肝素对急性肺损伤治疗保护作用的实验研究

THERAPEUTIC AND PROTECTIVE EFFECTS OF HEPARIN ON ACUTE LUNG INJURY

①目的 探讨肝素对急性肺损伤 (ALI)的治疗保护作用。②方法 选取Wistar大鼠 6 0只 ,随机分为生理盐水对照组 (A组 )、内毒素 (LPS)注射组 (B组 )、大剂量肝素治疗组 (C组 )、中等剂量肝素治疗组 (D组 )和小剂量肝素治疗组 (E组 )。除A、B组向大鼠腹腔内分别注射生理盐水和内毒素外 ,其他组向大鼠腹腔内注射LPS后 4h ,再注射不同剂量肝素 ,12h后处死大鼠。每组随机选取 7只大鼠取肺组织测肺含水量并进行病理检查。各组余5只大鼠断颈后取外周血并行支气管肺泡灌洗 ,应用ELISA法检测血及支气管肺泡灌洗液 (BALF)中的肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、白细胞介素 8(IL 8)浓度 ;取其沉淀物 ,经Wright染色 ,计数 10 0个细胞中多形核白细胞 (PMN)所占百分比并计数白细胞。③结果 B、C、D、E组TNF α、IL 1β、IL 8浓度明显高于A组 (F=7.71～ 2 1.2 0 ,q =5 .2 2～ 7.80 ,P <0 .0 1) ;其中灌洗液中的浓度高于血浆中的浓度 (t=4 .32～ 10 .0 5 ,P <0 .0 5 ) ;C、D、E组浓度较B组明显下降 (q =3.6 4～ 5 .70 ,P <0 .0 5 )。B、C、D、E组BALF中WBC计数及PMN所占百分比与A组比较 ,差异均有显著性 (F =5 8.0 0、32 .34,q =6 .76～ 2 0 .83,P <0 .0 5 ) ;C、D、E组与B组比较差异均有显著性 (q

Objective To investigate the therapeutic and protective effects of heparin on acute lung injury(ALI). Methods Sixty Wistar rats were randomly divided into five groups, normal control (A); lipopolysaccharide(LPS) (B); LPS and large-dose heparin (C); LPS and medium-dose heparin (D); LPS and minimal-dose heparin (E). Group A were made by injecting NS into the rat abdoments. The rat models of ALI were made by injecting LPS into the rat abdomens. Four hours later, the rats in Groups C, D, and E were injected with heparin of 1500, 250, and 75u/kg, respectively. All the rats were killed 12 hours later. Seven rats were randomly taken from each group for determination of the water contents in their lung tissues, and sent for histology. Contents of tumor necrosis factor-α(TNF-α), interleakin-1β(IL-1β) and interleakin-8 (IL-8) in plasma and bronchoalveolar lavagefluid (BALF) in the remaining five rats in each group were measured by ELISA. The WBC and its percentage of polymorphonuclear leukocyte (PMN) in BALF and plasma were counted. Results Thelevels of plasma and BALF TNF-α, IL-1β and IL-8 in Groups B, C, D and E were higher than those in group A ( F=7.71-21.10, q=5.22-7.80, P<0.01). The BALF levels were higher than those in the plasma (t=4.32-10.05, P<0.05). The levels in Groups C, D and E were markedly lower than those in Group B (q=3.64-5.70, P<0.05). BALF WBC counts and PMN percentages in Groups B, C, D, and E differed significantly from those in Group A (F=58.00, 32.34; q=6.67-20.83; P<0.05), and those in Groups C, D, and E differed significantly from those in Group B (q=6.31-14.07, P<0.01). Conclusion Heparin has therapeutic and protective effects on acute lung injury.