| BackgroundMetabolic syndrome (MS) is a general concept of clinical diseases characteristic of insulin resistance, which seriously threatens the human health. MS remarkably increases the morbid risk and mortality of diabetes as well as cardiovascular disease, therefore, it is significant to investigate the pathogenesy and block the onset pathway.The precondition of investigation is to establish an animal model which mimics MS.In the present time, there are several methods to establish a MS model: transmission, transgene, gene knock-out or medicine induction, environmental induction (diet induction) and so on, which merely equip with a part of features of metabolic syndrome, and have significant difference with the human metabolic syndrome .Experiments indicate that high-sucrose diet is associated with glycolipid metabolic disturbance and insulin resistance, and high-salt diet leads to hypertension. Moreover, high-sucrose diet can also activate RAAS.All these result in ventricular remodeling.Therefore, we intend to establish a MS model of Wistar rat combinedly fed with high-sucrose and high-sodium diet.In the meanwhile, we will explore whether there exists changes in left ventricular structure and function between MS model and normal control in the early stage.In recent years, massive experiments indicate that inflammatory reaction plays an important role in the generation and development of MS.In 2000, Festa concluded that chronic clinical inflammation is a critical step leading to insulin resistance and MS, moreover, the signaling pathway of inflammatory reaction has close relationship with insulin resistance.Right now, synthetic therapeutic approach for MS involves exercise , diet control, adjusting lipid, lowering saccharide and hypertension and so on .Since inflammation plays an important role in the process of MS, the anti-inflammatory therapy of MS attracts many people's attentions .Kon deemed that statins could not only lower lipid, but also inhibit inflammatory reaction.Kim found that aspirin can prevent and ameliorate the generation of insulin resistance in somatic muscles through inhibiting insulin signaling transduction and functional defection induced by obesity.Coptidis Decoction for Detoxification , a representative prescription of heat-clearing and detoxicating, is composed of coptis, cortex phellodendri, scutellaria and gardenia.Available evidence suggests that the prescription can decrease the expression of inflammatory factors,such as TNF-α , IL-1, IL-6, and ameliorate rat insulin resistance, which establish a solid foundation for the deep exploration of our research .So we propose that Coptidis Decoction for Detoxification can relieve insulin resistance and ameliorate MS by inhibiting inflammatory reaction as well as strengthening insulin receptor signaling transduction pathway. Aims1.To establish a MS model of rats fed with high-sucrose and high-sodium diet.2.To explore the changes of left ventricular structure and function in the rat MS model.3.To explore the influences of Coptidis Decoction for Detoxification and aspirin on MS. Methods1 .Animals72 Male Wistar rats at the age of 6 weeks old were randomly divided into 2 groups: MS model gruop(n=62) and normal control (n=10).After MS models being established ,34 rats of MS models were randomly divided into 3 groups, Coptidis Decoction for Detoxification group(3.5g/kg/d , n=11),aspirin group(120mg/kg/d, n=13) and distilled water group (n=10). Rats of normal control proceed to be fed with ordinary diet.2.Contents(1) The measument of diagnostic criteria on MS;(2) The measument of left ventricular structure and function; (3) The examination of heart ultramicrostructure and pathological. Results1.The condition of experimental animalsIn all, there were 45 qualified MS model, 3 died , 12 body weight disqualification and 2 blood glucose disqualification. 10 wistar rats were all qualified in wistar-control group.In the process of drug intervention, 1 rat died in aspirin group.2.The measument of diagnostic criteria on MS2.1 Body weightCompared with the 22-week-old ordinary diet group, MS model group, aspirin group, Coptidis Decoction for Detoxification group and distilled water group in the 22 weeks all showed remarkably increased body weight (all P<0.05-0.01).There was no statistical difference regarding body weights among intervention groups (P>0.05).2.2 Comparison of SBPCompared with that in the 10, 12, 14, 16, 18, 20 and 22-week-old normal control, the blood pressure in the same old MS model group was all increased remarkably (all P<0.05). Compared with that