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Molecule Mechanism Of Disfunction Of PMΦ Phagocytizing Apoptotic PMN In SIRS And Combined Treatment Of TCM With Westermedicine

Posted on:2009-10-18Degree:MasterType:Thesis
Country:ChinaCandidate:K R QuFull Text:PDF
GTID:2144360245464969Subject:Traditional Chinese Medicine
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Background and objective:Systemic inflammatory response syndrome (SIRS) is the prophase of clinical manifestation for many disease which will chang into multiple organ dysfunction syndrome (MODS) or MSOF. It finally could cause these diseases to get worse. Acute pancreatitis is one of the important disease causing SIRS. Polymorphonuclear neutrophils (PMN) is the main effector cell in the development of inflammatory, it plays an important role in SIRS, for which influence occurrence, development and turnover. PMN will die by means of apoptosis under the normal condition, it is identified phagocytized and cleaned by macrophage phagocytosis. If apoptotic PMN will not be phagocytized and cleaned by macrophage promptly, the toxic substance released by disintegrated apoptotic PMN causes tissue trauma and through infernal circle makes SIRS to aggravate.So, cleaning apoptotic PMN at the right moment is important moderately. mCD14 is one of the receptors of macrophage identifing and phagocytizing apoptotic cells. In this study, the aim is to study the relation between the expression levels of macrophageocyte's mCD14 of mRNA and protein and the capability of MΦphagocytizing apoptotic PMN in animal model of SAP leading to SIRS. To investigate the function and mechanism of traditional Chinese drug Yinchen Chengqi Decoction, Dexamethasone and Yinchen Chengqi Decoction+Dexamethasone.Methods:The SAP/SIRS model of SD rat was established by retrograde injection of 1.5% concentration of sodium deoxycholate into common biliopancreatic duct. Rats (n=75) were divided at random into sham operated group, SAP/SIRS group, Yinchen Chengqi Decoction group (therapeutic dose:1ml/100g,by PO), Dexamethasone group (therapeutic dose: 1mg/100g, by injection in abdominal cavity).All the rats were killed at 24 hours after operation. Pathological examination and indexes of SIRS were measured. The pathological alteration of pancreas was examined with microscope to scoring tissue.The phagocytosis function of macrophage was performed by the test of MPO. The different levels of mCD14 mRNA expression in different groups were analyzed by semiquatitative reverse transcriptase polymerase chain reaction(RT-PCR).The express- ion levels of mCD14 protein were detected by using immunocytochemistry.Results:1.Pathological alteration of pancreas with microscope:compared with sham operated group, the pathological alteration of pancreas of SAP/SIRS model group is significantly changed (edema:3.60±0.22 vs 0.30±0.06, inflammation:2.80±0.15 vs 0, hemorrhage:2.20±0.18 vs 0, necrosis:2.81±0.25 vs 0, P﹤0.01);compared with SAP/SIRS model group,all treatement groups′pathological pancreas are amended with different degrees(P﹤0.05), and then Yinchen Chengqi Decoction + Dexamethas- one group is significantly improved (edema:3.10±0.14 vs 3.60±0.22, P﹤0.05, inflammation:1.50±0.13 vs 2.80±0.15, hemorrhage:0.30±0.16 vs 2.20±0.18,nec- rosis:1.30±0.48 vs 2.81±0.25, P﹤0.01).2.Comparing the phagocytosis function of macrophage:(1).compared with sham operated group, the phagocytosis function of macrophage decreased obviously in SAP/SIRS group (2.10±0.6 vs 3.6±0.5, P﹤0.01);(2).compared with SIRS model group:the phagocytosis function of macrophage increased in the Yinchen Chengqi Decoction group (2.5±0.4 vs 2.10±0.6, P﹤0.05), the phagocytosis function of macrophage increased in the Dexamethasone group (2.9±0.3 vs 2.10±0.6, P﹤0.05);(3).compared with different treatment groups:the phagocytosis function of macrophage increased significantly in Yinchen Chengqi Decoction group (3.0±0.2 vs 2.5±0.4 vs 2.9±0.3, P﹤0.01).3.Comparing the expressions of mRNA and protein:(1).compared with sham operated group, the expression of mCD14 which is macrophageocyte′s gene was significantly decreased in SAP/SIRS group (mRNA level:0.63±0.04 vs 0.80±0.13, P﹤0.01, protein level:16.7% vs 80.0%, P﹤0.05);(2).compared with SIRS model group:the expression of mCD14 which is macrophageocyte′s gene was significantly increased in Yinchen Chengqi Decoction group (mRNA level:0.63±0.04 vs 0.68±0.09, P﹤0.05), nonetheless the protein level was not obviously increased (16.7% vs 50.0%, P﹥0.05). The expression of mCD14 which is macrophageocyte′s gene was significantly increased in Dexamethasone group (mRNA level:0.63±0.04 vs 0.71±0.20, P﹤0.05), nonetheless the protein level was not obviously increased (16.7% vs 62.5%, P﹥0.05). The expression of mCD14 which is macrophageocyte′s gene was significantly increased in Yinchen Chengqi Decoction + Dexamethasone group (mRNA level:0.63±0.04 vs 0.79±0.21, P﹤0.01,protein level:16.7% vs 75.0%, P﹤0.05);(3).compared with different treatment groups:the expression of mCD14 which is macrophageocyte′s gene was significantly increased in Yinchen Chengqi Decoction + Dexamethasone group than others treatment groups (mRNA level:0.79±0.21 vs 0.71±0.20,0.79±0.21 vs 0.68±0.09, P﹤0.05), nonetheless the protein level was not obviously increased (75.0% vs 62.5%,75.0% vs 50.0%, P﹥0.05). Compared with Yinchen Chengqi Decoction group, the expression of mCD14 which is macrophageocy te′s gene was not obviously increased in Dexamethasone group (mRNA level:0.71±0.20 vs 0.68±0.09, P﹥0.05,protein level:62.5% vs 50.0%, P﹥0.05).Conclusions:Compared with sham operated group, the pathological alteration of pancreas in SIRS model group was changed at extent severely. All treatment groups were differently improved, but Yinchen Chengqi Decoction + Dexamethasone group was most obviously effective. It is implied that only single drug isn't more better than Yinchen Chengqi Decoction + Dexamethasone group, and it has more limitations. The expression of mCD14 at mRNA and protein levels which is macrophageocyte′s gene was significantly decreased in SIRS model group. All treatment groups were differentl- y increased, but Yinchen Chengqi Decoction + Dexamethasone group leaded to the expression levels up-regulation of mCD14 which is macrophageocyte′s gene(in the levels of mRNA and protein)in SIRS. These are implied that macrophageocyte′s cell membrane and its internal environment maybe be changed, which damage the functions of macrophage at extent, especially the function of all kinds of receptors on the macrophage. In inflammatory, the expression levels down-regulation of mCD14 which is macrophageocyte′s gene (in the levels of mRNA and protein), which will lead to decrease the function of macrophage phagocytizing and cleaning apoptotic PMN. This would make PMN collect excessively, thereby pathogenetic condition could all the more aggravate. So, combination of TCM (traditional Chinese medicine) with Western medicine which can containment disease condition of SIRS maybe a new clinic therapy way.
Keywords/Search Tags:severe acute pancreatitis, SIRS, macrophage, mCD14, phagocytosis
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