| Objective:To investigate the effect of N-acetylcysteine(NAC) on glucagons-like peptide-1(GLP-1), interleukin-6(IL-6) of liver and pancreas by insulin resistance in high-fat-diet rats.Methods:40 healthy male SD rats randomly divided into control group (NC group, n=10): normal diet; high-fat-fed group (HF group, n=30), feed with high-fat diet to construct rat model of insulin resistance. After feed for 12 weeks, Fasting plasma glucose(FPG), Fasting insulin(FIns), serum lipids, insulin sensitivity and insulin resistance index (HOMA-IR) were determined to confirm the construction of rat model. HF group randomly divided:high fat control group (HFN group, n=15), high fat+NAC group (HF+NAC group, n=15). NAC(300mg/kg.BW) was intragastric administration for 4 weeks, the other two groups were given the same volume of physiological saline. Liver were taken for histology changes. Rats GLP-1 level was measured by ELISA, IL-6 expression was measured by immunohistochemistry.Results:(1)The changes of rats’fasting lipids, glucose, insulin:the levels of HFN Fasting blood-glucose(FBG), Fasting blood insulin(FINS), Triglyceride(TG), Total cholesterol(TC) and Insulin sensitive index(ISI), HOMA-IR were significantly higher than that in NC group, the difference had statistical significance(P<0.05).The rates of HF+NAC group FBG、FINS、 TG、HOMA-IR were significant reduction than that in HFN group, the difference had statistical significance(P<0.05), while in HF+NAC group compared with NC group, there was no statistical difference (P>0.05);(2)Changes of the concentration of maleic dialdehyde(MDA) and the activity of superoxide dismutase(SOD):compared with HF+NAC group and NC group, the concentration of MDA increased, but the difference had no significant difference (P>0.05). HF+NAC group and NC group compared with HFN group, the concentration of MDA decreased, there had statistically significant (P<0.05). The activity of SOD in HF+NAC group was higher than in HFN group, the difference had significant difference (P<0.05).(3)Histological changes in liver tissue:the transverse sections of liver tissue of normal controls were soft,delicate, dark red in color by naked-eye observing; liver of HFN group were enlarged and had rounded edges, the transverse sections of liver were pale yellow and uplift slightly, as touching that having grasey feeling, and had the typical appearance of fatty liver; liver’s greasy feeling in HF+NAC group were alleviate,the volum were slightly larger, portion of the liver was close to the normal. Microscopically, arrangement of liver cells in group NC was normal; cells in group HFN arranged in disorder,and showed severe hepatic lsteatosis, hepatocyte swelling and turned round, cell nucleus were pushed to the side of lipid droplets visibly, some of liver cells filled with fatty and cell nucleus were disappeared; liver pathological in HF+ NAC group has improved, mainly with mild hepatic steatosis, lipid droplets in endochylema were reduced,and cytoplasm was adundant.(4)Changes of GLP-1 level:There were no significant difference in GLP-1 levels compared with NC group and HF+NAC group (P>0.05). GLP-1 levels were significantly higher of HF+NAC group and NC group than that of HFN, with the difference being statistically significant.(5) IL-6 positive staining cells were buffy fine particle mainly in the cytoplasm of liver and pancreatic cells.IL-6 was expressed highly in HF group; Bcl-2 expression score showed that IL-6 protein expression in NC group and HF+NAC group was reduced significantly compared with HFN group, with the difference being statistically significant(P<0.05); There were no significant difference between NC group and HF+NAC group (P>0.05).Conclusion The obese bats after high fat diet appearance insulin resistance, NAC relieves the insulin resistance in high-fat-diet rats through improving serum levels of GLP-1, reducing IL-6 activity, which has a protective effect on insulin resistance. |
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