The Influence Of Sepsis Rats Lung Tissue Permeability By Simvastatin Pretreatment

Objectives: Sepsis is a systemic illness caused by microbial invasion of parts of the human body. It is characterized by non-specific inflammatory responses with evidence of a microbial origin. Application of cecal ligation and puncture (CLP) rat model of sepsis process, make further observations of simvastatin pretreatment on permeability of rat lung tissue.Methods:Eighty healthy female wistar rats, weighing 200-250g (Hebei Medical University Experimental Animal Center, certificate number: 909908). Eighty rats were randomly divided into four groups,Ⅰgroup: normal control group (n = 8);Ⅱgroup: sham operation group (n = 24);ⅢGroup: sepsis model group (n = 24);ⅣGroup: simvastatin pretreatment befor make the CLP module group (n = 24). In addition to the normal group in all experimental groups rats were killed according to time points (6 hours, 24 hours and 48 hours) and keep samples, all groups were randomly divided into three groups of eight. This study application of cecal ligation and perforation (CLP) method make of rat sepsis model. Administration as follows: simvastatin pretreatment befor make the CLP module group for simvastatin(Merck Sharp & Dohme production, batch number: H19990366) 20mg/kg/d to feed into. normal control group, sham-operated group and sepsis CLP model group were fed into the 1ml sterile water for injection, Each group delivery times are 14 days. Normal control rats 14 days after administration of specimens from samples. Sepsis model group, sham operation group and simvastatin pretreatment befor make the CLP module group rats were in the modeling and surgery after the success of 6h, 24h, 48h specimens from samples. In rat lung tissue specimens from the left, said the lung tissue wet / dry ratio; the right side of the middle of specimens from lung specimens of vascular endothelial growth factor-a; specimens from serum specimens of vascular endothelial growth factor-a and intercellular adhesion molecule -1.Results:1 A general performance in ratsSham-operated rats can be transferred after about 1h awake, conscious and active state returned to normal, be free drinking water and eating, body temperature gradually returned to normal, no further demonstrated abnormal. CLP model group and simvastatin pretreatment befor make the CLP module group can be transferred to wake up after about 1.5h ,but apathetic, activity had dropped to just a small amount of eating and drinking, body curled up on ,the stimulus unresponsive, vertical hair , respiratory rate, rapid shallow or deep slow, rectal temperature increase or reduction of more than 1℃, abdominal distension obviously, they can have thin watery discharge. Cesarean section after the foul, and small bowel intestinal flatulence, cecal ligation side black, the surface with yellow pus, bloody exudate within the abdominal cavity, liver, lung, kidney, congestive enlargement was found in some lung tissue abscess formation visible on the surface. simvastatin pretreatment befor make the CLP module group compared with the performance of CLP model group.2 General eye view of lung tissue and lung tissue wet / dry ratioGeneral view of the naked eye: normal control group and the sham-operated rats lung tissues of pink, no congestion and edema; CLP model group and s simvastatin pretreatment befor make the CLP module group lung size increases, Chenganhongse, the surface can be seen varying degrees of congestion and edema, and some models even can see the surface of purulent exudate. CLP modules compared with the simvastatin pretreatment befor make the CLP module group performance of severity.Lung tissue wet / dry ratio: normal control group (4.4166±0.084) and sham-operated group 6h, 24h, 48h in rat lung tissue wet / dry weight ratio (4.2294±0.1963,4.4652±0.3542,4.6729±0.3941) had no significant difference in (P> 0.5); CLP model group, 6h, 24h, 48h lung tissue wet / dry ratio (5.8581±0.136, 6.0513±0.0683, 7.0582±0.6625) were significantly higher than sham-operated group and the normal group, the differences were statistical significance (P <0.05), and with time, the ratio was increasing trends; Simvastatin pre-treated CLP model group, 6h, 24h, 48h (4.3460±0.3294,3.9518±0.1297,4.9786±0.1175) lung tissue wet / dry ratios were significantly higher than sham-operated group and normal group (P <0.05), but the lower than the CLP model of sepsis group, the differences were statistically significant (P <0.05).3 The content of VEGF-a in serumThe normal control group (12.68±2.08) and sham-operated group 6h, 24h, 48h of serum VEGF-a concentration (11.81±1.83,10.52±2.17,10.91±2.07) had no significant difference (P >0.5); pus toxicosis CLP model in rats 6h, 24h, 48h of serum VEGF-a concentration (17.35±2.44,25.18±2.96,35.49±6.02) were significantly higher than sham-operated group and the normal group, the differences were statistically significant (P < 0.05), and with time, VEGF-a content was increased trend; Simvastatin pre-treated CLP model in rats 6h, 24h, 48h of serum VEGF-a concentration (11.88±1.31,13.36±4.68,12.05±2.75) were significantly higher than sham-operated group and the normal group, but lower than the septic Disease CLP model group, the differences were statistically significant (P <0.05).4 The content of ICAM-1 in serumThe normal control group (10.12±1.07) and sham-operated group 6h, 24h, 48h of serum ICAM-1 levels (11.88±1.09,11.23±1.08,11.07±1.29) had no significant difference (P>0.5); pus toxicosis CLP model in rats 6h, 24h, 48h of serum ICAM-1 levels (17.68±1.66,28.78±4.32,39.04±4.54) were significantly higher than sham-operated group and the normal group, the differences were statistically significant (P < 0.05), and with time, ICAM-1 levels on the rise; Simvastatin pre-treated CLP model group, 6h, 24h, 48h ICAM-1 levels (12.32±1.96,17.14±5.29,18.15±5.46) were significantly higher than sham operation group and normal group, but lower than the CLP model of sepsis group, the differences were statistically significant (P <0.05). 5 The content of VEGF-a in lung tissueThe normal control group(9.67±0.82) and sham operation group 6h, 24h, 48h (10.33±0.82,10.34±0.82,9.67±1.21)in rat lung tissue VEGF-a concentration had no significant difference (P>0.5), alveolar-free collapse, alveolar and pulmonary interstitial non-inflammatory cell infiltration, alveolar wall No thickening, non-telangiectasia, congestion and leukocyte mural phenomenon, no large areas of necrosis cells; CLP model of sepsis group of 6h, 24h, 48h (6.33±1.21,5.33±0.82,5.83±1.47)VEGF-a-positive cells were lower than the sham operation group and normal group, the difference was statistically significant (P <0.05), and with time, VEGF-a-positive cells showed a decreased trend in the alveolar space narrowing, alveolar wall thickening; pulmonary congestion, edema, inflammatory cell infiltration can be seen, and can be seen localized lung emphysema, local area shows a large number of necrotic cells. Simvastatin pre-treated CLP model group, 6h, 24h, 48h (3.33±1.37,3.01±0.89,6.95±2.90) VEGF-a-positive cells were lower than the sham operation group and normal group, but higher than the CLP model of sepsis group, the difference was statistically significant (P <0.05) , with the CLP model of sepsis group: alveolar collapse damage significantly reduced the extent and scope of the thickened pulmonary interval reduced congestion, edema was not obvious, inflammatory cell infiltration is reduced.Conclusions:1 Application of cecal ligation and puncture can make sepsis model.2 Sepsis in rat lung tissue congestion and edema, wet / dry ratio increased significantly in lung tissue VEGF-a were significantly decreased, while the serum ICAM-1, VEGF-a content was significantly increased, and with the time of sepsis extension of the more obvious the increase or decrease.3 Simvastatin pretreatment reduces sepsis after lung tissue wet / dry ratio, while significantly reducing l of serum ICAM-1, VEGF-a content, and to lung tissue VEGF-a concentration increased.