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| The protective effect and ameliorating cell apoptosis of Ulinastatin on lung tissue in septic rats |
| Li Yong-ning, Wang Lei, Chen Jun-jie, Li Xue-jiao, Wang Li-feng, Kang Jian |
| Department of Emergency, the First Affiliated Hospital of Medical University, Dalian 116011, China |
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Abstract Objective To investigate the protective role of Ulinastatin on lungs of rats with sepsis and its anti-apoptosis mechanism. Methods 30 male SD rats were randomly divided into three groups: the Sham group simply underwent open-close surgery; both the sepsis group and UTI group underwent cecal ligation and puncture (CLP); in UTI group, Ulinastatin 200,000U /kg was given 1 h prior to modeling, and was repeatedly given at 24 h post-treatment; the sepsis group received injection of normal saline. Caudal venous blood was collected at 6, 12, 24, 36, 48 h post-treatment to determine the mass concentrations of TNF-α, IL-6, and IL-10; lung specimens were retained at 48 h post-treatment to detect the expression of Bax/Bcl-2 and TUNEL by HE staining and IHC, and the expression of caspase-3 by Western-blot; ultrastructural changes in lung tissues were observed under transmission electron microscope (TEM). Results In UTI group, expression of the inflammatory cytokines TNF-α and IL-6 was higher than that in Sham group and lower than that in sepsis group(P<0.05); and the expression of the anti-inflammatory cytokine IL-10 was higher than that in sepsis group and lower than that in Sham group (P<0.05). HE staining revealed alveolar edema, congestion and inflammatory cell infiltration in sepsis group, which were significantly alleviated in UTI group; in sepsis group, expression of the apoptotic protein Bax was higher than that in UTI group, while expression of the anti-apoptotic protein Bcl-2 was lower than that in UTI group; the alveolar epithelial cell apoptosis rate detected by TUNEL was significantly lower in UTI group than in sepsis group (P<0.05); alveolar wall and capillary basement membrane swelling, reduced alveolar space, massive inflammatory exudation in alveolar space, and mitochondrial cavitation in type Ⅱ penumonocytes were observed under TEM, which were significantly alleviated in UTI group; the expression of caspase-3 protein detected by Western-blot was higher in Sham group than in sepsis group. Conclusion In rats with sepsis, Ulinastatin inhibits release of the pro-inflammatory mediators in serum, suppresses apoptosis of vascular endothelial cells and alveolar epithelial cells, and reduces caspase-3 expression, suggesting its protective role in acute lung injury in rats with sepsis.
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