ABSTRACT
Objective To investigate the effect of low molecular weight heparin on lung Injury complicated by severe acute pancreatitis and explore its mechanism.Methods Ninety Wistar rats were randomly divided into 3 groups,namely sham operation (SO) group,acute necrotizing pancreatitis (ANP) group,low molecular weight heparin treatment (LH) group.4％ sodium taurocholate was injected into the pancreatic duct to induce ANP model.Subcutaneous low molecular weight heparin (10 U/100 g body weight) was injected in the LH group,the equivalent amount of normal saline was injected in the SO and ANP group.After 6,12,24 h,rats were sacrificed respectively,pancreas and lung tissues were harvested to observe the pathological changes and the pathological changes were scored;and the changes of TLR4 and VEGF protein expression in lung tissue was determined by immunohistochemical method.Serum and lung levels of IL-6,IL-l0,TNF-α were determined by ELASA method.Results The pancreas and lungs tissues were normal in SO group,diffuse hemorrhage,necrosis and a large number of inflammatory cells infiltration was observed in pancreas tissue in ANP group.Lung alveolar wall rupture,interstitial hyperemia,edema,a large number of infiltrating neutrophils could be seen in lung tissue in ANP group.The pancreas and lungs tissues injuries were significantly alleviated.The pancreas and lungs pathological scores of ANP group at 12 h were 6.34 ± 1.09,7.01 ± 1.16,and those were 5.48 ± 0.86,6.24 ± 0.86 in LH group,the values in LH group were significantly lower than those in ANP group (P ＜ 0.05),and there was a positive association between lung and pancreas scores (r =0.812,P ＜ 0.01).The expressions of TLR4,VEGF,IL-6,TNF-o,IL-10 in lung tissue of ANP group at 12 h were 0.68 ± 0.10,0.50 ± 0.11 and (2617.2 ± 485.3),(1603.1 ± 519.7),(608.3 ±137.5)pg/g,which were 0.61 ±0.09,0.41 ±0.06 and (2398.5 ±503.7),(1302.4±389.8),(753.2 ±100.0) pg/g in LH group,and the expressions of TLR4,VEGF,IL-6,TNF-α in LH group were significantly lower than those in ANP group,but the expression of IL-10 was significantly up-regulated,and the difference between the two groups was statistically significant (P ＜ 0.05).The serum levels of IL-6,TNF-α,IL-10 in ANP group at 12 h were (184.3 ± 45.7),(289.7 ± 60.4),(143.2 ± 30.4) μg/L,which were (143.8 ±31.8),(256.4 ±40.7),(189.3 ± 50.9)μg/L in LH group,and the levels of IL-6,TNF-α in LH group were significantly lower than those in ANP group,but the expression of IL 10 was significantly increased,and the difference was statistically significant (P ＜ 0.05).The expression of TLR4,VEGF in lung tissue was positively associated with the degree of lung injuries (r =0.524,0.503,P ＜ 0.05).Conclusions Low molecular weight heparin may improve lung injury complicated by ANP.The mechanism may involve inhibiting the expression of TLR4 and VEGF protein,IL-6,TNF-α,and up-regulation of the expression of IL-10.
ABSTRACT
Objective To investigate the treatment effects of dahuang gancao decoction on lung Injury complicated by acute necrotizing pancreatitis and explore its mechanism. Methods 90 Wistar rats were randomly divided into 3 groups, namely sham-operated group (SO), ANP group (ANP), dahuang gancao decoction treatment group (DG). 4% sodium taurocholate was injected into the pancreatic duct to induce ANP. Dahuang gancao decoction(0.25 g/ml) 0.6 ml/100 g weight was gavaged in the DG group, the same volume of normal saline was gavaged in the SO and ANP group, which was repeated 12 h later. After 6 h, 12 h, 24 h, all rats were sacrificed, pancreas and lung tissues were harvested to observe the pathological changes and the pathological changes were scored. IL-6, IL-10, TNF-α levels of serum and lung tissue were measured,and the changes of toll-like receptor 4 (TLR4) expression in lung tissue was determined by immunohistochemical method. Results 12 h after ANP induction, the serum levels of IL-6 in SO, ANP, DG group were (14.4±4.0)pg/ml, (171.4 ±41.3)pg/ml, (156.9 ±34.7)pg/ml; the serum levels of IL-10 were (13.7 ±4.5)pg/ml, (120.5 ±23.7)pg/ml, (148.3 ±44.4)pg/ml; the serum levels of TNF-α were (22.4 ±4.7)pg/ml, (261.3 ±51.4)pg/ml, (235.3 ±45.9)pg/ml; the lung tissue levels of IL-6 were (257.3 ±55.9)pg/ml,(2578.3 ±403.0)pg/ml,(2370.0 ±491.0)pg/ml; the lung tissue levels of IL-10 were (80.8 ±20. 8)pg/g, (642.0 ± 107.3)pg/g, (695.3 ± 151.7) pg/g, the lung tissue levels of TNF-α were (207.6 ±98.6)pg/g, (1769.1 ±635.6) pg/g, (1401.1 ±450.5) pg/g; the pancreas pathological scores were 0, 7.00 ±1.33, 6.30 ± 0.95; the lung pathological scores were 0, 6.30 ± 1.42, 5.60 ± 0.97; the expressions of TLR4in lung tissue were 0.09 ± 0. 03, 0.59 ± 0. 09, 0. 52 ± 0. 08. The values in the ANP and DG groups were significantly higher than those in SO group (P < 0. 01 ); except for IL-10, all values in the DG groups were significantly lower than those in ANP group (P < 0.05); there was a positive association between lung and pancreas scores (r =0.807, P<0.01), and lung score was positively associated with the expression of TLR4(r = 0.519, P < 0.01 ). Conclusions Dahuang ganeao decoction may quickly improve lung injury complivated by ANP. The mechanism may involve inhibiting the expression of TLR4 and down-regulating the expression of IL-6, TNF-α, up-regulating the. Expression of IL-10.