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Clinical Significance Of Ghrelin,Adiponectin And Inflammatory Cytokines Detected In The Peripheral Blood Of Patients With NAFLD

Posted on:2011-01-06Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q WangFull Text:PDF
GTID:2144360305955273Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Non-alcoholic fatty liver disease(NAFLD) is getting more and more widespread and appears young-aged and globalized. Therefore, researches towards fatty liver shift the focus gradually from ALD to NAFLD. Non-alcohol fatty liver disease is an metabolic stress-related liver disease. NAFLD has already become the most important pathogen of chronic liver diseases and liver enzyme abnormalities in Western Europe, the United States, Australia and Japan. At present, the Chinese people are faced with rapidly growing weight problem.. Increasing of the obesity incidence, as well as non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and its related metabolic syndrome, will make a large percentage of Chinese people in danger of suffering from NAFLD in several dozens years. Insulin resistance may be a common metabolic defect to a variety of clinical chronic metabolic diseases, such as NAFLD,type 2 diabetes,hypertension and lipid metabolism disorder, hence, NAFLD and Metabolic Syndrome are becoming major health problems in china. However, the pathogenesis of NAFLD is so complex that no effective medicine has been developed for NAFLD treatment. Prevention and treatment of NAFLD has been not only a medical issue, but also a social problem.Adiponectin (adipone-ctin, Adp), as a newly discovered fat-derived cytokines, shows anti-SARS in a variety of cells, with improvement of insulin resistance, protect the endothelial function, anti-atherosclerosis,lowering blood sugar, blood fat and so on. As is known to all , hyperinsulinemia,insulin resistance and cytokine release which related with NAFLD , may form a vicious circle, promoting accumulation of fat in the liver and subsequent irritability damage. TNF-αis a pro-inflammatory cytokines ,substantial evidences show that TNF-αplays a improtant role in promoting fatty liver incidence and its progression. In contrast with TNF-α, adiponectin as an anti-lipid factor, shows functions in reducing the liver fat accumulation , and anti-SARS effect. Adiponectin and TNF-αdisplay the different effects in insulin sensitivity and inflammation , the balance between the two factors may contribure to the NASH morbidity.Ghrelin is one kind of endocardial ligand to growth hormone secretagogue receptor. The biological function of ghrelin is very widespread. Recent studies found that Ghrelin relates to the liver disease closely. I have already mentioned earlier that hyperinsulinemia,insulin resistance and cytokine release associate with NAFLD occurence. Many experiments proved that Ghrelin not only affects insulin release and the relationship between insulin sensitivity and insulin release,but also affects many obese factors, such as adiponectin and resistin,interacting with these factors, playing the influential role in obese as well as the NAFLD pathology process.At present,the research towards the association between NAFLD and the factors :Ghrelin,adiponectin,the inflammatory cytokines is a hot item. In this project, we detected the expression levels of Ghrelin, adiponectin,TNF-αand so on in peripheral blood to illustrate the relationship and the clinical significance between these factors and NAFLD.Objective: Discuss the relationship and the clinical significance between the expression of Ghrelin, adiponectin,TNF-αand non-alcoholic fat liver disease (NAFLD) peripheral blood.Methods: Detect the expression of Ghrelin, adiponectin, insulin and TNF-αin peripheral blood of the patients and healthy people with ELISA.Result: The expressions of Ghrelin and adiponectin in all experimental groups are significantly lower than those in the control group, the differences are statistically significant (P <0.01); The expressions of Ghrelin and adiponectin is not significant (P> 0.05) between the fatty hepatitis group,fatty liver combined IGT group and fatty liver combined dyslipidemia group, but the expressions of Ghrelin and adiponectin in these three groups are lower than those in the simple fatty liver group ,and the differences were significant (P <0.05). In contrast,the expression of TNF-a in all experimental groups are higher compared to control,which are statistically significant (P <0.01); The expression of TNF-a are not significant (P> 0.05) among the fatty hepatitis group,fatty liver combined IGT group and fatty liver combined dyslipidemia group; however, TNF-a expression in these three groups are higher than those in the simple fatty liver group ,and the differences are significant (P <0.05). All patients in experimental group bear higher BMI and HOMA-IR compared to those in control, and the differences are significant (P <0.01); Whereas, BMI has no significant difference (P> 0.05) in four experimental groups . In Fatty liver disease combined with impaired glucose tolerance group, HOMA-IR is higher than those in simple fatty liver group, fatty hepatitis, fatty liver combined dyslipidemia group ,among which the differences are significant (P <0.05); while HOMA-IR has no significant difference (P> 0.05) among the simple fatty liver disease group,fatty hepatitis and fatty liver combined dyslipidemia group. In the Multiple Stepwise Regression Analysis among the four experimental groups, take adiponectin as the dependent variable in order to Ghrelin, TNF-α, BMI, and HOMA-IR as independent variables-line, we find that adiponectin is negatively correlated with TNF-α, BMI and HOMA- IR ,but has positive correlation with Ghrelin. In the healthy control group, adiponectin showed no correlation between Ghrelin ,but adiponectin negatively correlated with TNF-α, BMI and HOMA-IR.Conclusion: The expression of Ghrelin obviously decreases in the peripheral blood of the non-alcoholic fat liver disease patient combind Glucose and lipid metabolism disorders , which is the result of a variety of factors. And possibly, the most important initiating agent is the metabolic anomalies , included metabolic imbalance of hormones significantly reducing he anti-SARS and liver cell protection functions of Ghrelin. It is Possibly especially important in the development of the NAFLD. The expressions of adiponectin in peripheral blood of all patients are obviously lower reduce comparing to the normal control groups, and the difference is statistically significant, with BMI and HOMA-IR was negatively correlated. Adiponectin has the anti-lipid effect, and can reduce liver fat accumulation, displaying anti-SARS effect as well. This indicates that there is a close relation between the low adiponectin and BMI,HOMA-IR, which paticipate in the morbidity of NAFLD and Metabolic Syndrome. It has a significant clinical significance to increase the density of adiponectin in the prevention of NAFLD developing process. TNF-αhighly expressed in all the patients, inversely correlated with Ghrelin and adiponectin, which may due to the second attacks in NAFLD progressing . TNF-αas a proinflammatory cytokine, plays important roles in promoting the occurence and progress of fatty liver.However, the adiponectin and Ghrelin show opposite functions in anti-fat,anti-SARS and insulin resistance improvement. Therefore, it has the guiding sense to study these cell factor imbanlance in interving NAFLD pathogenesis. We may envisage increasing the expression of endogenous Ghrelin, introducing exogenous Ghrelin, enhancing sensitivity of Ghretin and upregulating the levels of adiponectin receptors, developing adiponectin receptor agonists etc. To reduce imequilibrium of anti-inflammatory cytokines expression under the pathological state, figuring out the mechanism of its anti-SARS response, immunity and metabolism regulation, improving the nutritional state of the body so as to achieve the clinical application of therapeutic purposes.
Keywords/Search Tags:Ghrelin, adiponectin, NAFLD
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