Effect And Mechanism Of Breviscapine On Rat Model Of Insulin Resistance Research

Objective: Establish the rat model with insulin resistance(IR) with high fat and sugar diets; observe the effect of breviscapine on IR rats and the expression of S6K1 and IRS-1 tyrosine phosphorylation in liver; explore the mechanism of breviscapine on IR.Methods: 50 SD male rats weighing 220±10g were randomly divided into the normal control group(normal diet, NC, n=10)and the IR model group(high fat and sugar diet). After 12 weeks, the rats in the IR model with high fat and sugar diets were randomly divided into the blank control model group(HFD), the high-dose breviscapine group(High) and the low-dose breviscapine group(Low) with 10 rats in each group. 1. At the end of 12 th week we took the Oral glucose tolerance test(OGTT), detected the fasting blood glues(FBG) and serum fasting insulin(FINS), calculated the insulin resistence index and evaluated whether the IR model was already established. 2. Dissiciate and weigh the liver, and then calculate the liver index. 3. Measure the the fasting blood glues(FBG) and serum fasting insulin(FINS) and calculate the insulin resistence index at the end of 14 th week. 4. Detect the pathological changes of liver tissue in rats with hematoxylin-eosin staining section. 5. Observe the fatty deposition and adipose infiltration in the liver with oil red O staining. 6. Detect the protein expressions of S6K1 and IRS-1 tyrosine phosphorylation in liver tissue in IR rats were with Western blot and IHC after the treatment of breviscapine.Results: 1. The result of OGTT showed the blood glucose values in the IR model group at all time points were significantly higher than the NC group and the difference was statistically significant(P <0.01); HOMA-IR of IR model group was significantly higher than NC group and the difference was statistically significant(P < 0.01). The IR model was ready after 12 weeks. 2. Liver index of HFD rats was significantly higher than that of NC group and there was a significant difference(P <0.01). Compared with the HFD group, the liver index in the breviscapine High and Low group decreased and there was a significant difference(P <0.05). 3.The amount of HOMA-IR in HFD group was significantly higher than that in NC group(P < 0.01); The amount of HOMA-IR in High group and Low group was significantly lower than that in HFD group(P<0.01). 4.The result of HE showed that liver cells in HFD group were fatty degeneration obviously compared with that of the NC group. After the treatment of breviscapine, the number of fatty degeneration liver cells in High group and Low group significantly reduced compared with that of the HFD group. 5. Oil red O staining showed that there was obvious fat deposition of the liver tissue in the HFD group(P <0.01); compared with the HFD group, the fat deposition in the High group and Low group significantly improved. 6. The result of Western blot and IHC showed that the expression quantity of S6K1 protein in High group and Low group was lower than that of HFD group((P<0.01) and the expression quantity of IRS-1 tyrosine phosphorylation in High group and Low group was higher than that of HFD group((P<0.01, P<0.05).Conclusion: 1. SD rats fed with high fat and high sugar successfully established rat model of IR. 2. Breviscapine has a protective effect on IR rat liver.3. Breviscapine can improve insulin resistance in IR rats. The mechanism may be associated with down-regulated expression of S6K1 protein and the increasing IRS-1 tyrosine phosphorylation levels.