| Non-alcoholic fatty liver disease (NAFLD), which is considered to be the hepatic injury related to insulin resisitance and hereditary susceptibility. It encompasses a spectrum of disorders ranging from simple steatosis to inflammatory steatohepatitis (NASH) and cirrhosis. Although the mechanisms are complicated, a large amount of information on the key mechanism is "Two Hits Theory". The first hit of steatosis, giving rise to the first lesions is caused by excess free fatty acids (FFA) in the liver, which are sterified to triglycerides (TG). These initial lesions make the liver vulnerable to aggressive factors of the second hit, which is caused by the oxidative stress and lipid peroxidation. This leads to the occurrence of lesions in the hepatocytes, inflammation and fibrosis, and consequently the evolution of hepatic steatosis to steatohepatitits. Oxidative stress, along with the insulin resistance, plays one of the essential roles in NAFLD pathogenesis. Therefore, treatment with different antioxidants (vitamin E, vitamin C, betaine, etc) has been used in prevent the process of NASH. However, there are no optimal drugs for NASH treatment so far. Some monomers extracted from Chinese herbs have the property of antioxidative stress, such as alkaloid, flavonoid, phenols. Matrine (MT), is an active ingredients of alkaloids, shows an remarkable effect in anti-inflammatory, antioxidant, anti fibrosis aspects.Cyclo-oxgenase2(COX-2) is a kind of membrane-binding proteins involved in prostaglandin synthesis, it can promote the inflammatory mediator release such as TNF-awith a chronic inflammatory stimulate, induce the liver inflammation cell infiltration. iNos also has high expression and activation with inflammatory stimulate, continuous catalyze and generate a lot of NO, produce toxic effects on liver cells. This study aim to observe the therapeutic effects of Matrine on the expression of COX-2and iNOS in rats with non-alcoholic fatty liver diseaseMETHODS:30Wistar rats (4-weeks,113～138g weight),were randomly divided into3groups, including the control (C, n=10), high fatty diet model (M, n=10), and matrine treatment groups (Ma, n=10). The groups of M and Ma were fed with a high-lipid diet for3weeks to induce non-alcoholic fatty liver model. After3weeks, the Ma group was administrated with Matrine36mg/kg/d for30days, and the control and model groups were administrated with normal saline. At the last day, rats were sacrificed. Then, the liver index, content of TC, TG in the liver, and the concentrations of TC, TG, HDL-C, LDL-C in serum were examined. In addition, histopathology analysis and NAS Score were performed. Furthermore, the expression of COX-2and iNOS were measured by real-time fluorescent PCR and the immunohistochemistry methods.RESULTS:High-lipid diet increased the content of TC, TG in liver, the concentrations of TC, TG, HDL-C and LDL-C in serum (P<0.05) and increased the expression of the COX-2and iNOS (P<0.01). Matrine decreased the liver index and the content of TC, TG in liver and the concentration of TC, TG, HDL-C and LDL-C in serum (P<0.05), arrest hepatic cell adipose degeneration, inhibit inflammation and hepatic cell ballooning degeneration (P<0.01), and decreased COX-2and iNOS significantly (P<0.01).CONCLUTION:Matrine is an effective therapeutic in treating rat non-alcoholic fatty liver disease through synergistical inhibition of COX-2and iNOS, resulting in preventing inflammation and oxidation. Objective:To investigate the serum level of liver-type fatty acid binding protein (L-FABP) and tumor necrosis factor-α (TNF-α) and their relationship with the function and inflammation of the liver in non-alcoholic steatohepatitis(NASH).Methods:50cases of NASH patients and32cases of healthy person as control group were included. B ultrasonic inspection has been performed to confirm the diagnosis of diffuse fatty liver. The height, weight, waist, and hipline of all subjects were measured, BMI and WHR were calculated. The level of serum L-FABP, TNF-a and related biochemical indexes were measured.Results:Compared with the control group, the serum level of ALT, AST, CHO, LDL-C, TG, BMI, WHR, hs-CRP, L-FABP and TNF-α in the NASH group was significantly increased (P<0.05). Spearman correlation analysis revealed that the level of L-FABP is positively correlated with TNF-α, CHO, LDL-C, ALT, UA, and hs-CRP (P<0.05), and the level of TNF-α is positively correlated with ALT, UA, and hs-CRP. Conclusion:L-FABP and TNF-α may play important role in the impaired function and inflammation in the liver of NASH. |
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