[The expression levels of endothelin-1 and nuclear factor-kappaB in the lung tissue of acute pulmonary embolism and the effects of thrombolysis and dexamethasone].
OBJECTIVE
To study the expression levels of endothelin-1(ET-1) and nuclear factor-kappaB (NF-kappaB) in lung vascular endothelium, bronchial and alveolar epithelia in acute pulmonary thromboembolism (APTE), and to explore the effects of thrombolytic (urokinase, UK) or ant-inflammatory therapy (dexamethasone, Dex) on their expressions.


METHODS
Forty rabbits were randomly divided into a control (C) group, a pulmonary thromboembolism (PTE) model group, an UK therapy group, a Dex therapy group, and an UK + Dex therapy group, with 8 rabbits each. The PTE model was established by intravenous injection of autologous blood clots. The pathological changes of the lung were examined with light microscope. By using immunohistochemistry, the expression levels of ET-1 and NF-kappaB P65 in lung vascular endothelium, bronchial and alveolar epithelia were examined.


RESULTS
Histopathological study showed that lung injury was evident in the PTE, UK and Dex groups, but was mild in the UK + Dex group. In the PTE group, the expression levels of ET-1 in lung vascular endothelium, bronchial and alveolar epithelia were 0.331 +/- 0.036, 0.229 +/- 0.014 and 0.191 +/- 0.046, respectively, while the expression levels of NF-kappaB P65 were 0.245 +/- 0.036, 0.190 +/- 0.040 and 0.204 +/- 0.054, respectively. Their levels were significantly higher as compared to those of the control group and the UK + Dex group (all P < 0. 01). In the UK group, the ET-1 expression in lung vascular endothelium, bronchial and alveolar epithelia were 0.204 +/- 0.020, 0.163 +/- 0.017 and 0.137 +/- 0.013 respectively, significantly lower as compared to the PTE group (all P < 0. 05). In the Dex group, the NF-kappaB P65 expression was 0.175 +/- 0.024, 0.104 +/- 0.022 and 0.144 +/- 0.022 respectively, the difference being significant as compared with the PTE group (all P < 0. 05). In the UK + Dex group, the ET-1 expression was 0.186 +/- 0.033, 0.107 +/- 0.012 and 0.098 +/- 0.026 respectively, significantly different from the PTE group (all P < 0.05); the NF-kappaB P65 expression was 0.109 +/- 0.018, 0.062 +/- 0.023 and 0.093 +/- 0.019 respectively, significantly lower as compared with the PTE and the UK groups (all P < 0. 01).


CONCLUSIONS
After APTE, thrombolytic and anti-inflammatory treatment could decrease acute lung injury induced by ET-1 and NF-kappaB activation. Thus, anti-inflammatory therapy and the use of ET-1 inhibitor or receptor antagonist should be considered in APTE.
Zhang
Dou-xia
DX
Department of Respiratory Medicine, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhang
Ling
L
Bai
Ming
M
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D019332:Endothelin-1 / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits
D019332:Endothelin-1; D005343:Fibrinolytic Agents; D016328:NF-kappa B; D003907:Dexamethasone