in the 22-week-old normal control, the blood pressure in the same old aspirin group, Coptidis Decoction for Detoxification group and distilled water group was all increased remarkably (all P<0.01). Compared with that in the 34-week-old distilled water group, the blood pressure in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group was all decreased remarkably (all P<0.01). Compared with that in the 34-week-old normal control, the blood pressure in the 34-week-old distilled water group, aspirin group and Coptidis Decoction for Detoxification group was all increased remarkably (all P<0.01).2.3 Comparison of fasting blood glucoseCompared with that in the 22-week-old normal control, the fasting blood glucose in the 22-week-old MS model group was increased remarkably(P<0.01).Compared with that in the 22-week-old normal control, the fasting blood glucose in the 22-week-old distilled water group, aspirin group and Coptidis Decoction for Detoxification group was all increased remarkably (all P<0.01). Compared with that in the 34-week-old distilled water group, the fasting blood glucose in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group was all decreased remarkably (all P<0.01). Compared with that in the 34-week-old normal control, the fasting blood glucose in the 34-week-old distilled water group was increased remarkably(P<0.01).2.4 Comparison of insulinCompared with that in the 22-week-old normal control, the insulin in the 22-week-old MS model group was increased remarkably(P<0.01).Compared with that in the 22-week-old normal control, the insulin in the 22-week-old aspirin group was increased remarkably(P<0.01).Compared with that in the 34 weeks old normal control, the insulin in the 34-week-old distilled water group was increased remarkably(P<0.01).2.5 Comparison of insulin resistance indexCompared with that in the 22-week-old normal control, insulin resistance index in the 22-week-old MS model group was increased significantly (P< 0.01).Compared with that in the 22-week-old normal control, insulin resistance index in the 22-week-old distilled water group , aspirin group and Coptidis Decoction for Detoxification group were all increased significantly (P <0.05-0.01). Compared with that in the 34-week-old distilled water group, insulin resistance index in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group were all decreased significantly (all P < 0.05-0.01). Compared with that in the 34-week-old Normal control, insulin resistance index in the 34-week-old distilled water group was increased significantly (P <0.01).2.6 Comparison of low density lipoprotein cholesterolCompared with that in the 22-week-old normal control, C-LDL in the 22-week-old MS model group was not changed significantly (P>0.05).Before drug intervention in the 22-week-old , there was no statistical difference in LDL comparison among Coptidis Decoction for Detoxification group, aspirin group, distilled water group and normal control.( all P>0.05).After drug intervention, there was still no statistical difference among interwention groups (P>0.05).2.7 Comparison of high density lipoprotein cholesterolCompared with that in the 22-week-old normal control, C-HDL in the 22-week-old MS model group was not changed significantly (P>0.05).Before drug intervention in the 22 week old , there was no statistical difference in HDL comparison among Coptidis Decoction for Detoxification group, aspirin group, distilled water group and normal control (all P>0.05).Compared with 34-week-old aspirin group,C-HDL in the 34-week-old Coptidis Decoction for Detoxification group was increased significantly(P<0.01).2.8 Comparison of total cholesterolCompared with that in the 22-week-old normal control, total cholesterol in the 22-week-old MS model group was increased significantly (P<0.05).Before drug intervention in the 22 week old , there were no statistical difference in total cholesterol comparison among Coptidis Decoction for Detoxification group, aspirin group, distilled water group and normal control (all P>0.05). After drug intervention, there was still no statistical difference among interwention groups (P>0.05).2.9 Comparison of triglycerideCompared with that in the 22-week-old normal control, TG in the 22-week-old MS model group was not changed significantly (P>0.05).Before drug intervention in the 22 week old , there was no statistical difference in TG comparison among Coptidis Decoction for Detoxification group, aspirin group, distilled water group and normal control(all P>0.05).After drug intervention, there was still no statistical difference among intervention groups (P>0.05).3.The measument of left ventricular structure and function3.1 Comparison of left ventricle end-diastolic diameterCompared with that in the 22-week-old normal control, left ventricle end-diastolic diameter in the 22-week-old MS model group was not changed significantly (P>0.05).Before drug intervention in the 22 week old , there was no statistical difference in left ventricle end-diastolic diameter comparison among intervention groups(all P>0.05).After drug intervention, there was still no statistical difference among intervention groups (all P>0.05). 