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Study On Protective Effects Of Recombinant Human Bikunin On Acute Liver Injury

Posted on:2009-07-17Degree:MasterType:Thesis
Country:ChinaCandidate:W YangFull Text:PDF
GTID:2144360242980121Subject:Medical and Biological Engineering
Abstract/Summary:
These years the study on the mechanism and prevention of liver injury has became hot spot in biology medical research in the world. The mechanism of Liver damage is very complex,and there are mang factors related to it .The protective effects of various drug on liver injury have been proved in the recents years.which focus on antioxidants, membrane stabilizers,cytokines network regulator, apoptosis inhibitor and some Chinese traditionalmedicine,etc. Bikunin as a pancreatic protease inhibitor with a variety of biological functions, a large number of results demonstrated that Bikunin plays an important role in the treatment of acute pancreatitis, lung injury, the adjuvant treatment of shock, reduce complications and improve cardiopulmonary bypass surgery prognosis, and so have an important role, But the study of the effects of Bikunin on liver injury in less comprehensive,and it was only confirmed that Bikunin had protective effects on ischemia-reperfusion liver injury The present study demonstrated that Bikunin had protective effects against CCl4 induced acute liver injury,and explored the mechanism of the proteceive effects in aspects of free radical metabolism and inflammatory cytokines.To evaluate the protective effects of Bikunin on CCl4 induced mice acute liver injury,we established experimental acute liver injury mice model using CCl4 followed by injecting Bikunin to mice intra-peritoneal.Further more,we compared the effects of rhBikunin with natural extracted Bikunin.The results are as follows.1. Compared with the normal group,the serum ALT and AST levers of the model group were significantly higher (P <0.001), The low, medium and high-dose rhBlkunin group compared with the model group, were significantly lower the serum ALT and AST levels (P<0.05,P<0.01,P<0.001)of liver injury mice,and the ALT liver of high-dose group is lower than that of control group (P<0.05).2. Compared with the normal group: the serum SOD activity model group was significantly lower (P<0.01).The SOD activity of each group of different dose of rhBikunin dose group was higher than that of the model group of liver injury mice significantly (P<0.01 ). The effects of high-dose group are similar to that of natural extracted Bikunin.3. Compared with the normal group, the lever of malondialdehyde (MDA) in liver was significantly higher (P <0.01).Compared with the model group the MDA level in serum of each rhBikunin group was significantly lower (P <0.05 ), excepet that of rhBikunin low-dose group.The MDA level in liver serum of rhBikunin high-dose group is similar to that of control group.4.Compared with the normal group , the lever of NOS in liver was significantly higher (P <0.01).Compared with the model group the NOS level in surm of each rhBikunin group was significantly lower (P <0.05), The NOS level in liver serum of rhBikunin high-dose group is lower than that of control group (P <0.05).5.Compared with the normal group: the lever of IL-6 in liver was significantly higher (P <0.01).Compared with the model group the IL-6 level in surm of each rhBikunin group was lower (P <0.05), The IL-6 level in liver serum of rhBikunin high-dose group is similar to that of control group (P <0.05).6.Histological odservaton showed that low, medium and high-dose of rhBikunin can reduce the liver cell necrosis and reduce the infiltration of inflammatory in vary degrees cells. At the same time, the low, medium and high-dose of rhBikunin could maintain the integrity of cell membrance and structure,and reduce swelling of mitochondria in ultrastructure.. Electron microscope observation showed the same change to that of light microscope.These results indicated that Bikunin had significant protective effects on acute mice liver injury when injected peritoneal confirming the protencial usage of Bikunin in multiple organ failure and revealing the new pharmacological effects of Bikunin.Moreover,we demonstrated that rhBikunin had the same effect to natural extracted Bikunin.
Keywords/Search Tags:Bikunin, Hepatic injury, CCl4
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