The Effect of Fatty Liver Disease on the Expression of RXFP1 and CTGF Genes in Cardiac Tissue of Wistar Rats

Background & Aims: Performing physical activity and having a healthy body is one of the most essential life needs of people with fatty liver. In recent years, studies have been performed on the relationship between fatty liver and arthrosclerosis. The results of these studies indicate the relationship between the Non-alcoholic fatty liver and arthrosclerosis of coronary artery disease. Non-alcoholic fatty liver disease is associated with a sedentary lifestyle and poor eating habits around the world Fatty liver is associated with an increased risk of cardiovascular disease and the formation of atherosclerotic plaques in the carotid arteries and coronary artery stenosis can affect extracellular matrix factors such as CTGF and RXFP1, which play a role in the formation or non-formation of fibrosis. Studies have shown that fatty liver disease can be effective in causing atherosclerotic changes in arteries and increasing the thickness of the carotid artery as an indicator of atherosclerosis, which can be seen even in mild degrees of fatty liver. Relaxin in all parts of the body can have different expressions of RXFP1 receptor in different arteries, so in rats this receptor is strongly expressed in aortic endothelial cells and RXFP1 activates cAMP, cGMP and cAMP signaling pathways in ERK1 / 2 endothelial cells On the other hand CTGF is mainly synthesized by liver cells in the liver and is strongly induced in liver fibrosis CTGF is induced by fibroblast TGF-β cells and mediates the growth and secretion of extracellular matrix. These results indicate that CTGF is the mediator of many TGF-β-probiotic activities Therefore, the aim is to investigate the effect of this disease on two extracellular matrix genes of the heart. Methods: In this experimental study, 24 male Wistar rats weighing 200-250 g were randomly divided into 3 groups: control, healthy and fatty liver steatosis. The control group was initially performed in the victim and tissue study And the two healthy and fatty liver groups spent two weeks in the same condition There was a healthy group from the beginning to the end of the study and they did not receive any intervention. Mice in the fatty liver group received oral tetracycline at a dose of 100 mg / kg at a dose of 1.5 ccs per mouse for two weeks. The average weight of the mice was 300 g, of which 100 mg / kg was used for 3 mice, of which 100 mg was dissolved in 4.5 cc and each rat was gavaged 1.5 cc. Fatty liver was modified by measuring liver enzymes (SGPT) and a number of biochemical variables. At the end of the second week, rats two groups were healthy and fatty liver48 hours after the last day (10 to 12 hours of fasting), the studied rats in each group were anesthetized by intraperitoneal injection of a mixture of 10% ketamine at a dose of 50 mg/kg and 2% xylosin at a dose of 10 mg/kg. became were sacrificed and heart tissue sample were taken to test for RXFP1 and CTGF gene expression. In each group, tissue analysis was performed by Real Time PCR technique. First, primer design was performed and then total RNA was extracted from tissues and converted to cDNA. Then cDNA was Replicated by PCR and examined for the expression of the mentioned genes. Results: After the second week and examining expression level of RXFP1 and CTGF genes between control, healthy and fatty liver groups, ANOVA test results showed that the expression level ofRXFP1 and CTGF genes (p = 0.0001 and p = 0.0001, respectively) In the fatty liver group, significantly increased compared to the healthy and control groups Considering the value of P<0.05, the null hypothesis that there is no significant difference between the level of RXFP1 in different research groups was rejected with 95% confidence. The results between the steatosis group and the other two groups were significant in increasing the level of RXFP1 gene expression. Therefore, it can be said that in the presence of fatty liver, the expression of RXFP1 gene increases in the heart tissue of male rats in order to inhibit fibrosis. Also, in terms of significance, the results between the steatosis group and the other two groups were significant in increasing the level of CTGF gene expression. Therefore, it can be said that in the presence of fatty liver in the steatosis model, the CTGF gene expression increases in line with the increase in cardiac fibrosis. Overall, our results showed that with the onset of fatty liver disease, both connective tissue growth factors and relaxin increased in the heart, and an increase in connective tissue growth factor indicates cardiac tissue damage, which can lead to heart tissue fibrosis. Therefore, these findings can help new therapies aimed at modulating the effects of CTGF and the use of RXFP1 as a new direction for further clinical studies. Our other findings showed that with induction of fatty liver, the level of RXFP1 in heart tissue increased from the beginning and did not change until the end of the two weeks. The expression level of RXFP1 gene in steatosis fatty liver groups (BS, CS) was significantly higher than the other 2 groups on the other hand the increase in connective tissue growth factor (CTGF) in this study was probably to produce extracellular matrix and compensate for their degradation, and the increase in RXFP1 was to prevent collagen deposition in ECM connective tissue growth factor (CTGF) in cardiac tissue increased sharply, such that its rate increased up to 7 times in the first two weeks compared to the control group, and this increase continued until the end of the two weeks, that increased 10 times However, this method should be considered with more caution because high expression of CTGF increases the level of fibronectin, collagen I and III proteins in the extracellular matrix, followed by myocardial infarction Conclusion: The fatty liver model of steatosis increases the expression of cardiac CTGF gene and fibrosis, and also increases the RXFP1 gene, which has anti-fibrosis activity. CTGF (CCN2) in response to tissue damage initiates signaling pathways of connective tissue regeneration Therefore, and cardiac tissue fibrosis. RXFP1, which is a component of the extracellular matrix and is most commonly expressed in aortic endothelial cells exerts most of its physiological effect on the cardiovascular system through NO (Nitric oxide).