| ObjectiveIn this study,pterostilbene(PTE)was used to interve high-fat and high-sugar diet supplemented with streptozotocin(STZ)-induced type 2 diabetes mellitus(T2DM)rats to investigate the effect of PTE on liver injury in T2DM rats.Materials and methodsThere were 120 male 4-week-old SPF-grade SD rats.The rats were randomly divided into the normal control group(n=20)and the model group(n=100)after one week of adaptive feeding.The rats in the model group were fed with high-fat and high-sugar feed,while the rats in the normal control group were fed with standard diet.The model group was induced by a single intraperitoneal injection of 40 mg/kg 1%STZ according to the weight of rats after 4 weeks of high-fat and high-sugar diet.Normal control rats received the same amount of citric acid-sodium citrate buffer.After 72 h of STZ injection,the fasting blood glucose(FBG)of rats was?11.1 mmol/L,and the FBG levels of the rats did not return to normal after one week was identified as a successful model for type 2 diabetic rats.According to T2DM rat modeling standards,eighty-three were successed,and the modeling success rate was 83%.After establishing the T2DM rat model,randomly selected rats and divided them into the T2DM control group,the low-dose PTE group(20 mg/kg),the medium-dose PTE group(40 mg/kg),and the high-dose PTE group(80 mg/kg),there were 20 rats in each group.Rats in normal control group and T2DM control group were given sodium carboxymethylcellulose solution only,and rats in other groups were given a corresponding doses of PTE solution dissolved in sodium carboxymethylcellulose solution according to body weight once a day.The rats were sacrificed in batches at 6 and 12 weeks of intervention,blood was collected from the abdominal aorta and livers were collected.Measuring FBG,fasting serum insulin(FSI),total cholesterol(TC),triglyceride(TG),and low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),interleukin-6(IL-6),IL-1?,serum tumor necrosis factor-?(TNF-?),serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels,and levels of nuclear factor-?(NF-?B),IL-6,inhibitor of nuclear factor-?B ?(I?B?),phosphorylated inhibitor of nuclear factor-?B ?(?-I?B?)protein in livers were also measured and livers' histomorphology were observed.SPSS 25.0 was used for statistical analysis and the test level was ?=0.05.Results(1)General appearance of the rats:the general appearance of the T2DM control group was worse than that of the normal control group,and the increased urine volume,slow or even decreased body weight were also observed(P<0.05).After 6 weeks and 12 weeks of PTE intervention,the status of body weight of T2DM rats was improved,but the difference was not statistically significant(P>0.05).(2)FBG and FSI in rats:The levels of serum FBG and FSI in T2DM rats were significantly higher than those in the normal control group(P<0.05).After 6 weeks of PTE intervention,the levels of FBG and FSI in the PTE intervention groups were significantly lower than those in the T2DM control group(P<0.05),and the reduction effect was most significant in the low-dose PTE group.After 12 weeks of PTE intervention,the FBG level of the middle-dose PTE group was significantly lower than that of the T2DM control group(P<0.05),and there was no significant difference in FBG levels between the low-dose,high-dose PTE groups and the T2DM control group(P>0.05);while the FSI levels of the PTE intervention groups were significantly lower than that of the T2DM control group(P<0.05),and the reduction effect of the middle-dose PTE group was the most significant.(3)Blood lipid levels in rats:The levels of serum TC,TG and LDL-C in the T2DM control group were significantly higher than those in the normal control group,while the serum HDL-C levels were significantly lower than that in the normal control group(P<0.05).After 6 weeks of PTE intervention,TC,TG,LDL-C levels in the low-dose PTE group and TC,LDL-C levels in the medium-dose PTE group,and TC level in the high-dose PTE group were significantly lower than those in the T2DM control group(P<0.05);after 12 weeks of PTE intervention,the levels of TC,LDL-C in the low-dose PTE group,the levels of TC,TG,LDL-C in the medium-dose PTE group,and the level of LDL-C in the high-dose PTE group were significantly lower than those in the T2DM control group(P<0.05).The level of serum HDL-C in the PTE intervention groups was not significantly different from that in the T2DM control group during the intervention.(4)Serum inflammatory factors in rats:The serum IL-6,IL-1? and TNF-? levels in the T2DM control group were significantly higher than those in the normal control group(P<0.05).After 6 weeks of PTE intervention,the levels of inflammatory factors in the PTE intervention groups were significantly lower than that of the T2DM control group(P<0.05);after 12 weeks of PTE intervention,the levels of IL-6,TNF-?in the low-dose PTE group,and the level of IL-6 in the medium-dose PTE group,and the levels of IL-6,IL-1? and TNF-? in the high-dose PTE group were significantly lower than those in the T2DM control group(P<0.05).(5)Rats liver function enzyme indexes:The serum ALT and AST levels of the T2DM control group were significantly higher than those of the normal control group(P<0.05).After 6 and 12 weeks of PTE intervention,the serum ALT and AST levels of the PTE intervention groups were significantly lower than those of the T2DM control group(P<0.05).(6)Protein levels in rat livers:The levels of NF-?B,IL-6 and p-I?B? protein in livers of T2DM control group were significantly higher than that of normal control group,and the level of I?B? protein was significantly lower than that of normal control group(P<0.05).After 6 and 12 weeks of PTE intervention,the levels of NF-?B,IL-6,p-I?B? protein in the PTE intervention groups were significantly lower than that in the T2DM control group,and the levels of I?B? protein were significantly higher than that in the T2DM control group(P<0.05)(7)Pathological morphology of rat livers:Compared with the normal control group,the T2DM control group had a disordered hepatic cord structure,hepatic cell swelling,and local inflammatory cell infiltration and bleeding.After 6 and 12 weeks of PTE intervention,compared with the T2DM control group,the inflammatory cells,necrotic cells,and hemorrhage of the rat liver tissue of the PTE intervention groups were reduced,and the hepatocyte morphology was improved.Conclusions(1)PTE intervention can reduce FBG,FSI,blood lipid levels and the levels of serum inflammatory factors in T2DM rats.(2)PTE intervention can reduce serum ALT and AST levels in T2DM rats;meanwhile,PTE ameliorate liver injury in T2DM rats may be related to I?B/NF-?B/IL-6 signaling pathway.(3)PTE intervention can ameliorate liver tissue lesions in T2DM rats by reducing inflammatory cells,necrotic cells,and bleeding. |
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