| Objective In this study,a type 2 diabetic rat model was established by feeding high-fat and high-sugar diets combined with intraperitoneal injection of streptozotocin(STZ).After 6 weeks and 12 weeks intervention by gavage,the effects of Pterostillbene on the blood glucose,blood lipids,serum insulin,serum superoxide dismutase(SOD),malondialdehyde(MDA),Peroxisome Proliferator-activated receptor ?(PPAR?)and PI3 K Protein expression on adipose tissue were observed,thus explore the effect of pterostilbene on glucolipid metabolism of type 2 diabetic rats and its protective effect on pancreas tissue.Methods After one week adaptive feed,one hundred and forty four-week-old SD male rats were randomly divided into control group(n=20)and model group(n=120).The control rats were given ordinary feed feeding,model group rats fed with high-fat and high-sugar diet.At 4 weeks,control group were injected with citric acid buffer in the abdominal cavity,and rats model group were given an intraperitoneal injection of STZ(40 mg/kg)solution.After 72 hours,the fasting blood glucose in rats was ?11.1 mmol/L and the rats had symptoms of polydipsia,polyphagia and polyuria.After one week,the blood glucose level in rats did not return to normal,which means that the model was successful built.After modeling,the rats were randomly divided into type 2 diabetes mellituse(T2DM)control group(n=20),low-dose pterostilbene group(n=20),middledose pterostilbene group(n=20),high-dose pterostilbene group(n=20)and rosiglitazone group(n=20).The normal control group and the T2 DM control group were given intragastric administration of sodium carboxymethyl cellulose once a day at a fixed time.The low-dose group of pterostilbene(20 mg/kg),the middle-dose group of pterostilbene(40 mg/kg),the high-dose pterostilbene group(80 mg/kg)and the rosiglitazone group(5 mg/kg)were intragastrically administered once a day at a fixed daily dose.10 rats were randomly selected from each group.Rats fasted for 12 h in the night and drank water freely.Anesthesia with chloral hydrate and blood collection from the abdominal aorta,detection of fasting blood glucose(FBG),serum fasting insulin(FINS)),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low desaturase lipoprotein-cholesterol(LDL)-C),serum superoxide dismutase(SOD),and serum malondialdehyde(MDA)levels.Adipose tissue was separated and the expression of PPAR? and PI3 K protein in adipose tissue were detected.Pancreatic tissue was observed for histomorphology.SPSS 21.0 was used for statistical analysis of experimental data,and the test level was ?=0.05.Result(1)Effects on body weight and urine volume: After a 6 and 12 weeks of intervention,the body weight of rats in the T2 DM control group,the low-dose pterostilbene group,the middle-dose pterostilbene group,the high-dose pterostilbene group,and the rosiglitazone group were lower than those in the normal control group(P<0.05);the weight of rats in the low-dose pterostilbene group was higher than those in the T2 DM control group,the middle-dose pterostilbene group,the high-dose pterostilbene group and the rosiglitazone group,and the difference was not statistically significant(P>0.05).When fed with high-fat and high-sugar diet for 4 weeks,the urine output of model rats with type 2 diabetes was higher than that of the normal control group(P<0.05);After intraperitoneal injection of STZ,the amount of urine of type 2 diabetic rats increased significantly,which was higher than that of the normal control group.At the 6th week of intervention,the urine volume of the rats in the low-dose pterostilbene group,the middle-dose pterostilbene group,the high-dose pterostilbene group,and the rosiglitazone group was significantly lower than that of the T2 DM control group(P<0.05),and was higher than that of the normal control group(P<0.05);at the 12 th week of intervention,the urine outpu of rats in T2 DM control group,low-dose pterostilbene group,middle-dose pterostilbene group,high-dose pterostilbene group,and the rosiglitazone group was higher than normal control group(P<0.05).(2)Effect on pancreas tissue morphology: The pancreatic tissue was observed under an optical microscope.At the 6th and 12 th week of gavage,the islets of the normal control group were oval in shape,regular in structure,clear in cell boundary,uniform in size,full in shape,and arranged closely.At the 6th week of intervention,the islets of T2 DM control group were irregular,unclear boundaries,sparse arrangement,structural disorder,and vacuolization of cells;At the 12 th week of intervention,the number of pancreatic islets decreased and part of the islet cells swelled.At 6 weeks of intervention,the pancreatic islets in the rosiglitazone group were round,well organized,with clear boundaries,a few cells were swelled,and the cytoplasm was loose.After 12 weeks of intervention,the cytoplasm appears loose vascularization;the pathological changes of pancreatic tissue in the intervention group of pterostilbene were between the normal control group and the rosiglitazone group.