ABSTRACT
OBJECTIVE: To investigate total glucosides paeony (TGP) on the expression phosphorylated extracellelar signal regulated kinase 1/2(p-ERK1/2), Toll-like receptors 4(TLR4) and Toll-like receptors 9(TLR9) in rats with nonalcoholic fatty liver disease (NAFLD) induced by fructose and high-fat feed. METHODS: SD rats were divided into normal group and test groups. The rats in test groups were fed with fructose and high-fat feed for 10 weeks totally to induce the test model. After 6 weeks the model was established, the rats were divided into four groups randomly, the model group (NAFLD), the metformin group (Met, 200 mg · kg-1), the low-dose TGP group(TGP-L, 100 mg · kg-1) and the high-dose TGP group(TGP-H, 200 mg · kg-1) (n=10). Four weeks later all the rats were killed and checked the indexes such as serum fasting blood glucose(FBG), fasting insulin(Fins), insulin sensitivity index (ISI), total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), free fatty acids (FFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S-transferase (GST) and liver index. The expression p-ERK1/2, TLR4 and TLR9 were inspected by Western-blot. RESULTS: Compared with the normal group, the rats in test groups were with the high levels serum FBG, insulin, TC, LDL-C, TG, FFA, ALT, AST, GST, liver index, p-ERK1/2, TLR4 and TLR9 (P 0.05). CONCLUSION: By downregulating the expression ERK1/2, TLR4 and TRL9, TGP can improve abnormal glucose and lipid metabolism and insulin resistance, enhance insulin sensitivity and ameliorate liver function in rats with NAFLD induced by fructose and high-fat feed.
ABSTRACT
<p><b>OBJECTIVE</b>To study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism.</p><p><b>METHOD</b>Adult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI) were counted. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were measured also. Livers were weighed and collected to be observed the pathological changes.</p><p><b>RESULT</b>Compared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously (P < 0.01), ISI were decreased (P < 0.01), FFA, TG, TC, LDL-C were increased (P < 0.01), HDL-C were decreased (P < 0.05); the content of MDA were increased (P < 0.05), the activities of SOD were decreased (P < 0.01); AST, ALT and ChE were increased (P < 0.05, or P < 0.01), the pathological changes of liver fat were severe (P < 0.01). In glucosides of paeony group and metformin group, hyperinsulinaemia and insulin resistence were resisted (P < 0.05, or P < 0.01); the levels of FFA, TG, TC, LDL-C were decreased and HDL-C were increased (P < 0.05, or P < 0.01); the activities of AST, ALT, ChE were decreased (P < 0.05, or P < 0.01) and SOD were increased (P < 0.01). The contents of MDA were decreased (P < 0.05). The levels of FBG and 2 hBG in metformin group were decreased but in total glucosides of paeony group were not decreased obviously.</p><p><b>CONCLUSION</b>Total glucosides of paeony may protect liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.</p>