3.2 Comparison of left ventricle end-systolic diameterCompared with that in the 22-week-old normal control, left ventricle end- systolic diameter in the 22-week-old MS model group was not changed significantly (P>0.05).Before drug intervention in the 22 week old , there was no statistical difference in left ventricle edn-systolic diameter comparison among intervention groups (all P>0.05).After drug intervention, there was still no statistical difference among intervention groups(all P>0.05).3.3 Comparison of interventricular septumCompared with that in the 22-week-old normal control, interventricular septum in the 22-week-old MS model group was increased significantly (P<0.01).Compared with that in the 22-week-old normal control, interventricular septum in the 22-week-old aspirin group, distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (all P < 0.05-0.01). Compared with that in the 34-week-old normal control, interventricular septum in the 34-week-old distilled water group was increased significantly (P<0.01). 3.4 Comparison of posterior left ventricleCompared with that in the 22-week-old normal control, posterior left ventricle in the 22-week-old MS model group was increased significantly (P < 0.01).Compared with that in the 22-week-old normal control, posterior left ventricle in the 22-week-old aspirin group , distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (all P < 0.05 -0.01). Compared with that in the 34-week-old normal control, posterior left ventricle in the 34-week-old distilled water group was increased significantly(P<0.01)3.5 Comparison of left ventricle weightCompared with that in the 22-week-old normal control, left ventricle weight in the 22-week-old MS model group was increased significantly (P < 0.01).Compared with that in the 22-week-old normal control, left ventricle weight in the 22-week-old aspirin group, distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (all P <0.05—0.01). Compared with that in the 34-week-old distilled water group, left ventricle weight in the 34-week-old aspirin group was decreased significantly (P < 0.05).Compared with that in the 34-week-old normal control, left ventricle weight in the 34-week-old distilled water group was increased significantly (P < 0.01).3.6 Comparison of E waveCompared with that in the 22-week-old normal control, E wave in the 22-week-old MS model group was decreased significantly (P < 0.01).Compared with that in the 22-week-old normal control, E wave in the 22-week-old aspirin group , distilled water group and Coptidis Decoction for Detoxification group were all decreased significantly (all P < 0.05-0.01). Compared with that in the 34-week-old distilled water group, E wave in the 34-week-old Coptidis Decoction for Detoxification group and aspirin were increased significantly (P < 0.05). Compared with that in the 34-week-old normal control, E wave in the 34-week-old distilled water group was decreased significantly (P < 0.01).3.7 Comparison of A waveCompared with that in the 22-week-old normal control, A wave in the 22-week-old MS model group was increased significantly (P < 0.01).Compared with that in the 22-week-old normal control, A wave in the 22-week-old aspirin group , distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (P < 0.05- 0.01). Compared with that in the 34-week-old normal control, A wave in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group were increased significantly (P < 0.01).3.8 Comparison of E/A ratioCompared with that in the 22-week-old normal control, E/A ratio in the 22-week-old MS model group was decreased significantly (P < 0.01).Compared with that in the 22-week-old normal control, E/A ratio in the 22-week-old aspirin group , distilled water group and Coptidis Decoction for Detoxification group were all decreased significantly (P < 0.05—0.01). Compared with that in the 34-week-old distilled water group, E/A ratio in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group were increased significantly (P < 0.05). Compared