The Pathogenesis Of Gastrointestinal Dysfunction After Myocardial Infarction In Rats And Prevention And Treatment Of Tongxinluo

Part One: Foundation of gastrointestinal dysfunction model in myocardialinfarction ratsObjective:To investigate the characteristic changes of gastrointestinaldysfunction in myocardial infarction rats.Methods:Thirty-five healthy female Wistar rats were divided randomlyinto three groups.AMI group was assigned to underwent the operation of acutemyocardial infarction with ligation of the coronary artery.ECG were obtainedat pre-operation and post-operation. Cardiac function was used to evaluate theAMI model. HE staining was applied to detect heart and distal ileum tissue.Gastric retention rate and gastrointestinal transit rate were determined usingcarbon powder labeling method.Results:After4weeks, heart HE staining showed typical characteristicsof myocardial infarction. The left ventricular internal diameters of systole(LVIDs,mm) and diastole (LVIDd,mm) increased (6.65±0.37vs3.30±0.17,P=0.000;8.25±0.26vs6.50±0.14,P=0.000),interventricular septal thickness atend diastole(IVSD,mm) decreased (1.47±0.11vs2.26±0.07,P=0.000), leftventricular ejection fraction (LVEF,%) and fractional shortening (FS,%) werelower(19.85±1.55vs51.49±2.01,P=0.000;39.23±2.82vs81.44±1.77,P=0.000).The intestinal mucosa damaged, neutrophil aggregation;gastric retentionrate(%) and gastrointestinal transit(%) rate increased(73.42±4.73vs55.36±5.16,P=0.019;49.32±5.05vs35.37±3.99,P=0.01).Conclusion: After4weeks, in AMI rats, gastrointestinal functiondisorders was investigated, the intestinal mucosa damaged and gastrointestinalmotility disorders were presented,implying the success of gastrointestinaldysfunction model after myocardial infarction. Part Two: The pathogenesis of gastrointestinal dysfunction after myocardialinfarction in ratsObjective:Based on the intestinal microcirculation disorder-inflammatio-n-serotonin (5-HT) metabolic abnormalities, the pathogenesis of gastrointesti-nal dysfunction after myocardial infarction in rats was explored.Methods:Gastrointestinal dysfunction model with myocardial infarctionwas established as the method above. Laser speckle microscopy was to measu-re distal ileum mesenteric blood flow at the intraoperation and postoperation.Immunohistochemical staining was utilized to detect indoleamine2,3-dioxyg-enase expression(IDO)in distal ileum tissue. High-performance liquid chroma-tography with fluorescence and ultraviolet detection was applied for thedetermination of5-hydroxytryptamine(5-HT), its precursor tryptophan(Trp),and its metabolite5-hydroxyindoleacetic acid(5-HIAA) levels as well as thelevel of kynurenine(Kyn) and kynurenic acid(KynA) in serum and distalileum.Results:Four weeks after modeling, at intraoperation, distal ileummesenteric blood flow decreased sharply.After3days,1week,2weeks,4weeks, low perfusion persisted, mesenteric blood flow in control ratsrecovered to the preoperative levels within2h. After4weeks, mesentericblood flow were lower than control group (210.31±8.41vs233.40±7.82,P=0.047). The expression of IDO (OD) increased (506.93±41.75vs359.10±31.43, P=0.035).5-HT(ng/g) in the serum and distal ileum increased(2594.92±192.85vs1661.17±204.13,P=0.002;258.11±37.06vs121.66±19.18,P=0.004)and5-HIAA(ng/g) were significantly higher in the distalileum(709.35±57.76vs509.29±24.75,P=0.031). There was no significantdifference among the precursor and the other metabolites.Conclusion:The falling intestinal perfusion combined with increasedIDO expression led to the inflammatory response,resulting the metabolicabnormalities of5-HT.The response chain can be the pathogenesis ofgastrointestinal dysfunction after myocardial infarction in rats. Part Three: The effect and its mechanism of Tongxinluo for gastrointestinaldysfunction after myocardial infarctionObjective: To investigate the effects and its mechanism of Tongxinluo ongastrointestinal dysfunction after myocardial infarction in rats.Methods:60rats were randomly divided into Sham group (n=10),theother50rats was underwent the left descending coronary artery ligation and30surviving rats were randomly assigned to AMI model group,L-1MTgroup,Tongxinluo group (n=10). The L-1MT group were fed with L-1MT,0.8mg/d, and the Tongxinluo group were fed with Tongxinluo,0.16g/d. After4weeks,gastric retention rate and gastrointestinal transit rate weredetermined.High-performance liquid chromatography with fluorescence andultraviolet detection was applied for the determination of5-HT, its precursortrp, and its metabolite5-HIAA levels in the serum and gastric antrum,as wellas the level of Kyn and KynA.Results: For gastrointestinal dysfunction after myocardial infarction,thesurface of gastric mucosa was red and white, blood vessels hemorrhaged andmuscle layer thinned;gastric retention rate(%) and gastrointestinal transitrate(%)increased(72.97±4.83vs60.90±4.06,P=0.027;55.30±2.98vs39.70±4.57,P=0.003); the content of5–HT(ng/g)and the ratio of Kyn/Trp(%) in serumincreased(2941.58±238.25vs1959.23±112.03,P=0.015;7.25±0.44vs5.48±0.35,P=0.034);the content of5–HT(ng/g),Kyn(ng/g) and the ratio of Kyn/Trp(%)in gastric antrumin dcreased (3696.92±595.89vs2017.44±308.35,P=0.010;244.49±26.13vs153.46±18.82,P=0.008;2.68±0.26vs1.72±0.23,P=0.009).Afterapplication of L-1MT, gastric mucosal representation has no obviousimprovement, gastric retention rate(%) and gastrointestinal transit rate(%)decreased (56.17±1.63vs72.97±4.83,P=0.000;41.30±2.94vs55.30±2.98,P=0.012), the content of5–HT(ng/g) and the ratio of Kyn/Trp(%) in serumwere lower (2096.57±132.61vs2941.58±238.25,P=0.046;5.55±0.73vs7.25±0.44,P=0.016),the content of5–HT(ng/g)in gastric antrum decreased(2439.62±388.17vs3696.92±595.89,P=0.048).After application of Tongxinluo,gastric mucosal hyperemia and hemorrhage were improved. Gastric retention rate(%) and gastrointestinal transit rate (%) decreased (56.17±1.63vs72.97±4.83,P=0.003;42.39±3.12vs55.30±2.98,P=0.007).5-HT(ng/g)and ratioof Kyn/Trp(%) in serum decreased (2109.37±68.87vs2941.58±238.25,P=0.040;5.27±0.26vs7.25±0.44,P=0.009).The level of5-HT(ng/g), Kyn(ng/g)and ratio of Kyn/Trp(%)in gastric antrum decreased(2250.60±388.62vs3696.92±595.89,P=0.024;171.78±28.11vs244.49±26.13, P=0.031;1.77±0.30vs2.68±0.26,P=0.013). There was no significant difference among theprecursor and the other metabolites.Conclusion:The gastrointestinal motility can recover on the interventionof Tongxinluo,improving inflammation and correcting the distal5-HTmetabolic abnormalities.5-HT can be used as a new functional and therapeutictarget of gastrointestinal disorders for further research.