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Preparation And Evaluation Of A Rat Model Of Hyperlipidemia Combined With Hyperglycemia And Myocardial Infarction Combined With Disease And Syndrome

Posted on:2021-05-08Degree:MasterType:Thesis
Country:ChinaCandidate:Z Y WangFull Text:PDF
GTID:2434330632455857Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
PurposeCombined with the high-fat diet,intraperitoneal injection of STZ and left coron ary artery ligation and other modeling methods to prepare hyperlipidemia combined with hyperglycemia combined with myocardial infarction rat model,the macroscopic characterization information of the model rats was dynamically collected at different time points after myocardial infarction Under the guidance of the combination of dis ease and syndrome theory,its syndrome attributes are determined,and the dynamic evolution of syndromes is initially explained.At the same time,the physical and ch emical indicators of each group of model rats are detected at multiple time points,and the syndromes and biological indicators are analyzed and discussed.Correlation between disease and syndrome.Method1.200 male SD rats of 7-8 weeks old(body weight around 260-280g)were randomly divided into 5 groups,namely:sham operation group,simple myocardial infarction group,high fat myocardial infarction group,high glucose myocardial infarction group And high-fat high-sugar myocardial infarction group.After 3 days of adaptive feeding,the rats in the high-fat myocardial infarction group and the high-fat high-sugar myocardial infarction group were fed with high-fat feed,and the other groups were fed with normal feed.After 4 weeks,the hyperglycemic state model was established by intraperitoneal injection of STZ(streptozotocin)in the high glucose myocardial infarction group and the high fat high glucose myocardial infarction group.After continuing feeding for 1 week,the left anterior descending coronary artery was ligated in the simple myocardial infarction group,high fat myocardial infarction group,high glucose myocardial infarction group,and high fat high glucose myocardial infarction group,and the left anterior descending coronary artery was threaded and ligated after thoracotomy In order to establish a model of myocardial infarction,the sham operation group only threaded without ligation,and the animals in each group were kept on the original feed until the end of the experiment.The animals in each group were randomly divided into 3 batches at three time points on the 7th,14th,and 28th days after surgery,and the body weight,blood lipids,and blood glucose of each group of animals were dynamically monitored.2.Determine the success of the hyperlipidemia model by detecting the changes in blood lipid-related indicators(TC,TG,LDL-C,HDL-C)of each group of rats fed high-fat diet;7 days after intraperitoneal injection of STZ,blood collection method by tail tip The fasting blood glucose of the model rats was detected,and those with FBG≥16.7 mmol/L judged that the hyperglycemic model was successful;3 days after myocardial infarction,the changes in the ECG signal of the model rats were detected by a twelve-lead electrocardiograph.There are 6-8 pathological Q waves in the joint to indicate the success of myocardial infarction modeling.The behavioral indexes and macroscopic characterization of rats were observed at 3 time points of 7th,14th and 28th day after myocardial infarction,and dynamic monitoring of rat activity,sensitivity,bunching,tongue color,tongue body,tongue Characterization,quality of the tongue,auricle morphology,claw temperature,claw moisturization,fecal stool,lip color,claw nail morphology,etc.,and characterization of rats.Observe the respiration frequency of the stress state,tongue and foot color saturation,grip And other behavioral indicators,and judge the syndrome attributes of rats.3.Detection of serum myocardial enzymes(AST,LDH,CK,CKMB),blood lipids(TC,TG,HDL-C,LDL-C)at three time points on the 7th,14th and 28th day after operation),Inflammatory factors(IL-6,IL-1β,TNF-α),oxidative stress(MDA,NO,ox-LDL),neurohormones(AngⅡ,ET,ALD,BNP,NT-proBNP)and other related biology The level of the indicator changes.Pearson correlation analysis or Spearman rank correlation analysis was used to explore the correlation between biological indicators and syndrome evaluation elements.Result1.After 4 weeks of high-fat diet,the levels of TC,TG and LDL-C in the serum of rats with high-fat myocardial infarction group and high-fat high-glucose myocardial infarction group were significantly higher than those in sham operation group,simple myocardial infarction group and high-sugar myocardial infarction group(P<0.01),HDL-C level was significantly lower than sham operation group,simple myocardial infarction group and high glucose myocardial infarction group(P<0.05);STZ induced high glucose myocardial infarction group and high fat high glucose myocardial infarction group Fasting blood glucose was significantly increased in rats,and the fasting blood glucose value FBG≥16.7mmol/L was detected 7 days after injection of STZ;three days after ligation of the anterior descending coronary artery,electrocardiogram monitoring was performed on rats in each myocardial infarction group,and 12-lead ECG showed There were 6-8 pathological Q waves in rats of each myocardial infarction group.It is suggested