| PARTⅠStudy on the anti-inflammatory and antioxidant effect of L-carnitine in atherosclerotic ratsObjective:Atherosclerosis is the primary reason for the occurrence of cardiovascular disease and development, seeking to reduce atherosclerosis of the modulator is very important. The purpose of this study is to evaluate L-carnitine(acetyl-L-carnitine, ALCAR) in Wistar rats in the regulation of improving the ability of atherosclerosis, as well we have a deeper research on the mechanism of anti atherosclerosis effect of L-carnitine.Methods:Tirty-two Wistar rats were divided into four groups randomly:normal diet group (control group), normal diet+ALCAR group (ALCAR group), atherosclerosis group (AS group), atherosclerosis+ALCAR group (AS+ALCAR group). Atherosclerosis model using high fat feed+intramuscular injections of vitamin D3+ artery balloon injury in surgery to be built. ALCAR group and AS+ALCAR group were given the regular diet or high fat diet and were given L-carnitine 200 mg/kg/d.16 weeks later, the rats were killed, took a blood sample, the heart and aorta tissue as the target of research. We detected serum lipid distribution, oxidative stress, inflammatory factors and adiponectin levels. HE staining were used to observe aortic pathology structure; We also detected the aortic and heart tissue oxidation and aortic content of angiotensin Ⅱ. QPCR method to detect aortic tissue and heart tissue’s iNOS, IL-ip and TNF-a’s mRNA expression; Western blot method to detect the aortic and heart tissue’s iNOS, IL-1β, TNF-a and CRP protein expression. Statistical tests using SPSS 17.0 software, the difference between groups using analysis of variance (ANOVA), the difference between two groups using the minimum significant difference (LSD) for detection, If the variance is not homogeneous, use the Dunnett’s T3 test. If it is non-normal distribution, using Mann-Whitney test. value of P<0.05 has statistical significance.Results:1. ALCAR regulates serum lipid profiles. Compared with control group, AS group serum TC, TG, LDL-C and VLDL-C content increases significantly, HDL-C levels decreased significantly (P<0.01). Compared with the AS group, AS+ALCAR group rats serum TC, TG, LDL-C and VLDL-C content decreased significantly, HDL-C levels significantly increased (P<0.01). Normal diet after giving ALCAR, compared with normal group, the serum TC, TG, LDL-C and VLDL-C content has a certain decline, but there was no significant statistical difference (P>0.05), HDL-C levels was significantly elevated (P<0.05).2. ALCAR attenuated the oxidative stress. In atherosclertic rats, the activities of SOD and GSH-Px in serum and aorta tissue were weaker than those in normal control group while the levels of MDA were higher(P<0.01 or P<0.05). ALCAR could enhance the SOD and GSH-Px activities and decline the MDA levels (P<0.05).3. ALCAR down-regulated the expressions of inflammnation factors in serum. The concentrations of TNF-α、IL-1β and CRP in serum were siginificantly increased in atherosclerotic rats(P<0.01). ALCAR could decrease the concentrations of TNF-α、 IL-1β and CRP(P<0.01 or P<0.05). However, ALCAR had no effects on adiponectin (O>0.05).4. The control group, the rats in group ALCAR of the aorta vascular lumen is large, thin wall, intimal structure clear and smooth, the internal elastic membrane integrity, smooth muscle cells arranged regularly, and the internal elastic membrane in parallel. Narrow lumen of atherosclerotic rats, wall thickening, endothelial cell loss, endothelial gap widened, internal elastic membrane rupture and a wave shaped, the middle elastic membrane, and smooth muscle cells arranged in disorder, some smooth muscle cells proliferation, plaque shows a large number of foam cells and lipid deposition. The lumen area of the AS+ALCAR group was significantly larger than that of the AS group, and the severity of the plaque was far lower than that of the AS group.5. ALCAR reduced the concentrations of angiotensin II in aorta.The concentration of angiotensin Ⅱ was significantly increased in AS rats. (P<0.01) ALCAR could significantly reverse the high expressions of angiotensin II in aorta induced by atherosclerosis (P<0.05).6. ALCAR regulates the gene expression of inflammatory markers in aorta tissue. Real-time quantitative PCR analysis of inflammatory markers showed that ALCAR significantly decreased the mRNA levels of CRP, TNF-a, iNOS, and IL-1β genes in aorta tissue. However, AS rats showed increased mRNA levels of inflammatory markers. These results might be a key evidence to speculate the mechanism of action of ALCAR against lipid deposition in aorta tissue.7. ALCAR down-regulated the levels of inflammatory factor in aorta.Western blot analysis showed that the protein expressions of TNF-a, IL-1β, iNOS and CRP in aorta tissue were significantly increased in AS rats. ALCAR could