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1.Protective Effects Of Lithium On Neonatal Rats Cardiomyocytes Exposed To High Glucose 2.Effect Of Sinvastatin On Cardiomyocyte Apoptosis Induced By Endoplasmic Reticulum Stress In Rats With Hyperlipidemia

Posted on:2011-07-28Degree:MasterType:Thesis
Country:ChinaCandidate:B ZhangFull Text:PDF
GTID:2154360308984549Subject:Geriatrics
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Objective:To investigate the effects of different concentrations of lithium(LiCl) on neonatal rat cardiomyocytes exposed to high glucose, and study the protective effects of canonical Wnt signaling pathway on cardiomyocytes.Methods:The ventricular myocardium of neonate rats about 1-3 day old was obtained. Then, the primary culture cardiomyocytes were randomly divided into 4 groups: control group, high glucose damaged group, LiCl 5 mmol·L-1 group and LiCl 10 mmol·L-1 group. The morphological of cardiomyocytes were observed by inverted microscope, the apoptotic cardiomyocytes were tested by terminal deoxynucleotidyl transferase mediated dUTPbiotin nick end labeling(TUNEL), the protein experssions of p-GSK-3βandβ-catenin was detect with immunocytochemistry staining. Result: Compared with high glucose damaged group, pulsation freguency of cardiomyocyte tended towards nomal, the apoptotic cardiomyocytes were decreased(P<0.05), the expressions of p-GSK-3β andβ-catenin were increased(all P<0.05)in LiCl 5 mmol·L-1 group and LiCl 10 mmol·L-1 group.Conclusion: LiCl can significantly inhibit the injury of cardiomyocytes induced by high glucose, its mechanism may be related to the activation of canonical Wnt signaling pathway. Objective:To investigate the cardioprotection and its mechanism of simvastatin on cardiomyocyte apoptosis induced by endoplasmic reticulum stress in rats with hyperlipidemia.Methods:Twenty-four male Wistar rats were randomly divided into three groups: normal control group(n=8, fed with normal diet), high fat group(n=8, fed with high fat diet) and simvastatin group(n=8 , fed with high fat diet and received simvastatin 10mg·kg-1d-1 by gastric irrigation). After twelve weaks, the serum triglycerides(TG) and total cholesterol(TC) levels were determined by completely automatic biochemistry meter. The pathological changes of myocardial tissue were detected by HE staining. The apoptotic cardiomyocytes of myocardial tissue were tested by terminal deoxynucleotidyl transferase mediated dUTPbiotin nick end labeling(TUNEL). The expression of endoplasmic reticulum stress(ERS) associated molecle-glucose regulated protein(GRP)78 in myocardial tissue was investigated by immunohistochemistry and RT-PCR.Results:Compared with normal control group, the serum TG and TC levels, and the numbers of apoptotic cardiomyocytes as well as the expression of GRP78 protein and GRP78 mRNA in myocardial tissue were significantly increased in high fat group (P<0.01 or 0.05). Compared with the high fat group, the serum TG and TC levels, and the numbers of apoptotic cardiomyocytes as well as the expression of GRP78 protein and GRP78 mRNA in myocardial tissue were remarkably reduced in simvastatin group but still higher than those in normal control group (all P<0.05).Conclusions:The hyperlipidemia can induce myocardiocyte apoptosis through activating ERS signaling pathways. The simvastatin can inhibit the myocardocyet apoptosis induced by hyperlipidemia through amelioration of ERS.
Keywords/Search Tags:lithium, glycogen synthase kinase-3beta, β-catenin, Wnt signaling pathway, cardiomyocyte, Rat, Hyperlipidemia, Endoplasmic reticulum stress, Cardiomycyte apoptosis, Simvastatin
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