| ObjectiveTo observe the effect of fenofibrate on insulin resistance in severely scalded mice under the menotion of stress.Method1. Group with the scalded mice model Packeted130healthy Kunming mice (SPF)(Experimental Animal Center of Chinese Academy of Military Medical offers), male and female, body weight (30±2) g, rats aged6to8weeks. They are randomly divided into4groups after Libitum drinking, adaptive feeding one week,including low-dose group (Ⅰ), high-dose group (Ⅱ) and control group (Ⅲ) each40, normal10. The group of scald mice are reagented hair by30%TBSA back with6%Na2S, intraperitoneal injection of4%chloral hydrate (40mg· kg-1) anesthesia, anesthesia back upon satisfaction of mice placed100℃hot water hot12s,caused30%burn area Ⅲ°burn model (biopsy confirmed), immediately after intraperitoneal injection of sodium lactate Ringer (40mg· kg-1)2mL recovery. Modeled After modeled successfully daily morning8:00Ⅲ group received0.5mL· d-1saline, Ⅰ, Ⅱ group were to be30mg· kg-1· d-1,100mg· kg-1· d-a fenofibrate administered.2. Serum samples collected Experimental animals were fasted overnight, decapitated blood. Disposable normal10killed, Ⅰ, Ⅱ, Ⅲ group were sacrificed at1,3,7,14d,every point every group with10,2mL blood samples were collected at3000r/min,20min,4℃centrifugation, collected and saved0.5mL of serum-80℃for testing.3. Fasting blood glucose (FBG) were measured Measured FBG immediately at the time of the mice in each group sacrificed on day1,3,7,14with disposable blood glucose test strips and glucose meters.4. Serum insulin, TNF-a and FFA were determinated The serum were taken from the prepared-80℃refrigerator, first into4℃refrigerator thawing24h, and then moved to room temperature fou using. Using ELISA kit test serum insulin, TNF-a levels, using colorimetric detection FFA levels.5. Homeostasis model method (HOMA) insulin resistance index value is calculated insulin resistance index (HOMA-IR)-FBG (mmol/L) x Fins (mlU/L)/22.5.6. Liver tissue biopsy produced Mice in each group were killed after quickly cut the size of about1.0cm×1.0cm×0.2cm3of liver tissue (liver capsule included), placed in10%formalin solution, fixed, dehydrated, embedded in paraffin, sliced, HE staining under an optical microscope observation of liver histopathology.7. Statistical analysis Using SPSS18.0statistics and data processing. Measurement data to x+s that the use of single-factor analysis of variance (ANOVA), pairwise comparison method using LSD-t test, bivariate correlation analysis using linear correlation analysis, P<0.05was considered statistically significant.Result1. HOMA-IR values Comparison in each group at different time points The normal mice HOMA-IR is4.03±0.95. Mice in each group after the first burn1,3,7days HOMA-IR values were higher than the normal group,the HOMA-IR values of group Ⅰ and group Ⅱ were lower than the group Ⅲ (P<0.01), but the group Ⅰ and group Ⅱ mean difference at the same time point was not statistically significant (P>0.05). The first14days group Ⅰ and group Ⅱ HOMA-IR values close to the normal group, but the group Ⅲ HOMA-IR value is still higher than the normal group. In the same group at different time points between the mean differences were statistically significant (P <0.05). Respectively, compared with the normal group, always make differences (P <0.05).2. Changes in serum TNF-a levels The normal mouse serum TNF-a levels is (379.40±50.59) pg/mL. Group Ⅰ, Ⅱ, Ⅲin the first1,3,7days after injury serum TNF-a levels were higher than normal, serum TNF-a levels of group Ⅰ and Ⅱ were lower than the group Ⅲ (P<0.05or P<0.01), but the group Ⅰ and Ⅱ, the mean difference between groups at the same time point was not statistically significant (P>0.05). At the first14days, serum TNF-a of group Ⅰ and Ⅱ levels are close to the normal group, but the group III serum TNF-a levels are still higher than the normal group. Each group at different time points were statistically significant differences (P<0.05).3. Changes in serum FFA levels The normal mouse serum FFA values is (0.38±0.22) mmol/L. Group Ⅰ, Ⅱ, ⅢI mice in each group at1,3days after injury, serum FFA levels were higher than normal, serum FFA levels of group Ⅰ and Ⅱ were lower than the group Ⅲ (P<0.05or P<0.01), but group Ⅰ and group Ⅱ mean difference was not statistically significant (P>0.05) at the same point in time. The first seven days of each mouse serum FFA levels are still high, the first14days of group Ⅰ and Ⅱ, serum FFA levels close to the normal group, but the group Ⅲ serum FFA levels are still higher than the normal group. Each group at different time points were statistically significant differences (P<0.05).4. The correlation of serum TNF-a and FFA levels in each group scalded mouse Selecting the first three days of each group of mice measured serum TNF-a and FFA values, correlation analysis, we can see a correlation coefficient greater than0, indicating that There is a certain correlation between the two, and a positive correlation, but the P values were greater than0.05, indicating that the correlation coefficient was not statistically significant.5. Scalded pathological changes in the liver of mice Liver cells in normal mice showed normal state; scald control mice microscope partial liver cell swelling, blurred boundaries, light staining cytoplasm, there are different sizes of lipid droplets and partial fusion vacuole-like, with the first three days of the most obvious, shown in Figure2; low dose group of mice liver cell degeneration was significantly lighter than the control group. Analysis shows scalded mice with varying degrees of liver steatosis, fenofibrate intervention, improved liver steatosis.ConclusionMice in each group after the first burn1,3,7days HOMA-IR values were higher than the normal group, HOMA-IR values of group Ⅰ and Ⅱ were lower than group Ⅲ. Group Ⅰ, Ⅱ, Ⅲ serum TNF-a, FFA levels in each group of mice at different time points after injury were higher than the normal group, group Ⅰ were lower than group Ⅲ and group Ⅱ (P<0.05or P<0.01), but group Ⅰ and group Ⅱ mean difference was not statistically significant (P>0.05) at the same point in time. Each group at different time points were statistically significant differences (P<0.05). After scalded mice with varying degrees of hepatic steatosis, given fenofibrate intervention, hepatic steatosis improved. IR exists with a mouse burned, the most obvious of which the first and third days, while serum TNF-α and FFA levels were also significantly increased, and with the improvement of IR, TNF-α and FFA levels were also decreased, indicating non-Novo Bet you can reduce the severity IR index and serum levels of TNF-α and FFA scalded mice for further research to improve the stress state of the body after severe burns, provide the basis for reducing insulin resistance. |
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