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Effect And Significance Of Simvastatin On Plasma Endothelial Lipase In The Atherosclerotic Rats

Posted on:2013-12-04Degree:MasterType:Thesis
Country:ChinaCandidate:Z J GuoFull Text:PDF
GTID:2234330374452315Subject:Geriatrics
Abstract/Summary:PDF Full Text Request
Background&objectiveThis project intended to study the plasma endothelial lipase (EL) level ofatherosclerotic lesions in rats. Explored the impact of EL change after Simvastatintreatment, and analyzed EL correlation with CRP, HDL-C, plaque diameter, lumen size.Then explored the role of EL in atherosclerosis and the role of anti-atherosclerosis aftersimvastatin influenced the EL level. EL inhibitors reducing inflammation, increasingHDL-C levels may provide a new strategy for the treatment of arterial atheroscleroticcardiovascular disease.We look forward into bring the gospel to the atherosclerosis patientswith the diagnosis, treatment and prognosis.Research methodsFirst Build rats model of atherosclerosis30SD rats were randomly divided intothree groups, each group was10rats, control group was given normal diet.Atherosclerosisgroup and simvastain group (collectivelly known as the model group) were given high fatfeeding, and given Bovine serum albumin plus ovalbumin vascular immune stimulationplus large doses of vitamin D3orally plus high fat feeding to build the model.Second Detected three groups of rat lipid levels, C-reactive protein (CRP) andplasma EL levels at the end of fed1d,6w,12w and checked carotid artery ultrasound at theend of fed6w and12w. Then evaluated atherosclerosis model whether was successful, andunsuccessful rats were removed.Third The succeed model rats continued high fat diet, the simvastatin group ratswere gavaged with simvastatin (2.5mg/kg.d) dissolved in1ml normal saline, and the rest ofthe group given the same amount of normal saline intragastrically eight weeks.Forth Checked the model rats carotid artery ultrasound at the end of feeding16wand20w, and obtained lumen diameter and plaque size after software analysis.Anddetected the TC, TG, HDL-C, LDL-C, CRP levels and EL levels in three groups of rats atthe end of feeding16w and20w. Rats were sacrificed and observed pathological changesby carotid HE staining at the end of20w.Fifth Analyzed EL correlation with CRP, HDL-C, plaque diameter, lumen size atthe model rats.Sixth Statistical approach: The data were expressed as mean±standard deviationamong groups were compared using single factor analysis of variance, homogeneity of variance with SNK method; heterogeneity of variance using Dunnett’s method. Thecorrelation between the two indicators was analyzed using Pearson correlation analysis.The data were analyzed using SPSS18.0statistical software, P<0.05was consideredstatistically significantResultFirst builded Atherosclerosis rat model After high-fat feeding6w and12w, themodel group compared with the model first day.TG, TC, LDL-C, CRP, EL weresignificantly higher (P<0.01), HDL-C decreased (P<0.05). The blood lipid levels, CRP andEL levels no significant difference between the high fat diet6w and12w. Vascularultrasound no obvious like atherosclerosis change in6week.But vascular ultrasound in12week show: atherosclerotic group and simvastatin group compared with healthy controlgroup carotid intima were significantly thicker, the surface is not smooth, discontinuity,showing non-uniform low-echo area. Showing that small plaques is prominent within thelumen, luminal partial formation of small narrow,blood vessels of the membrane and theouter membrane and its surrounding connective tissue boundaries is unclear. Prompted therats were succeed to model in12w.Second Three groups of rats fed for20weeks, blood lipids, CRP, EL fed for20weeks,detected the lipids, CRP, EL of the three groups, the results show,(1) Theatherosclerosis group compared with the healthy control group: blood TC, TG, LDL-C,CRP levels,EL levels were significantly increased (P<0.01), while HDL-C levels werelower (P<0.05).(2)The simvastatin group compared with atherosclerosis group: TC, TG,LDL-C, CRP levels, EL levels were significantly lower (P<0.01), while HDL-C levelswere increased (P <0.05).(3) Simvastatin group compared with the healthy control group:the blood of the TG level was significantly increased (P <0.01), while plasma TC, LDL-C,HDL-C, CRP, EL levels no significantchanges (P>0.05).Third At the end of12w,16w,20w of simvastatin group showed:(1)16w comparedwith12w, TC, TG, LDL-C, EL were significantly lower(P<0.01), although CRP wasreduced, but not statistically significant(P>0.05), although HDL-C was increased, but notstatistically significant (P>0.05).(2)20w compared with16w, TC, LDL-C, CRP, EL weresignificantly lower (P<0.01), although CRP was reduced, but not statistically significant(P>0.05), while TG, HDL-C no significant change (P>0.05).(3)20w compared with12w,TC, TG, LDL-C, CRP, EL were significantly lower(P<0.01), lthough HDL-C was increased,but not statistically significant (P>0.05). Forth EL correlation analysis with plasma HDL-C, CRP and plaque diameter andlumen diameter found that the EL associated with HDL-C level was negatively correlated,with CRP was positively correlated, with plaque area was positively,associated withlumen diameter was a significant negative correlation.Fifth Carotid ultrasound showed that the plaque area (mm2) was:2.01±0.03,1.66±0.06,1.13±0.03at the end of12w,16w,20w in the simvastatin group.there werestatistically significant (P <0.05). The luminal diameter (mm) was:0.65±0.03,0.75±0.03,0.92±0.03at the end of12w,16w,20w in the simvastatin group.there were statisticallysignificant (P<0.05).Sixth HE staining of the carotid artery. At the end of20w, the rats of control groupvascular intimal smooth, complete, good continuity. While carotid artery HE staining ofatherosclerosis group and the simvastatin group rats were atherosclerotic changes. HEstaining of the carotid arteries in the simvastatin group showed atherosclerotic lesions weresignificantly alleviate than atherosclerosis group.ConclusionFirst This study established atherosclerosis rats model by the stimulation of theimmune bovine serum albumin (BSA)+intraperitoneal injection of ovalbumin+high fatdiet+intragastric administration of large doses of vitamin D3. The result confirmed thatthe modeling method was successful.Second In atherosclerosis rat plasma EL, CRP level was increased, plasma HDL-Cconcentration was reduced, carotid artery plaque area was increased and lumen diameterwas narrowed, correlation analysis found that EL was positively correlated with CRP,plaque area, was negatively correlated with HDL-C and lumen diameter. Chronicinflammation leads to the EL increased, thereby increased the atherosclerotic lesions.Third After simvastatin treatment, the CRP, EL levels were significantly reduced,while HDL-C levels were increased, and plaque size reduction, lumen diameter increased,which possible reduced chronic inflammation, and decreased plasma EL concentrations,thereby increasing the concentration of HDL-C to partly reduce the role of atherosclerosis...
Keywords/Search Tags:artery atherosclerosis, endothelial lipase, simvastatin, inflammation, high-density lipoprotein
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