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Relation among Remodling of Intesititum, Sympathetic Nerve and PCK Activation in Heart Failure Rats Induced by Long-term Cardiac Pressure Overload

Author: HuBing
Tutor: LiHe
School: Hebei Medical University
Course: Internal Medicine
Keywords: Cardiac pressure overload heart failure sympathetic nervedensity norepinephrine transporter protein myocardial interstitial PKC ε
CLC: R541.6
Type: Master's thesis
Year: 2014
Downloads: 4
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Abstract

Objective：This work aimed to observe the effects of protein kinase Cactivation involved in heart failure quality and sympathetic remodeling inmyocardial pressure overload rat. The relation between cardiac sympatheticremodeling and myocardial interstitial, as well as sympathetic andredistribution of membrane protein changes were studied to determine the roleof protein kinase C epsilon activation on remodeling of cardiac sympatheticand myocardial interstitial.Methods：Thirty male Wistar rats aged7weeks were randomly dividedinto two groups: sham group (SHAM)(n=15) and the pressure load modelgroup (POL)(n=15). Before surgery, POL group rats were weighed andanaesthetized with1%sodium pentobarbital in40mg/Kg weight dosage.Cuttinga longitudinal incision was made in the abdomen at the midline slightlyleft0.5cm to expose the surgical field. The right renal artery to the aorticbifurcation at0.5cm were freed to the aortic sheath, and the8th needle(diameter of about0.8mm) was placed parallel to artery, then the needle wasligated with a3-0surgical thread ligation together with the aorta. The needlewas withdrawn after ligation was made, causing about50%stenosis. Penicillinof200,000units was injected in the abdominal cavity after3consecutive daysto prevent infection. SHAM rats received the same operation exception ofaortic ligation, only with the line linked on. Eight weeks after surgery, rat wasweighed and anesthetized again, and a micro-catheter was inserted andgradually retrograded to the left ventricle via the carotid artery. Cardiaccatheter tip pressure transducer was connected through a biological medicalrecords system using silk thread Cath fixed in the blood vessels to monitor theleft ventricular systolic pressure, the left ventricular end-diastolic pressure, the max maximal rate of rise of left ventricular pressure and the max maximal rateof decline of left ventricular pressure (dp/dtmax) with ventricular invasivehemodynamic detection method. After detection of invasive hemodynamicparameter, Rats received intracardiac injection with10%potassium chloridesolution in1ml and were sacrificed using thoracotomy to remove the heart.The organs were washed with saline and were separated into the left, rightventricle, and the atria and great vessels were cut on dry filter paper. Leftventricle mass were weighed, fast freeze in liquid nitrogen and stored at-80°C refrigerator. Left ventricular collagen tissue changes were observedusing polarized light microscopy. Tyrosine hydroxylase (tyrosine hydroxylase,TH) and neonatal neurological markers-growth associated protein (GrowthAssociated Protein43, GAP43) expression were detected withimmunohistochemistry. Myocardial cell membrane and norepinephrinetransporter (Norepinephrine transporter, NET) and protein kinase C ε (Proteinkinase C epsilon, PKC epsilon) expression in the cytoplasm were analyzedusing the Western Blot. Data were analyzed by image analysis system (ImagePro Plus6.0). Experimental data were used using SPSS13.0software, and P<0.05was considered statistically significant.Results：1Invasive hemodynamic: Left ventricular end-diastolic pressure(LVDEP) increased (P＜0.05) compared with sham group. Left ventricularsystolic pressure, the maximum rate of change of left ventricular pressure (±dp/dtmax) were lower (P＜0.05)(LVSP) than that of POL group.2The ratio of the heart weight and body weight (HW/BW) of POL groupincreased in1.34folds compared with that of SHAM group (P＜0.05). Theresults show that POL group had cardiac hypertrophy.3The ratio of the plasma norepinephrine concentration of POL groupsignificant increased compared with that of SHAM group (P＜0.05) usingradioimmunoassay determination.4High power microscope observations show that the length and thediameter of myocardial cells of POL group increased compared with the SHAM group (P＜0.05).5Myocardial collagen I and interstitial and perivascular III type wereincreased compared with that of SHAM group determined using Sirius redstaining and polarizing microscope. Image analysis showed that collagenvolume ratio (ICVF) of POL group increased by1.69-folds (P＜0.05)compared with that of the SHAM group.6Compared with SHAM group, myocardial TH protein and myocardialGAP43protein expression of POL group increased significantly (P＜0.05)using immunohistochemical assay.7Compared with the SHAM group, ratio of net myocardial cellmembrane and cytoplasm protein and PKC epsilon protein ratio values of POLgroup increased significantly(P＜0.05) by Western Blot.Conclusions：1POL could lead to cardiac hypertrophy, myocardial collagen precipitateendoplasmic abnormal increase in heart increased, decreased heart function,and finally the development of heart failure;2PKC epsilon protein activation induced POL promotes collagensecretion and the NET internalization. Long-term POL induce myocardialfibrosis and sympathetic remodeling, and PKC epsilon protein activation mayplay an important intermediary role in these changes.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Blood circulation failure
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