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Objective To evaluate the effect of atorvastatin preconditioning on cognitive function in isoflurane-anaesthetized mice.Methods Forty-eight healthy male C57BL/6 mice,aged 3 months,weighing 27-41 g,were divided into 3 groups (n =16 each) using a random number table:control group (group C),isoflurane anesthesia group (group Ⅰ) and atorvastatin preconditioning plus isoflurane anesthesia group (group AI).Atorvastatin 10 mg/kg was given through a gastric tube into the stomach at the same time every day for 7 consecutive days in group AI.In Ⅰ and AI groups,1.5％ isoflurane was inhaled for 6 h with fresh gas flow of 2 L/min at 1 day after the end of administration.Open field test and Morris water maze test were performed at 1 day after the end of anesthesia.The mice were sacrificed at 1 day after the end of Morris water maze test,and hippocampi were isolated for determination of caspase-3,Bax and Bcl-2 expression (by Western blot) and contents of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α) and soluble Aβ1-42 in hippocampal tissues (by enzyme-linked immunosorbent assay).Results There was no significant difference in the parameters of open field test among the three groups (P＞0.05).Compared with group C,the escape latency was significantly prolonged at each time point,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were increased,the expression of caspase-3 and Bax was up-regulated,and Bcl-2 expression was down-regulated in Ⅰ and AI groups (P＜0.05).Compared with group Ⅰ,the escape latency was significantly shortened at each time point,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were decreased,the expression of caspase-3 and Bax was downregulated,and Bcl-2 expression was up-regulated in group AI (P＜0.05).Conclusion Atorvastatin preconditioning can improve cognitive function in isoflurane-anaesthetized mice,and the mechanism may be association with attenuating hippocampal inflammatory responses,inhibiting over-expression of Aβ1-42 and inhibiting neuronal apoptosis.
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Objective To investigate the effects of high dose atovastatin administration on platelet activity and ventricular remodeling of patients with ST-Segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI).Methods A total of 260 STEMI patients who hospitalized in our Department of Cardiology from June 2012 to December 2013 was enrolled and randomly divided into two groups:controlled group (n =140) and high dose atorvastatin group (n =120).Indicators of platelet activities including mean platelet volume (MPV),platelet large cell ratio (P-LCR),blood CD62p,and glucose protein Ⅱ b/Ⅲa (PAC-1) were measured before and 48 hours after PCI.TIMI myocardial perfusion grade (TMPG) after PCI was recorded and patients accepted ultrasound cardiogram (UCG) examinations 5 ～7 days after PCI and 6 months after discharge.After PCI,Patients were followed up for 6 months,statin-associated liver impairment,myopath and major adverse cardiac events (MACE) happened during follow-up periods were recorded.Results MPV,P-LCR,CD62p,and PAC-1 in patients of high dose atorvastatin group were less than controlled group and TMPG were better than controlled group [(12.96±1.73)fl vs (14.18 ± 1.86)fl,P ＜0.05;(29.12 ±5.83)％ vs (30.66 ±6.12)％,P ＜ 0.05;(45.36±5.24)％ vs (48.44±4.75)％,P ＜0.01;(74.61 ±5.57)％ vs (78.55±5.78)％,P ＜0.01].Six months after PCI,UCG examination showed that Left ventricular end-diastolic volume (LV-EDV),left ventricular end-systolic volume (LVESV) and left ventricular mass index (LVMI) in high dose group were less than controlled group while the left ventricular ejection fraction (LVEF) was higher than controlled group [(110.46 ±8.86)ml vs (112.61 ±8.5)ml,P ＜0.01;(60.16 ±6.13)ml vs (63.52 ± 5.54)ml,P ＜0.01;(1O1.69±4.35)g/m2 vs (103.96 ±4.17)g/m2,P ＜0.05;(50.08 ±3.78)％ vs (48.47 ± 4.12) ％,P ＜ 0.05].After 6 months of follow-up,the incidence rate of statin-associated liver impairment and myopathe had no significant difference between two groups and Kaplan-Meier survival analysis showed patients of two groups had significantly different cumulative non-events survival rates (91.7％ vs 82.4％,Log rank =4.409,P =O.036).Conclusions Loading dose atorvastatin before PCI combined high maintenance dose after PCI can inhibit platelet activation and improve myocardial perfusion levels of patients with STEMI underwent primary PCI.It also can reduce Left ventricular remodeling and improve patient's prognosis without increasing side effects.
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Objective To investigate the therapeutic effects of the losartan combined with atorvastatin on patients with diabetic nephropathy (DN).Methods 122 patients with DN were randomly divided into two groups,61 cases in the control group were received conventional therapy and added the losartan,61 cases in the observation group were treated by atorvastatin on the basis of the control group.The treatment time was 12weeks for each group.After 12 weeks,the systolic blood pressure (SBP),diastolic blood pressure (DBP),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),fasting blood glucose (FBG),urinary albumin excretion rate (UAER),serum creatinine (Scr),and glycosylated hemoglobin (HbAIc) were measured.Results The total effective rate was 93.44％ in the observation group,and 75.41％ in the control group,with a statistically significant difference between two groups (x2 =7.54,P ＜ 0.01).After 12 weeks,the SBP and DBP were all changed more than before,DBP decreased more significantly (SBP:t =16.25,17.34,P ＜0.01 ;DBP:t =18.10,17.04,P ＜0.01); FBG,UAER,and HbAlc in the control group were significantly reduced (P ＜ 0.05) ; the TG,TC,LDL,-C HDL,-CFBG,UAER,Scr,and HbAlc of the observed group were significantly reduced more,too.TG,TC,UAER,and Scr of the observed group were significantly lower than the control group (P ＜ 0.05).Conclusions The losartan combined with atorvastatin that were used to treat patients with DN can reduce the urine albumin and protect the renal function.
