The Relationship Between Hepatoma And Insylin Resistance

Objects:In this article we will analyze the different level of insulin resistance in the patients with different liver pathology. And establish a model of hepatitis in nude mouse, a model of liver fibrosis in nude mouse and a model of liver cirrhosis in nude mouse. We also will analyze the growth of liver cancer in the difference liver pathological status, and the relation of insulin resistance and liver oncogenesis.Methods:1. To collect48liver cancer patients,56liver cancer with cirrhosis patients,34cirrhosis patients and30normal patients who with normal blood glucose level. Examine the patients height, weigh, smoker and alcohol history, BMI, hepatitis history, blood routine and glucose, blood function of liver and renal, blood tumor marker, RIA method to examine the level of C-peptide and insulin, ELISA method to examine the level of resistin.2. To inject the CCL4and olive oil into the celiac as test group. Meantime inject the olive oil into the abdomen as control group. The test group and control group are divided separately into three groups (2w,7w,12w group). To analyze the status of nude mouse after injection. To examine the pathology of liver after terminate the mouse.3. To establish a model of hepatitis, a model of liver fibrosis and a model of liver cirrhosis in nude mouse. We implant high or low metastasis liver cell on the lesion of the liver. To observe the growth of different liver cancer types in the different pathological status, ELIS A method was used to examine the level of insulin and resistin and analyze the degree of insulin resistance. To observe the pathological change in mouse livers, immunohistochemistry method was used to examine the expression level of resistin in different liver status. We testified the insulin resistance as a reason of tumor oncogenesis by test the expression level of IRS-2by Real time-PCR.Results: 1. There are no difference in height, weight, smoker and alcohol history, BMI, hepatitis history, blood routine and glucose, blood function of renal in the test group and control group. The level of ALT, AST, GGT in test group were higher than those in control group. The level of biliary and albumin are no difference in all patients. There were no difference in liver cancer patients and liver cancer and cirrhosis patients with positive AFP. There are no difference in the three test group with HBV(+) or anti-HCV(+), BMI and blood glucose were no difference in the four group. Fasting insulin and c-peptide are higher in the three test group than in control group(P<0.05). And Fasting insulin and c-peptide are higher in the liver cirrhosis group than in cancer and liver group(P<0.05) We calculate the index of HOMA. The index are higher in the three test group than in control group(P<0.05). And higher in the liver cirrhosis group than in cancer and liver group(P<0.05) We also examined the resistin.The results were same with the insulin or c-peptide.2. The test groups are obviously anorexia and lethargy. In the early stage the average weight of test group improved slower than the control group. The weight improved in2week test group3.6±1.8g, The weight improved in2week control group6.4±0.7g(P<0.05), The weight improved in7week test group11.5±0.8g, The weight improved in7week control group12.7±1.4g(P>0.05), The weight improved in12week test group13.2±1.2g, The weight improved in12week control group15.4±2.1g(P>0.05)。The index of liver function:ALT(IU/L)2week test group86.5±23.6.2week control group30.4±4.7, AST(IU/L)2week test group92.8±37.4、2week control group27.7±8.5, GGT(IU/L)2week test group168.4±39.522week control group37.9±7.1。ALT(IU/L)7week test group65.3±9.6、7week control group, AST(IU/L)7week test group59.8±8.1、7week control group29.4±7.2, GGT(IU/L)7week test group98.7±8.47week control group35.3±6.2。ALT(IU/L)12week test group48.7±6.6、12week control group19.8±5.3, AST(IU/L)12week test group45.4±7.2、12week control group22.6±5.8, GGT(IU/L)12week test group71.6±10.312week control group42.7±6.8。3. The average volume of the tumor in the test group are bigger than that of the control group.The results of the insulin tested by ELISA in2w,7w,12w test group were higher than the control, P<0.001; The results of the resistin tested by RIA in2w,7w,12w test group were higher than the control group, P=0.000。 The index of HOMA in insulin resistance are2w test group are0.1509±0.1497,2w control group0.053±0.0495, P<0.001;7w test group0.2735±0.1782,7w control group0.0395±0.0161, P<0.001;12w test group0.4777±0.3591,12w control group0.0655±0.0637, P<0.001. The expression level of resistin in test group are2w test group20%,7w test group55.6%,12w test group75%.IRS-2are high expressed in normal liver, and gradually lower in hepatitis and liver fibrosis, lowest in cirrhosis certificate the insulin resistance in the lesion of the liver. IRS-2is high expressed in liver cancer.Conclusion:1. Liver is the target organ of insulin resistin. The chronic inflammation of liver will result in insulin resistance of the body. Insulin resistance is accompanied with liver cancer, liver cirrhosis, liver cancer and cirrhosis. Insulin resistance is maybe one reason of liver oncogenesis. Insulin resistance results in liver cirrhosis which is one reason of liver cancer.2. We can use the method of injecting the CCL4and olive oil into the celiac to establish the model of hepatitis or fibrosis or cirrhosis in nude mouse. To make the foundation of implanting human liver cancer in the different hepatic status.3. the liver tumor grow rapidly in nude mouse liver cirrhosis than in liver fibrosis, and grow rapidly in nude mouse liver fibrosis than in hepatitis. The different volume of the liver cancer is correlate with the status of the liver pathology. Insulin resistance maybe the reason of the liver fibrosis and cirrhosis which result in liver cancer. Insulin resistance maybe the reason of the liver cancer.