Inhibition of matrix metalloproteinase-9 with low-dose doxycycline reduces acute lung injury induced by cardiopulmonary bypass

低剂量强力霉素抑制基质金属蛋白酶-9可减轻体外循环引起的急性肺损伤

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作者:Chengxin Zhang, Wenhui Gong, Haiyuan Liu, Zhixiang Guo, Shenglin Ge

Conclusion

The results suggested that doxycycline protected the acute lung injury induced by CPB through reducing the concentration of MMP-9 and degradation of the cell membrane, pulmonary neutrophil infiltration and pulmonary edema.

Methods

A total of 30 healthy mongrel dogs were randomly divided into three groups: Group A (CPB control group, no treatment of doxycycline), Group B (low-dose group, treated with doxycycline at 30 mg/kg) and Group C (high-dose group, doxycycline at 60 mg/kg). The alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were calculated, the concentration of MMP-9 in plasma was measured by ELISA. The expression levels of MMP-9 was determined by RT-PCR. The lung W/D index was calculated. The myeloperoxidase (MPO) activity of bronchoalveolar lavage fluid (BALF) was measured by colorimetry. The total protein of BALF was measured by Coomassie brilliant blue G-250. The white blood count (WBC) in the sediment of BALF was counted.

Objective

This study aims to demonstrate the protective effect of doxycycline, an exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), in the acute lung injury induced by cardiopulmonary bypass (CPB).

Results

A-aDO2, RI, total protein, and MPO activity of BALF, WBC count in BALF sediment and W/D index in group B were significantly lower than that of control group (P < 0.05). The concentration of MMP-9 in group C decreased significantly (P < 0.05). There were no significant differences in gene expression among the three groups.

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