Effect of Losartan on the Expression of TNF-α and MPO in the Lung of Mechanically Ventilated Rats
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    Abstract:

    ObjectiveTo explore the effect of an AT1 inhibitor losartan on the expression of TNF-α and myeloperoxidase (MPO) in the lung of mechanically ventilated rats, and further study the protective effect of losartan on ventilator induced lung injury. MethodsTwenty-four healthy male Wister rats were randomly divided into three groups:control group, ventilator induced lung injury (VILI) group and losartan group. ELISA in situ was used to determine the blood content of angiotensin II (Ang Ⅱ) in the lung tissue, immunohistochemical staining was employed to detect the expression level of TNF-α protein, and colorimetry was applied to measure the activity of myeloperoxidase (MPO) in the homogenate of lung tissue. ResultsThe Ang Ⅱ concentration and expression level of TNF-α protein in the lung tissue, and MPO activity in the homogenate of lung tissue of the VILI group were significantly higher than those in the control group (P<0.01). There was no significant difference between the Ang Ⅱ concentration and MPO activity in the losartan group and VILI group (P>0.05). However, the expression level of TNF-α protein, MPO activity and wet/dry lung weight (W/D) ratio were significantly decreased in the losartan group in comparison with that of the VILI group (P<0.01), and the lung injury was apparently less serious than that in the VILI group. ConclusionsAng Ⅱ regulates the expression of TNF-α in the lung tissue and play an important role in the pathogenesis of ventilator-induced lung injury. Losartan may block the binding of Ang Ⅱ and AT1 receptor, down-regulate the expression of TNF-α protein and decrease the MPO activity of lung tissue homogenate, and may have preventive and therapeutic effect on ventilator-induced lung injury to some degree.

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