Effect Of Expression Of PMN Cytochrome C On SAP With Combined Treatment Of Traditional Chinese And Western Medicine

Background and objective:SAP is a disease with acute onset and rapid progress, which can lead systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome(MODS) at early stage, parts of patients with the complication of Hemorrhage of pancreas,necrosis and secondary infection and so on. So the mortality rate is very high. SIRS is the prophase of clinical manifestation for SAP, It finally could cause the SAP to get worse.Polymorphonuclear neutrophil (PMN) is the first line of defense system, and it plays an important role in development of inflammation. The life period of PMN is very short in the circulation, the ageing PMN will die by means of apoptosis under the normal condition, it is identified and cleaned by macrophage.It prevents tissues from injury which is caused by inflammatory mediator and toxic substances which are released by PMN necrosis. If the apoptosis of PMN is delayed, it will make inflammatory response worse gradually. Owing to the PMN moving from peripheral circulation to inflammation site, the number of PMN in tissues increase and release mounts of inflammatory cytokines, which lead to SIRS and makes SAP worse ultimately. Cytochrome C is an interrelated protein of apoptosis, which is found the first protein of mitochondrial inner membrane and plays an very important role in apoptosis. Under stimulus of the signal of apoptosis, cytochrome C is released from mitochondrion to cytoplasm and induces apoptosis. According to research the expression of cytochrome C when the PMN apoptosis, it can reveal parts of mechanisms that the relations beween the delayed of PMN apoptosis and cytochrome C. This experiment is to study the effect of traditional Chinese medicine Dachengqi DecoctionN Dexamethasone and combination of the two drugs on expression of cytochrome C protein in SIRS induced by SAP rat model.Methods:The SAP model of SD rat was established by retrograde injection of 1.5%concentration of sodium deoxycholate into common pancreatic duct. SD rats (n=75) were randomly divided into sham operation group(SO),severe acute pancreatitis SIRS model group(SIRS),Dachengqi Decoction treatment group(DCQT),Dexamethasone treatment group(DEX) and Dachengqi Decoction associates with Dexamethasone treatment group(ZXY). dose of Sodium Chloride(1ml/100g,by intragastric administration)for SO group and SIRS group;dose of the Dachengqi Decoction was lml/100g(by intragastric administration),while dose of Dexamethasone was 1mg/100g(intraperitoneal injection).the treatment group in two hours and after producing the model with a re-delivery in 12 hours.Model samples were collected after 24h for detection.Pathological changes and pathology score of pancreat were observed with microscope in each group; Detected the content of serum amylase and the differences of levels of interleukin 6 by ELISA; Used western blotting to detect differences of cytochrome C expression level between each group.Results:1. Pathological changes of pancreas in each group:(1)compared with SO group pathological changes in SIRS Group were significantly obvious (edema:1.90±0.06vs0.70±0.12;inflammation:1.80±0.11vs0.05±0.03;hemorr hage:1.95±0.06vs0;necrosis:2.85±0.09vs0;vacuolization:2.20±0.10vs0,P<0. 01);(2)compared with the SIRS group, various improvement in treatment groups can be seen with statistical significance(P<0.05),particularly in ZXY group(edema:1.30±0.06vsl.90±0.06;inflammation:1.20±0.01vsl.80±0.11;he morrhage:0.80±0.04vsl.95±0.06;necrosis:2.00±0.05vs2.85±0.09;vacuolizat ion:1.30±0.08vs2.20±0.01,P<0.01).2. The differences of levels of serum amylase and interleukin 6:(1)Compared with SO group, the levels of serum amylase and interleukin 6 in SIRS group were significantly increased (P<0.01); (2)Compared with SIRS group, the levels of serum amylase and interleukin 6 were significantly decreased in treatment groups (P<0.01);(3) Compared within treatment groups:compared with DEX and DCQT group, the levels of amylase and interleukin 6 were significantly decreased in ZXY group (P<0.05); compared with DCQT group, the levels of amylase and interleukin 6 had no significantly difference in DEX groups.3. Detected different levels of cytochrome C expression by western blotting:(1) Compared with SO group, the expression of cytochrome C in SIRS group was significantly different (0.41±0.01vs2.28±0.30, P<0.01);(2) Compared with the SIRS group:the expression of cytochrome C was increased and different in DEX and DCQT groups, while the ZXY group PMN expression of cytochrome C were significantly different (2.20±0.27vs0.41±0.01,P< 0.01);(3) To compare within treatment groups:Compared with the DEX and DCQT groups, the expression of cytochrome C in ZXY group were significantly different(P<0.05); Compared with DCQT group, the expression of cytochrome C had no significantly difference in DEX groups.Conclusions:Compared with SO group, SIRS group has more serious pathological changes in the pancreas. The treatment groups have varying degrees of improvement, with the most obvious effect in ZXY group, implying that Dachengqi Decoction alone or Dexamethasone alone has less significant effect on pathological changes of rat pancreas than joint Application of Western and Chinese Medicine. With the established of SAP model in rat, the levels of serum amylase and interleukin 6 in model groups were significantly increased and had various improvement in treatment groups, while ZXY group had obvious improvement. Expression of cytochrome C in SIRS Group significantly decreased, the treatment groups increased in varying degrees, in which Chinese and Western Medicine has better effect on expression of cytochrome C than the single treatment group,suggesting that the expression of cytochrome C decreased significantly in the SAP mode was possible one of important factors, which cauce PMN to apoptosis delayed. The delayed apoptosis of PMN rise to a large number of neutrophils accumulated in the body and release excessive mediators of inflammation and cytokine, which makes the SAP a deterioration conditions. Therefore, traditional Chinese and western medicine may be effective way to restrain the delayed apoptosis of PMN and become treatment of SIRS caused by SAP.