The Effect Of Fasudil On Sepsis-Induced Acute Lung Injury And Expression Of HMGB1 In Lung Tissue

Objective: To observe the effect of Fasudil on sepsis-induced mouse lung injury and the expression of TNF-α and HMGB1’s volume in mouse lung tissue.Methods: 48BALB-C mice were randomly divided into three groups: sham, CLP, CLP+Fasudil. We used a mouse model of endotoxemia that consists of cecal ligation with puncture(CLP). Fasudil was applied by intraperitoned injection at 18 h and 30 min before CLP(CLP+Fasudil). The sham mice received open surgery only(sham). Blood and BALF were collected and lungs were harvested at 6 and/or 24 h for analysis.Results:(1)The CLP and FAS have obvious pathological manifestations in postoperative such as the decline of activity ability, mental fatigue, shortness of breath, anorexia, Vertical hair, the decline of hair gloss, the increase of the eye secretions,the indifference to the stimulation. But the symptoms of the FAS are milder than the CLP. The Sham are milder or no to various pathological changes.(2)HE dyeing pathological section of the lung tissue showed the CLP and FAS has obvious inflammatory changes sucn as inflammatory cell infiltration, interstitial edema, vessel hyperemia and hemorrhage, but the FAS have more obviously improved than the CLP.(3)The total protein concentration in the BALF of each group is(0.19±0.03)mg/ml,(0.21±0.03)mg/ml,(0.43±0.11)mg/ml,(0.29±0.05)mg/ml,(0.72±0.13)mg/ml and(0.41±0.09)mg/ml, the total protein concentration of the FAS is always lower than the CLP in the same time point(P<0.05).(4)The concentration of TNF-α in the BALF of each group is(39.17±2.11)pg/ml,(38.22±2.24)pg/ml,(50.59±4.85)pg/ml,(41.89±4.72)pg/ml,(72.83±12.70)pg/ml and(52.84±5.84)pg/ml; The concentration of HMGB1 in the BALF of each group is(941.30±160.93)pg/ml,(1008.48±121.45)pg/ml,(1783.37±147.26)pg/ml,(1242.89±226.78)pg/ml,(2332.83±171.74)pg/ml and(1825.65±156.12)pg/ml, Comparing with the concentration of the two inflammatory factor, the FAS is always lower than the CLP in the same time point(P<0.05).(5)The concentration of TNF-α in the serum of each group is(29.47±2.52)pg/ml,(30.24±1.20)pg/ml,(48.66±5.16)pg/ml,(38.11±6.71)pg/ml,(34.81±4.58)pg/ml and(30.03±3.90)pg/ml; The concentration of HMGB1 in the serum of each group is(22.97±3.80)pg/ml,(30.66±4.78)pg/ml,(38.96±7.63)pg/ ml,(29.18±5.66)pg/ml,(77.32±15.07)pg/ml and(62.06±11.59)pg/ml, comparing with the concentration of the two inflammatory factor, the FAS is always lower than the CLP in the same time point(P<0.05).(6)The optical density ratio of TNF-αm RNA in the lung tissue of each group is 0.01±0.00, 0.02±0.00, 0.17±0.03, 0.06±0.02, 0.57±0.03 and 0.38±0.05; The optical density ratio of HMGB1 m RNA in the lung tissue of each group is 0.30±0.16, 0.42±0.04, 0.63±0.11, 0.44±0.11, 0.78±0.07 and 0.53±0.10. comparing with the expression volume of the two inflammatory factor, the FAS is always lower than the CLP in the same time point(P<0.05).(7)comparing with the immunohistochemistry section of each group,the number of the HMGB1(+)cell of the FAS is much less than the CLP in the same time point(P<0.05).Conclusions:(1)the CLP model caused by sepsis can recrease the infiltration of inflammatory cells in lung tissue causing acute lung injury, at the same time enhance blood, TNF-α and HMGB1 expression in lung tissue.(2)Fasudil can reduce the cecal ligation and puncture-induced lung injury of the mice and relieve the expression of TNF-α and HMGB1 in lung tissue.