with that in the 34-week-old normal control, E/A ratio in the 34-week-old aspirin group , distilled water group and Coptidis Decoction for Detoxification group were all decreased significantly (all P < 0.01).3.9 Comparison of Tei index Compared with that in the 22-week-old normal control, Tei index in the 22-week-old MS model group was increased significantly (P<0.01).Compared with that in the 22-week-old normal control, Tei index in the 22-week-old aspirin group, distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (P < 0.05). Compared with that in the 34-week-old distilled water group, Tei index in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group were decreased significantly (P < 0.05-0.01). Compared with that in the 34-week-old normal control, Tei index in the 34-week-old aspirin group, distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (P <0.01).4. heart ultramicrostructure and pathological4.1 Comparison of myocardium collagen volume fractionThe myocytes was red or yellow and collagen was green or blue.The collagen tissue was appropriate arranged among cardiomyocytes in the normal control.However,collagen tissue increased makedly,and disrupted in some area in the distilled water group.The collagen tissue decreased and arranged regularly in the valsartan groups,compared with the distilled water group.Quantitative analysis results: Compared with that in the 34-week-old distilled water group,CVF in the 34-week-old Coptidis Decoction for Detoxification group and aspirin group were decreased significantly (P < 0.01). Compared with that in the 34-week-old normal control, CVF in the 34 weeks aspirin group, distilled water group and Coptidis Decoction for Detoxification group were all increased significantly (all P <0.05-0.01).4.2 Cardiomyocyte electron microscopy (HE stain)In normal control rats at 34 weeks, electron micrograph shows orderly aligned cardiomyocyte,homogenious nuclei,uniform staining endochylema and orderly arranged myofiber.Compared with distilled water group, cardiomyocytes decrease in quantity in aspirin group and Coptidis Decoction for Detoxification group at 34 weeks, accompanying cardiocyte hypertrophy,heterogeneous neclei,nonuniform staining endochylema,rarefied and deranged myofibers with disruption .The pathological changes of Coptidis Decoction for Detoxification group and aspirin group at 34 weeks are in the middle of the normal control and distilled water group. 4.3 The ultrastructural change of myocardium under electron microscopyIn distilled water group at 34 weeks , electron microscopy shows uneven cardiocyte surface ,disappearing nuclear membrane, decreasing pallid euchromatin, moreover, myocardium interstitial collagen increases and the endocytoplasmic reticulum of fibroblast swells.In this group, myofibers are aligned disoriented and sparsely, and disrupted in the middle.Meanwhile, the hyperplastic mitochondria overstock and autolyze , presenting pantomorphia with obscure Z-line.The normal cardiomyocyte nucleus was oval associated with clear nucleoli, intact nuclear membrane,clean myocardium interstitial substance, regular organized myofiber, evident sarcomere structure, intact mitochondria and clear Z-line.The pathological changes of Coptidis Decoction for Detoxification group and aspirin group are much slighter than distilled water group ,but more obvious than normal control group. Conclusion1 .Established metabolic syndrome rat model of obesity, hypertension, hyperinsulinemia and insulin resistance by feeding with high sugar-salt diet.2.The metabolism syndrome rat models appeared myocardial hypertrophy, diastolic dysfunction.3.After aspirin intervention, BP, fasting blood glucose and weight of MS model was lowered, and insulin resistance was effectively ameliorated.Myocardium hypertrophy and heart function were both improved by drug intervention ,meanwhile, myocardium microstructure and pathological changes were obviously ameliorated.4.After Coptidis Decoction for Detoxification intervention, BP, fasting blood glucose and weight of MS model was lowered, and insulin resistance was effectively ameliorated.Myocardium hypertrophy and heart function were both improved by drug intervention ,meanwhile, myocardium microstructure and pathological changes were obviously ameliorated.5.Compared with that in the Coptidis Decoction for Detoxification group,Cho in the Aspirin group was lowed significicantly. Compared with that in the Aspirin group,C-HDL in the Coptidis Decoction for Detoxification group was increased significantly. |
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