Font Size: a A A

The Therapeutic Effect Of Ulinastin On Acute Lung Injury In Neonatal Rat And Probable Mechanisms

Posted on:2008-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:W F GaoFull Text:PDF
GTID:2144360215989008Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Objective:Ulinastain (UTI)is protease inhibitor get out from human urine.It has many pharmacologic actions.For example:It can inhibit PMNs to assemble and set out protease , stable lysosomal membrane, inhibit and clear the production of overdose of hyperoxide.It can also get out of oxyradical and inhibit inflammatory factors to be set out. There are more and more researches about it . LPS is main component of endotoxic of Gram-Negtive bacillus and is often used to make model of ALI.In this study,the newborn rat was injected LPS to make an animal modal of acute lung injury. We measured the wet weight/dry weight (W/D), the oxidative stress, the expression of MMP-9 and inflammation factor in lung tissue in order to search the medicine to protect acut lung injury,We infused UTI to the newborn rats and analysis the alteration of above index to explore the therapeatic effect of UTI on acute lung injury in newborn rats and probable mechanisms.By the research we will provide theory for the clinical cure .Methods: The animal modle of acute lung injury was established by injecting LPS into abdominal cavity of newborn rats.After injection of LPS the oral lip of newborn rat appeared cyanosis.Their frequency of respiratory turned very high .Thirty healthy rats of 7-8 days weigting 15g-20g and not considered sex were divided into three groups by random:Control group, LPS injury group, UTI treat group.Then they were killed after four hours and the level of W/D,SOD,MDA,MPO,TNF-a.and IL-8 were measured,the expression of MMP-9 in lung tissue was examined by immunochemistry,meawhile The histopathological changes of lung tissue were observed.Results:1 Gross examination: in injury group,the lung volume became swelled and had severe congestion. In UTI treat group there were slight alterations compared with the changes in injury group. There was no alteration in lung tissue in control group.Microscopic exam: Rats of control normal had a normal structure.In injury group, the alveolar cavity became narrowing.There was blood in capillary and inflammatory cell infiltrated . In UTI treat group there were slight alterations compared with the changes in injury group.2 Changes of the content of pathological mechanism grade:The content of pathological mechanism grade in control group was 0,in injury group was 2.5±0.3 (P<0.05compared with control group),in UTI treat group was 2.2±0.2 (P<0.05compared with injury group).3 Changes of the content of W/D ratio:the W/D ratio in control group was 4.95±0.44,in injury group was 5.62±0.57 (P<0.05compared with control group),in UTI treat group was5.40±0.39 (P<0.05compared with injury group). 4 Changes of the content of MDA:The content of MDA in control group was 8.20±0.92 nmol/mgprot,in injury group was 11.14±1.62 nmol/mgprot (P<0.05compared with control group), In UTI treat group was 9.50±1.51nmmo/mg prot(P<0.05 compared with injury group).5 Changes of the content of SOD: The content of SOD in control group was 91.93±4.36 NU/mg prot, in injury group was 52.50±3.31NU/mg prot (P<0.05compared with control group),in UTI treat group was59.54±2.27 NU/mg prot (P<0.05compared with injury group).6 Changes of the content of TNF-a: The content of TNF-a in control group was 57.07±8.94 pg/ml in injury group was 220.90±15.15pg/ml (P<0.05compared with control group),in UTI treat group was199.96±20.85pg/ml (P<0.05compared with injury group).7 Changes of the content of IL-8:The content of IL-8 in control group was 0.43±0.17pg/ml,in injury group was 1.32±0.22pg/ml (P<0.05compared with control group),in UTI treat group was 1.06±0.19pg/ml(P<0.05compared with injury group).8 Changes of the content of MPO: The content of MPO in control group was 0.97±0.46u/g,in injury group was 9.72±3.81u/g (P<0.05compared with control group),in UTI treat group was 6.39±2.69u/g (P<0.05compared with injury group).9 Changes of the content of MMP-9: The intensity of MMP-9 in control group was3.71×10-4±0.90×10-4, in injury group was5.83×10-4±1.28×10-4 (P<0.05compared with control group),in UTI treat group was 4.78×10-4±1.05×10-4(P<0.05compared with injury group).Conclution: Application of Ulinastatin to ALI could not only maintain the activity of SOD and reduce the level of MDAbut also cut down the activity of MPO and MMP-9, so the production of oxyen-derived free radidicals was get down and the injury from PMNs was relieved.By inhibiting the generation and release of inflammatory cytokine Ulinastatin can relieve the inflammatory reaction.Thereby the application of UTI developed the effect of cure for the newborn rats.
Keywords/Search Tags:neonate, acute lung injury(ALI), ulinastatin(UTI), superoxide disputes(SOD), tumor necrosis factor-α(TNF-α), matrix metalloproteinase-9(MMP-9)
PDF Full Text Request
Related items