Wang Q L, Shang X Y, Zhang S L, Ji J B, Cheng Y N, Meng Y J, Zhu Y J
Department of Pharmacology, College of Pharmacy, Shandong Medical University, Jinan, PR China.
Jpn J Pharmacol. 2000 Apr;82(4):326-30. doi: 10.1254/jjp.82.326.
Low molecular weigh, heparin (LMWH) possesses multiple nonanticoagulant properties. In the present study, we observed its anti-airway allergic inflammatory effects by bronchoalveolar lavage in guinea pigs. Guinea pigs were sensitized by repeatedly inhaling aerosolized ovalbumin. LMWH (400 u/l, 800 u/l), dexamethasone (1.2 mg/1) or vehicle (normal saline) was inhaled for 7 days. Then the animals were sacrificed under anesthesia and then lavaged with ice-cold Hank's buffer immediately; bronchoalveolar lavage fluid (BALF) was prepared 24 h after the animals were challenged by antigen exposure. The effects of LMWH on total cell counts, absolute eosinophil counts and cell catalogues in BALF were studied; effects on the activity of eosinophil peroxidase (EPO) and the contents of histamine and eosinophil cationic protein (ECP) in BALF supernatant were detected. Our results showed that compared with the vehicle group, LMWH at 400 u/l and 800 u/1 could significantly reduce total cell counts, absolute eosinophil counts and percentage of eosinophils in BALF (P<0.05 and P<0.01, respectively); LMWH at 800 u/l markedly inhibited the activity of EPO in BALF supernatant (P<0.05); LMWH at 400 u/l and 800 u/l remarkably reduced the content of histamine in BALF supernatant (P<0.05 and P<0.01, respectively), LMWH at 800 u/l decreased the content of ECP (P<0.05) significantly. It suggested that LMWH exerted anti-airway allergic inflammatory action by inhibiting infiltration of inflammatory cells and reducing release of inflammatory mediators, as well as antagonizing their activities, and that LMWH could be developed as a potential anti-bronchial asthmatic drug.
低分子量肝素(LMWH)具有多种非抗凝特性。在本研究中,我们通过豚鼠支气管肺泡灌洗观察了其抗气道过敏性炎症作用。豚鼠通过反复吸入雾化卵清蛋白致敏。吸入LMWH(400 U/l、800 U/l)、地塞米松(1.2 mg/1)或赋形剂(生理盐水)7天。然后在麻醉下处死动物,立即用冰冷的汉克缓冲液灌洗;在动物经抗原激发24小时后制备支气管肺泡灌洗液(BALF)。研究了LMWH对BALF中总细胞计数、嗜酸性粒细胞绝对计数和细胞分类的影响;检测了对BALF上清液中嗜酸性粒细胞过氧化物酶(EPO)活性以及组胺和嗜酸性粒细胞阳离子蛋白(ECP)含量的影响。我们的结果表明,与赋形剂组相比,400 U/l和800 U/1的LMWH可显著降低BALF中的总细胞计数、嗜酸性粒细胞绝对计数和嗜酸性粒细胞百分比(分别为P<0.05和P<0.01);800 U/l的LMWH显著抑制BALF上清液中EPO的活性(P<0.05);400 U/l和800 U/l的LMWH显著降低BALF上清液中组胺的含量(分别为P<0.05和P<0.01),800 U/l的LMWH显著降低ECP的含量(P<0.05)。这表明LMWH通过抑制炎症细胞浸润、减少炎症介质释放以及拮抗其活性发挥抗气道过敏性炎症作用,并且LMWH可开发成为一种潜在的抗支气管哮喘药物。