(3)Effects on blood glucose and insulin: At the 6th week of intervention,FBG levels in rats of low-dose pterostilbene group(26.31±2.86 mmol/L),middle-dose pterostilbene group(27.64±3.87 mmol/L),and rosiglitazone group(26.05±1.39 mmol/L)were lower than that in T2 DM control group(31.15±2.21 mmol/L)(P<0.05).At the 12 th week of intervention,the FBG levels in low-dose pterostilbene and middle-dose pterostilbene groups were comparable to those in T2 DM control group,and there was no significant difference between the two groups(P>0.05).There was a significant difference(P<0.05)between the T2 DM control group and the rosiglitazone group(21.81±22.35 mmol/L).At the 6th week of intervention,the serum insulin levels in rats of low-dose pterostilbene group(41.16±9.79?IU/m L),middle-dose pterostilbene group(53.06±25.26 ?IU/m L),high-dose pterostilbene group(63.08±16.14 ?IU/m L),and rosiglitazone group(30.46±17.21 ?IU/m L)were significantly lower than that in the T2 DM control group(97.26±21.77 ?IU/m L)(P<0.05).At the 12 th week of intervention,the serum insulin level in rats of low-dose pterostilbene(31.73±13.04 ?IU/m L),middle-dose pterostilbene(44.10±30.20 ?IU/m L)and rosiglitazone(21.81±22.35 ?IU/m L)were significantly lower than that of the T2 DM control group(113.41±52.0 ?IU/m L)(P<0.05),but still higher than the control group.(4)Effects on blood lipids: After successful establishment of type 2 diabetic rat model,the levels of TC,TG,and LDL-C were significantly higher than those of control rats(P<0.05).At 6th and 12 th weeks of intervention,the levels of TC,TG and LDL-C in rats of the low-dose pterostilbene group and the rosiglitazone group were lower than those in the T2 DM control group(P<0.05),but were still higher than those in the control group.The TC level in the low-dose group was lower than that in the high-dose group(P<0.05),and higher than that in the control group(P<0.05),at the 12 th week of intervention.(5)Effects on oxidative stress indicators: After the successful establishment of type 2 diabetic rat model,serum SOD levels were significantly reduced.At the 6th week of intervention,serum SOD levels were lower in rats treated with low dose of pterostilbene and rosiglitazone compared with rats in T2 DM control group(P<0.05).At 12 th week of intervention,serum SOD levels in type 2 diabetic rats decreased compared with the 6th week of intervention.And serum SOD levels were lower in the low-dose group and the rosiglitazone group than in the T2 DM group(P <0.05),but which still lower than the normal control group(P <0.05).At the 6th week of intervention,the serum MDA levels in the low-dose pterostilbene group,the middle-dose pterostilbene group and the rosiglitazone group were significantly lower than those in the T2 DM control group(P<0.05),and were higher than those in the control group(P< 0.05).At the 12 th week of intervention,the serum MDA levels in the low-dose pterostilbene group and the rosiglitazone group were lower than those in the T2 DM control group(P<0.05),and there was no significant difference from the control group(P>0.05).(6)The effect of the expression of PPAR? and PI3 K protein in adipose tissue: At the 6th week of intervention,the expression of PPAR? and PI3 K in adipose tissue of control group,low-dose pterostibene group,middle-dose pterostibene group,high-dose pterostilbene group,and rosiglitazone group were higher than that of T2 DM control group.At the 12 th week of intervention,compared with the control group,the levels of PPAR? protein in the T2 DM control group,the low-dose pterostilbene group,the middle-dose pterostilbene group,the high-dose pterostilbene group,and the rosiglitazone group were decreased(P <0.05).Compared with the T2 DM control group,the levels of PPAR? in the control group,the low-dose pterostilbene group,and the rosiglitazone group were decreased(P<0.05).The expression of PI3 K protein in adipose tissue of T2 DM control group rats and high-dose pterostilbene group were lower than that of control group,low-dose pterostilbene group,middle-dose pterostilbene group,and rosiglitazone group(P<0.05).These results indicate that pterostilbene intervention can promote the expression of PPAR? and PI3 K protein in adipose tissue of type 2 diabetic rats,and the effect of low dose is more obvious.Conclusion 1.The levels of blood glucose,serum lipids and serum insulin in type 2 diabetic rats were elevated;the levels of SOD in serum was decreased and the level of MDA in serum was increased.There was an obvious oxidative stress state;the expression of PPAR? and PI-3K protein in adipose tissue was reduced,which aggravated as the course of the disease progresses.2.Pterostilbene can improve the pathological changes of pancreatic tissue in type 2 diabetic rats and inhibit the formation of cytoplasmic vacuolation of islet ? cells.3.Pterostilbene can reduce fasting blood glucose,serum insulin and serum lipid levels in type 2 diabetic rats,and improve the suger and lipids metabolism of type 2 diabetic rats,increase the level of SOD in serum,reduce the level of MDA,increase the antioxidant capacity of type 2 diabetic rats,and the effect of low-dose pterostilbene is better,promote the expression of PPAR? and PI3 K protein in adipose tissue,improve glucolipid metabolism of type 2 diabetic rats by activating PPAR?,and the effect of low-dose pterostilbene is better. |
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