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ObjectiveTo investigate the effects of 5(S),6(R),7-trihydroxyheptanoic acid methyl ester (BML-111) on pregnant mice with fetal growth restriction(FGR) induced by antenatal dexamethasone and its probable mechanism. MethodsThe mice were mated overnight,with day 1 of pregnancy designated as the day on which spermatozoa were presented in a vaginal smear.The pregnant mice were then randomly divided into control group,dexamethasone group and BML-111 group.From 9 to 14 days of pregnancy,pregnant ICR mice of control,dexamethasone and BML-111 group were treated separately with saline,dexamethasone(5 mg/kg) and dexamethasone at 8:00 am,and two hours later they were treated separately again with 1 mg/kg saline,saline and BML-111.On the day 18 of gestation,they were sacrificed after blood were collected from their eyeballs.The serum lipoxin A4 was measured with enzyme-linked immunosorbent assay. Fetuses were delivered by cesarean section; the placenta and uterus were immediately removed and frozen.Gene expressions of 11β-hydroxysteroid dehydrogenase 2 ( 11β-HSD2 ),interleukin-1β (IL-1β) in placenta and lipoxin A4 receptor-formyl peptide receptor 3 (FPR3)in uterine were detected by reverse transcriptionpolymerase chain reaction and compared with analysis of variance.The 11β-HSD2 protein in mice placenta was detected by immunohistochemistry. ResultsThe mean fetal weight of dexamethasone group was (0.823±0.054) g,lower than that of the control group and BML-111 group [(1.103±0.218) g and (0.992 ± 0.207) g] (t =- 4.108 and - 2.890,P ＜ 0.05 respectively).Protein expression of 11β-HSD2 in dexamethasone group (0.030±0.019) was weaker than that in control group (0.058±0.015,t=-3.107,P＜0.05) or in BML-111 group (0.049±0.026,t=-2.211,P＜0.05).The expression of 11β-HSD2 mRNA in dexamethasone group (0.457±0.062) was lower than that in control group (0.943±0.057,t=-9.418,P＜0.05) or in BML-111 group (0.698±0.071,t=-4.617,P＜0.05).Expression of IL-1β mRNA in dexamethasone group (0.543±0.103)was less than that in control group (0.710± 0.085,t=-3.736,P＜0.05) but more than that in BML-111 group (0.229 ±0.031,t=7.025,P＜0.05). The expression of FPR3 mRNA in dexamethasone group (0.323 ± 0.019) was less than that in control group (0.857 ± 0.057,t =-14.630,P＜0.05) or in BML-111 group (0.499 ±0.050,t=-4.822,P＜0.05).The serum concentration of lipoxin A4 in dexamethasone group was lower than that in control group [(64.463±22.144) pg/ml vs (101.610±24.916) pg/ml,t=3.152,P＜0.05].ConclusionsBML-111 regulate the expression of 11β-HSD2 and then protect against FGR resulted from too much prenatal application of dexamethasone.
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Objective To investigate the anti-inflammatory impacts of in the progression of Alzheimer' s disease (AD) in the rat model induced by β-amyloid 1-42 (Aβ1-42 ). Methods Sixty healthy male Wistar rats (weight 250--300 g) were randomly divided into 4 groups: control group, model group, statins control group and statins treatment group, 15 in each group. Rats model were established via intracerebroventricular injection of A13, and then atorvastatin (5 mg·kg-1·d-1) were given to the treatment group for 3 weeks, saline to the control group. Water Maze was used to observe learning and memory ability changes in rats, and expression of inflammatory eytokines IL-1β, IL-6 and TNF-α in the hippocampus were repectively detected by immunohistochemical technique. Furthermore, HE staining patterns, hippoeampns neurons and glial cells in the small ultra structural changes were observed under light microscope and electron microscope respectively. Results The model rats resulted in decreased learning and memory abihties ( the escaping latency: 12. 0 ± 1.2, 41.3 ± 3.4, t = 18. 0363, P < 0. 01 ) and increased secretion of the brain inflammatory factor compared with the controls with statistically significant difference (IL-1β:53.5 ± 2.4, 101.0 ± 3. 8, t = 23. 8246, P < 0. 01 ). Atorvastatin treatment group improved learning and memory performance ( the escaping latency: 25. 7 ± 1.6, 41.3 ± 3.4, t = 9. 1076, P < 0. 01 ), reduced the secretion of inflammatory factors in the hippocampus, compared with the model rats (IL-1β:60.0±3.4,101.0±3.8, t = 18.0231, P <0.01). There were less injured nerve cells and proliferated glial cells in the atorvastatin treatment group than in the model group. Conclusions Atorvastatin plays an anti-inflammatory role in the progression of Alzheimer's disease, reducing the nerve cell damage and improving learning and memory ability.