that the models of simple myocardial infarction group,high fat myocardial infarction group,high glucose myocardial infarction group and high fat high glucose myocardial infarction group were successfully modeled.2.In the simple myocardial infarction group,the tongue r-value decreased,the b-value increased,and the APTT shortened at 7 days after the operation,which was judged as a blood stasis syndrome.The 14-28 days after the operation showed a decrease in grasping power,decreased mobility,and accelerated respiratory frequency The indications related to the Qi deficiency syndrome were determined as Qi deficiency and blood stasis syndrome.The high-fat myocardial infarction group was always judged as Qi deficiency and blood stasis syndrome from 7 days to 28 days after operation.The syndrome indications of blood stasis syndrome have always changed throughout the high glucose myocardial infarction group and the high fat high glucose myocardial infarction group after myocardial infarction,and the two groups of model rats also have dry paw skin desquamation,Tongue red shaojin and other symptoms of Yin deficiency syndrome.However,the high glucose and high glucose myocardial infarction groups had significant differences in the syndrome time window.The high fat and high glucose myocardial infarction group developed claw temperature on the basis of the relevant symptoms of Yin deficiency syndrome 7 days after surgery.Heat images with high sensitivity,high sensitivity,and increased activity were judged as yin-deficiency heat and blood stasis syndrome.From 14 days to 28 days after operation,they were judged as qi-yin deficiency and blood stasis syndrome;No heat phenomenon appeared in the last 7 days,and accompanied by changes in activity level,decreased grip,and decreased claw temperature.From 14 days to 28 days after surgery,it was always determined as a syndrome of deficiency of qi and yin and blood stasis.3.Compared with the simple myocardial infarction group,the oxidative stress injury in the high-fat myocardial infarction group continued to increase from 7 days to 28 days after surgery,mainly manifested in the continued significant increase of ox-LDL(P<0.01 or P<0.05);The reaction started from 14 days to 28 days after the operation mainly showed a significant increase in IL-6 and TNF-α(P<0.01);myocardial injury was the heaviest at 14 days after the operation,and showed a significant increase in CKMB and AngⅡ High(P<0.01 or P<0.05).Inflammatory reaction in the group with high glucose myocardial infarction was significantly aggravated from 7 days to 28 days after surgery,manifested as a significant increase in IL-6,IL-1β,and TNF-α(P<0.01);oxidative damage from 14 days after surgery Significantly began to worsen,manifested as a significant increase in MDA and ox-LDL at 14 and 28 days after surgery(P<0.05);myocardial injury was the most serious at 28 days after surgery,with AST,CK,CKMB,AngⅡ,BNP,NT-Significantly increased proBNP(P<0.05 or P<0.01).Oxidative stress injury and inflammation in the high-fat and high-glucose MI group were significantly aggravated from 7 to 28 days after surgery,manifested by a continuous and significant increase in IL-6,IL-1β,TNF-α,MDA,and ox-LDL High(P<0.05 or P<0.01);myocardial injury was significantly aggravated at 14 and 28 days after surgery,manifested as a continuous increase in AST,LDH,CK,CKMB,ALD,BNP,NT-proBNP(P<0.05 or P<0.01).Correlation analysis screened out 19 blood indexes,of which 13,16,and 8 indexes were involved in the formation of qi deficiency syndrome,blood stasis syndrome,yin deficiency heat syndrome/qi yin deficiency syndrome,and the relationship between indicators and syndrome Crossover,there are cases where the same indicator participates in the formation of multiple syndromes.Conclusion1.After superimposing different risk factors on the rat model of myocardial infarction,the syndrome properties and syndrome evolution characteristics of the model animals in each group showed obvious differences:the rats in the simple myocardial infarction group belonged to the blood stasis syndrome at 7 days after surgery,and from 14 days to 28 after surgery The day belongs to the syndrome of qi deficiency and blood stasis;the rats in the high-fat myocardial infarction group showed qi deficiency and blood stasis syndrome at three time points;28 days is the blood stasis syndrome of both qi and yin deficiency;the myocardial infarction group with high fat and high glucose shows the blood stasis syndrome of both qi and yin deficiency on days 7,14,28 after operation.It is suggested that risk factors such as hyperlipidemia and hyperglycemia,like myocardial ischemia,play an important role in the development of syndromes.2.In the change of biological indicators,each model group showed different degrees of damage in oxidative stress,inflammatory response,myocardial damage and so on.Correlation analysis results suggest that 13,16,8 biological indicators are involved in the formation of qi deficiency syndrome,blood stasis syndrome,yin deficiency heat syndrome/qi yin deficiency syndrome,and the biological indicators and syndrome cross each other.
Keywords/Search Tags:combined animal models with disease and syndrome, myocardial infar ction, qi deficiency and blood stasis, qi and yin deficiency, yin deficiency and internal heat
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