significantly decrease the protein expressions of TNF-a, IL-1β, iNOS and CRP in AS rats..8. ALCAR regulates the gene expression of inflammatory markers in heart tissue. Real-time quantitative PCR analysis of inflammatory markers showed that ALCAR significantly decreased the mRNA levels of CRP, TNF-a, iNOS, and IL-1β genes in heart tissue. However, AS rats showed increased mRNA levels of inflammatory markers. These results might be a key evidence to speculate the mechanism of action of ALCAR against lipid deposition in heart tissue.9. ALCAR down-regulated the levels of inflammatory factor in heart.Western blot analysis showed that the protein expressions of TNF-a, IL-1β, iNOS and CRP in heart were significantly increased in AS rats. ALCAR could both significantly decrease the protein expressions of TNF-a, IL-1β, iNOS and CRP in AS or normal rats..Conclusion:ALCAR can inhibit the development of atherosclerosis by regulating blood lipid, inhibiting the expression of inflammatory factor gene and antioxidation. ALCAR can reduce the expression of genes and proteins in the heart tissue of AS rats, which may be related to the protection of anti-coronary artery atherosclerosis and myocardial protection. The follow-up needs to carry out a more in-depth study of the mechanism.PARTⅡThe role of L-carnitine for patients with unstable angina clinical efficacy of anti-inflammatory and anti-oxidantObjective:To observe the clinical therapeutic effect of L-carnitine on patients with coronary heart disease unstable angina and its antioxidant and anti-inflammatory effects and further explore the mechanism of L-carnitine in treatment of coronary heart disease.Methods:115 cases of patients with chest pain or chest tightness in the Department of internal medicine of Weifang People’s Hospital from August 2012 to December 2013, Diagnosis of unstable angina pectoris, were randomly divided to two groups, control group (n=55) was treated with conventional drugs to treat coronary heart disease, treatment group (n=60) in the basis of routine treatment, L-carnitine (2g/d) in intravenous injection way for 7 days instead of daily oral 2g to 56 days. The clinical symptoms, blood lipid were observed and we measured GSH-Px, MDA, CRP, IL-6, TNF-a level to evaluate the role of L-carnitine anti-inflammatory and antioxidant. Application SPSS 17.0 statistical software, the data from this study were statistically analyzed, two groups of sample mean were compared using independent samples t-test, count data using the chi-square test. The statistical analysis results indicated that there were significant differences by P<0.05.Results:1. There are two cases in the control group, the treatment group three cases due to loss of follow-up, withdraw from the trial, during follow-up did not occur adverse drug reactions.After treatment, the total effective rate of the treatment group was 91.22% and the control group 84.91% and it was not statistically significant, but the efficiency of the treatment group 47.37% was significantly higher than the control group 24.53%, the difference was statistically significant (P<0.05).2. The levels of TC, LDL-C, TG and HDL-C were not significantly different in the two groups before treatment. After treatment, the levels of LDL-C and TG in the control group were significantly lower than those before treatment (P<0.01), and the level of HDL-C was not significantly changed (P>0.05). Compared with the previous treatment, TG and LDL-C levels in the treatment group significantly decreased (P <0.01), and HDL-C levels rise (P<0.05), after treatment, the treatment group compared with the control group, TG levels more significantly reduced (P<0.01), HDL-C levels significantly higher than the control group (P=0.01). Compared with the control group, TC, LDL-C was no significant difference (P=0.11).3. Two groups before treatment GSH-Px, MDA did not show significant difference (P>0.05), the two groups after treatment than before treatment GSH-Px were significantly increased, MDA decreased significantly (P<0.01), after treatment, the treatment group compared with the control group GSH-Px increased, MDA decreased significantly (P<0.01, P<0.05).4. Two groups before treatment hs-CRP, IL-6, TNF-a did not show significant difference (P>0.05), the two groups after treatment hs-CRP, IL-6, TNF-' significantly decreased (P<0.01), the treatment group than the control group after treatment decreased more obviously (P<0.01,P<0.05), it was statistically significant.Conclusion:L-carnitine to improve the symptoms of coronary heart disease unstable angina have exact curative effect, and can regulate blood lipids profile, improve the antioxidant enzymes activity, reduce lipid peroxidation, reduce inflammation, treatment of atherosclerosis, to treat coronary heart disease. |
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