| Objective: ALI models of white rabbits were replicated with lipopolysaccharide (LPS)injected so as to observe the pathophysiology changes in rabbits and investigate themechanism of acute lung injury and the protective effect of Fufangkushen injiection inALI.Methods: Twenty-one male New-Zealand flap-eared white rabbits were randomlyassigned to three groups: control group (A), injury group (B) and therapeutic group (C).There are seven animals in each group. All animals were anesthetized with20%urethane (5ml/kg) though peritoneal cavity. Aniamal in group A receviedsaline(4m1/kg). Group B were intravenously injected LPS(720g/kg) dissolved insaline over a period of5minutes, and injected saline later. The volume of saline ofgroup B was also4m1/kg. Group C were identical to group B but receivedFufangkushen(4m1/kg) the same time to LPS.The parameters were measured asfollows:During the experimental course, arterial blood pressure, arterial blood gases,serum markers (SOD, MDA, IL-33, IL-35), plasma markers (t-PA, PAI-1) weremeasured at0h,0.5h,1h,2h and4h respectively. Lung homogenate markers includingSOD, MDA, IL-33, IL-35, t-PA, PAI-1were also detected. After rabbits sacrificed at4h,the wet-to-dry lung weigh ratio was measured and pathological changes of lung tissuewere observed by light microscope.Results: The observed targets in group A are stable during the experiment and there areno statistic different between the group A,group B and group C.1.The bloodpressure,PaO2and OI in group B were definitely lower than that in group A (P <0.01)after injecting LPS at the time point of0.5h. The tendency of the three parameters asmentioned above in group C were also decreased significantly, but the levels werebetween group A and group B(P <0.01or P<0.05).2.During the process of experiment, Serum IL-33level in group B was significantly increased (P <0.01). Lung homogenateIL-33levels compared with group A also increased (P <0.01).IL-33level in both serumand lung homogenate in group C also tended to increase, but less than the ascendingtrend in group B (P <0.05).3. IL-35in group B decreased gradually and the differentcompared to group A were significantly (P <0.01). The level of IL-35in group Cdecreased and there are significant differences in the extent of the decline than in groupB (P <0.01). IL-35in lung homogenate in group B is lower than in group A (P <0.05),Group C was slightly higher than in group B but was significantly decreased comparedwith group A (P <0.05)4. The activity of SOD downward trend in group B wasstatistically significant compared with group A (P <0.05). Group C serum SOD activitykeep a downward trend during the experiment, but between group A and group B, andwere significantly different compared with group B (P <0.05). SOD activity in lungtissue in Group B was lower than in group A and group C (P <0.01), beweent groupAand group C there were non-statistically significant.5. After LPS injection, serum MDAvalues in group B and group C gradually increased (P <0.01), serum MDA values ingroup C were lower than group B at the time points of1h,2h,4h, and there arestatistically significant (P <0.01). MDA content in lung tissue in group B wassignificantly higher than that in group A and group C (P <0.01). There are nostatistically significant in Group C compared with group A.6. After intravenousinjection of LPS in group B, Plasma PAI-1levels were significantly increased at all timepoints (P <0.05or P <0.01). PAI-1levels of group C increased slightly but weresignificantly lower than group B (P <0.05or P <0.01). PAI-1levels in lung tissue ingroup B were significantly higher than group A (P <0.01) and C group (P <0.05), groupC PAI-1content were between groups A and B.7. t-PA content in group B, weresignificantly increased at all time points after intravenous injection of LPS (P<0.01).Between t-PA content in group C and in group A there are no significant differences butcompared with group B there were statistically significant (P <0.01). t-PA content inlung tissue of Group B was significantly higher than group A and group C (P <0.05),Group C and Group A showed no statistically significant,and the content in group C were between A and Group B.8. The wet-to-dry lung weight ratio: lung tissue wet-to-dry ratio was significantly higher than that in group A and group C (P <0.01), Group Cwas significantly higher than group A (P <0.05) but significantly lower than that ingroup B (P <0.01).9. Pathological observation: Group B in lung tissue is easy to see thetypical pathology of ALI performance, compared with Group B, Group C animalsdamage significantly reduced, the structure of groupC was similar to the group A.Conclusion: ALI model of New Zealand white rabbits can be copied by a singleinjection of LPS (720g/kg). Pro-inflammatory and anti-inflammatory imbalance,oxidative damage and lack of anti-oxidation, imbalance of coagulation and fibrinolysisall involved in LPS-induced ALI incedence. Fufangkushen may have something to dowith the protective effect of ALI by antagonizing inflammation, improving antioxidantcapacity and balancing coagulation and fibrinolysis. |
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