提高大鼠存活率,其保护作用与西维来司他钠注射液基本一致。

Objective To compare the protective effect of Xuebijing injection versus Sivelestat sodium on acute lung injury/acute respiratory distress syndrome(ALI/ARDS)rats.Methods A total of 71 male Sprague-Dawley(SD)rats were randomly divided into the blank control group(n=8),ALI/ARDS model group(n=21),Xuebijing injection group(n=21)and Sivelestat sodium group(n=21).Rats in the blank control group were injected with normal saline while the other three groups were intravenously injected 25 mg/kg lipopolysaccharide(LPS)via the tail vein to establish ALI/ARDS model.After induction of ALI/ARDS model,the blank control group and ALI/ARDS model group were given intraperitoneal injection of an equal volume of normal saline twice a day.Rats in the Xuebijing injection group were given tail vein injection of 8 mL/kg Xuebijing injection twice a day,and those in the Sivelestat sodium group were given intraperitoneal injection of 100 mg/kg Sivelestat sodium three times a day.All rats were administered continuously for five days.During the experiment,the general status of rats was observed,and the weight and survival were recorded.At the end of the experiment,bronchoalveolar lavage fluid(BALF)of rats was collected for the detection of inflammatory cells and inflammatory factors.Histopathological changes of rats lung tissue were observed.Results Compared with the ALI/ARDS model group,the Xuebijing injection group and Sivelestat sodium group had significantly decreased white blood cell(WBC)count and percent of neutrophil(NEU%)[WBC(×109/L):55.86±6.68,49.96±6.76 vs.73.13±7.35,NEU%:0.459±0.077,0.315±0.047 vs.0.709±0.067,all P<0.05],significantly increased percent of lymphocytes(LYM%:0.412±0.067,0.517±0.051 vs.0.232±0.057,both P<0.05),and reduced interleukin-6(IL-6)level(ng/L:295.2±39.7,281.9±33.1 vs.469.6±77.0)in BALF.However,there were no significant differences in these parameters between the Xuebijing injection group and Sivelestat sodium injection group(all P>0.05).Survival rate at the end of experiment was higher in the Xuebijing group than that in the Sivelestat sodium injection group and ALI/ARDS model group[52.4%(11/21)vs.28.6%(6/21),14.3%(3/21)],and survival rate at the end of experiment was higher in the Sivelestat sodium injection group than that in the ALI/ARDS model group,but the differences were not statistically significant(P>0.05).In addition,weight and weight growth rate in the Xuebijing injection group were higher than the Sivelestat sodium group at the end of the experiment[weight(g):217.1±6.4 vs.207.1±7.0,weight growth rate:(-0.9±2.8)%vs.(-4.3±3.5)%],there were no significant difference between the two groups(both P>0.05).Lung histopathology in the ALI/ARDS model group revealed high level of inflammatory exudate and inflammatory cells infiltrated in the alveoli of rats,along with damage of local alveolar epithelial cell and alveolar structure.However,these histological changes were improved in the Xuebijing injection group and in the Sivelestat sodium group.Conclusions Xuebijing injection can alleviate ALI/ARDS-induced lung injury and systemic damage and improve the survival of rats by inhibiting inflammation.The protective effect of Xuebijing injection is essentially consistent with that of Sivelestat sodium.