低分子肝素与尿激酶对兔急性实验性肺栓塞MCP-1的影响

[The effect of low molecular heparin and urokinase on MCP-1 of acute experimental pulmonary embolism in rabbits].

作者信息

Yu Hongzhi, Wu Qi, Wu Junping, Sun Xin, Du Zhongzhen, Li Li, Wu Qian

机构信息

Department of Respiratory Medicine, Tianjin Haihe Hospital, Tianjin 300350, China.

Department of Respiratory Medicine, General Hospital of Tianjin Medical University, Tianjin 300052, China. Email:

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2014 Jun;37(6):437-41.

PMID:25200044

Abstract

OBJECTIVE

To evaluate effect the of thrombolytic (urokinase, UK) and anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary injury of rabbits with acute pulmonary embolism (PE) by assaying monocyte chemoattractant protein-1 (MCP-1).

METHODS

Rabbit models with PE were established by transfusing autologous blood clots on 60 healthy male Japanese white rabbits. Experimental PE rabbits were randomly divided into 3 groups:normal saline (NS) group (n = 18) , LMWH group (n = 18) and UK group (n = 18), and other 18 rabbits underwent sham operations as SHAM group (n = 18). Each group was divided into 3 subgroups based on 2 days (day 2), 4 days (day 4), and 14 days (day 14) after therapies. Arterial blood gas analysis was measured. MCP-1 levels in lung tissue and blood were assayed with ELISA at various times (day 2, day 4 and day 14 ). Fixed sections were stained with trichrome for intimal hyperplasia determination.

RESULTS

The overall rate of success for making PE rabbit models was 90% (54/60), which was not affected by treatment. Compared with NS group, P(A-a)O2 significantly decreased in UK group. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in LMWH group on day 4 [(33 ± 9) ng/L vs (48 ± 5) ng/L, P < 0.05] and day 14 [(30 ± 11) ng/L vs (41 ± 4) ng/L, P < 0.05]; MCP-1 levels in serum on day 14 also significantly decreased in LMWH group [(36 ± 10) ng/L vs (51 ± 5) ng/L, P < 0.05]. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in UK group on day 2 and 4 [Day 2: (34 ± 8) ng/L vs (50 ± 4) ng/L, P < 0.05; Day 4: (29 ± 7) ng/L vs (48 ± 5) ng/L, P < 0.05]; MCP-1 levels in serum on day 2 and day 4 also significantly decreased in UK group [Day 2: (44 ± 3) ng/L vs (48 ± 3) ng/L, P < 0.05; Day 4: (44 ± 4) ng/L vs (53 ± 1)ng/L, P < 0.05].

CONCLUSIONS

UK treatment may rapidly improve V/Q ratio and decrease MCP-1 levels in lung tissue or serum, but it can not inhibit persistent inflammation. LMWH can decrease MCP-1 levels in lung tissue or serum, and inhibit persistent inflammation and late intimal hyperplasia.

摘要

目的

通过检测单核细胞趋化蛋白-1（MCP-1），评估溶栓剂（尿激酶，UK）和抗凝剂（低分子肝素，LMWH）对急性肺栓塞（PE）家兔肺损伤的影响。

方法

对60只健康雄性日本大耳白兔输注自体血凝块建立PE兔模型。将实验性PE兔随机分为3组：生理盐水（NS）组（n = 18）、LMWH组（n = 18）和UK组（n = 18），另外18只兔接受假手术作为假手术组（SHAM组，n = 18）。每组根据治疗后2天（第2天）、4天（第4天）和14天（第14天）分为3个亚组。进行动脉血气分析。在不同时间点（第2天、第4天和第14天）用ELISA法检测肺组织和血液中的MCP-1水平。固定切片用三色染色法测定内膜增生情况。

结果

制作PE兔模型的总体成功率为90%（54/60），不受治疗影响。与NS组相比，UK组的P（A-a）O2显著降低。与NS组相比，LMWH组在第4天[（33±9）ng/L对（48±5）ng/L，P<0.05]和第14天[（30±11）ng/L对（41±4）ng/L，P<0.05]肺组织中的MCP-1水平显著降低；LMWH组在第14天血清中的MCP-1水平也显著降低[（36±10）ng/L对（51±5）ng/L，P<0.05]。与NS组相比，UK组在第2天和第4天肺组织中的MCP-1水平显著降低[第2天：（34±8）ng/L对（50±4）ng/L，P<0.05；第4天：（29±7）ng/L对（48±5）ng/L，P<0.05]；UK组在第2天和第4天血清中的MCP-1水平也显著降低[第2天：（44±3）ng/L对（48±3）ng/L，P<0.05；第4天：（44±4）ng/L对（53±1）ng/L，P<0.05]。