| Objective: Sepsis is an uncontrolled systemic inflame- matory response syndrome. The present study shows that sepsis is the most common cause of acute lung injury (ALI). At the same time, the treatment for sepsis and the multiple organ dysfunction syndrome (MODS) is intractable with a high mortality rate, up to 70 %. Matrix metalloproteinases (MMPs) is a zinc-dependent proteolytic enzyme, and its main function is related to decompose extracellular matrix (ECM). Matrix met- alloproteinase-9 (MMP-9) is a key point of many diseases, and it is produced by inflammatory cells such as neutrophils, monocytes, macrophages and eosinophils. MMP-9 can decom- pose basement membrane after it is activated. This will result in the leak of WBC, and promote inflammation. Xuebijing inject- tion is a kind of extractive of Chinese herbal medicines. After a large number of longterm basic and clinical researches, it is an effective drug that can antagonize bacterial toxins, lower the endotoxin level, regulate the immune and inflammatory medium, improve microcirculation and protect endothelial cells. Some animal experiments, as well as some clinical trials, showed that Xuebijing injection was beneficial to the treatment for heavy patients with systemic inflammatory response or even sepsis. This research was conducted to investigate the serum level changes of MMP-9 and the pathological changes of lung tissue in rats with sepsis induced by CLP, and to study the protection mechanism of action of Xuebijing injection in lung.Method: In this study, the septic rat models were challenged by CLP. Thirty six male Sprague-Dawley (250-300g) rats were divided randomly into 3 groups: sham group (n=12), in which the rats'abdomen just be open and then closed, was treated with saline 4mL/kg through tail vein; NS group (n=12), treated with saline 4mL/kg through tail vein after CLP; X group (n=12), treated with Xuebijing injection 4mL/kg through tail vein after CLP. The rats with sepsis were induced by cecal ligation and puncture (CLP). After 6 hour, blood was catched from each rat via carotid artery, then serum MMP-9 was determined by the method of ELISA. In order to determine the lung wet/dry weight ratio, the right middle lung lobe tissue sample was taken after the rat was killed and excess fluid was blotted from specimens. Wet weight was measured immediately and dry weight was measured after drying specimens at 85°C for 24h to constant weight. The lung wet/dry weight ratio was then calculated. The pathologic changes of lung were observated by use of light microscopy and transmission electron micro- scopy technique.Results:1 The general situation of rats in this experiment: the rats in the sham group analepsied earlier than that in other groups and can act more actively. No abdominal dropsy and evil smelling were found when their abdomen were opened. The rats in the saline group analepsiaed later than that in the sham group, and then were depressed with inaction, piloerection, and tachypnea. When the abdomen was opened, bloody ascites and evil smelling were found and bowels looked edema. The cecum were darken in some rats. Compared with the saline group, the clinical manifestations in the rats of X groups were better.2 The change of the lung wet/dry (W/D) weight ratio in septic rats: The lung W/D was significantly increased in the NS group compared with that in Sham group at 6h after CLP (5.15±0.11 vs 4.54±0.16, P<0.01); The lung W/D was significantly increased in the X group compared with that in Sham group at 6h after CLP (4.7415±0.0818 vs 4.5433±0.1579, P<0.01); The lung W/D was significantly decreased in the X group compared with that in NS group at 6h after CLP (4.74±0.08 vs 5.15±0.11, P<0.01).3 The MMP-9 level in the serum: The serum MMP-9 level in NS group was significantly increased compared with that in sham group (11.5358±1.7278 vs 4.4667±1.0116,P <0.01); The X group was increased compared with sham group (7.4946±1.8549 vs 4.4667±1.0116, P <0.01); The level of X group MMP-9 was decreased compared with NS group (7.4946±1.8549 vs 11.5358±1.7278, P <0.05).4 The histopathological changes of lung tissue: light microscopic observasion: In Sham group, the lung structure including alveolar space and alveolar septum were normal; In NS group, the lung was heavy and swelling in dark red color with diffuse spots. The lung parenchyma was curmbly and rich in erythroic edema fluid. There were alveolar septum widening, capillary congestion, interstitial and alveolar edema, intra- alveolar hemorrhage and multiple inflammatory cell infiltration in the lungs of NS group. The histopathological changes in X group were not so serious as that in NS group. Electron microscopic observation: In Sham group, the edge of endothelial cells clearly, connecting closely, small amounts of swallowing vesicles in endochylema. In NS Group, pulmonary vascular endothelial cell membrane was dissolving, the edge was blurring, a lot of swallowing vesicles could be found in endochylema, and the endothelial cells gap was blurring. In X Group, there were some swallowing vesicles in endochylema of endothelial cell, and endothelial cells gap occurrenced.Conclusions:1 The animal model of sepsis was related with the expresson level of MMP-9, which damage the vascular endothelial cell, and cause acute lung injury;2 Xuebijing injection could protect the lung function, through decreasing in the MMP-9 level, relieving the damage of vas- cular endothelial cell, and improving pulmonary vasoperme- ability.
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