不同剂量他汀类药物对经皮冠状动脉介入治疗的老年ST段抬高型急性心肌梗死患者的影响

目的 探讨不同剂量阿托伐他汀、瑞舒伐他汀、辛伐他汀对接受经皮冠状动脉介入治疗(PCI)的老年ST段抬高型急性心肌梗死(STEMI)患者的影响。方法 前瞻性选取接受PCI的180例STEMI患者作为研究对象,采用随机数字表法分为A组、B组、C组、D组、E组、F组,每组30例。A组口服低剂量辛伐他汀,B组口服高剂量辛伐他汀,C组口服低剂量阿托伐他汀,D组口服高剂量阿托伐他汀,E组口服低剂量瑞舒伐他汀,F组口服高剂量瑞舒伐他汀。比较各组患者血清炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)]、心肌损伤标志物[肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白T(cTnT)、N末端脑钠肽前体(NT-proBNP)]、心功能指标[左心室射血分数(LVEF)、心脏指数(CI)、心排血量(CO)]水平、ST段回落情况及不良心血管事件、不良反应发生情况。结果 术后1 d、术后1个月时,A组、B组、C组、D组、E组、F组的IL-6、hs-CRP、TNF-α水平均依次降低,差异有统计学意义(P<0.05);术后1 d、术后1个月时,A组、B组、C组、D组、E组、F组的cTnT、CK-MB、NT-proBNP水平均依次降低,差异有统计学意义(P<0.05);术后1个月时,A组、B组、C组、D组、E组、F组的LVEF、CO、CI均依次升高,差异有统计学意义(P<0.05);A组、B组、C组、D组、E组、F组的ST段回落者占比依次升高,差异有统计学意义(P<0.05);各组患者不良心血管事件总发生率、不良反应总发生率比较,差异均无统计学意义(P>0.05)。结论 低剂量、高剂量的阿托伐他汀、瑞舒伐他汀、辛伐他汀应用于PCI术后STEMI患者,均可有效减轻炎症反应,改善心肌功能,促进ST段回落,其中高剂量瑞舒伐他汀效果最佳。

Simvastatin对大鼠坐骨神经crush损伤修复作用研究

目的探讨他汀类(statins)药物Simvastatin在大鼠坐骨神经损伤修复中的作用及可能的作用机制。方法制作SD大鼠标准坐骨神经钳夹损伤(crush)模型后,分别予Simvastatin和溶媒对照干预2周。手术前后不同时间点进行趾展功能指数测定、神经电生理学、血脂水平、血清IL-6检测和组织学评价。结果Simvastatin干预组与对照组比较,趾展功能指数在术后5d和8d显著增大(P<0.05),足趾展开速度快;2周肌肉复合动作电位幅度高,4周神经传导速度快;组织学显示有髓神经纤维数量多,髓鞘厚,排列相对整齐。各组手术前血脂水平无差异,手术后2周均有不同程度的降低,但Simvastatin干预组总胆固醇降低程度最轻,与对照组比较有显著差异(P<0.05);Simvastatin干预组手术后5d,血清IL-6水平明显低于对照组(P<0.05)。结论本研究发现,Simvastatin可能通过抑制免疫炎症反应,维持神经损伤后胆固醇的平衡,促进大鼠坐骨神经损伤的修复和再生。

Simvastatin抑制白介素-6的产生促进大鼠坐骨神经再生

[目的]探讨他汀类(statins)药物S imvastatin促进大鼠坐骨神经修复及其免疫调节机制。[方法]制作SD大鼠坐骨神经钳夹损伤(crush)模型,分别予S imvastatin和溶媒(0.3%羧甲基纤维素钠)对照干预2周,并设立假手术组。手术后作行为学、神经电生理学、组织学计价和血清TNFα-和IL-6检测。[结果]S imvastatin干预组趾展功能指数在术后5、8 d较对照组大,2周肌肉复合动作电位(CMAP)幅度高,4周神经传导速度(NCV)快;手术后5 d,血清IL-6和TNFα-水平均低于对照组,尤以IL-6为明显;S imvastatin干预组神经再生形态优于对照组。[结论]S imvastain可能通过减少血清IL-6和TNFα-的生成,抑制免疫反应,对大鼠坐骨神经crush损伤修复产生促进作用。

棕榈酸诱导斑马鱼脂毒性损伤骨形成抑制模型的建立

目的 建立棕榈酸诱导的斑马鱼脂毒性损伤骨形成抑制模型。方法 将AB品系斑马鱼胚胎分为对照组、棕榈酸组(PA组)和辛伐他汀组(SIM组)。从3 dpf(days post fertilization, dpf)开始,PA组、SIM组给予PA造模。从5 dpf开始,SIM组给予SIM连续给药4 d。9 dpf通过钙黄绿素染色法、尼罗红染色法、甘油三酯及总胆固醇含量测定、q-PCR判断模型是否成功建立。结果 PA显著减少斑马鱼椎骨骨节数目、促进脂质堆积、增加甘油三酯及总胆固醇含量、促进成脂相关基因PPARγ、c/EBPα的表达并抑制成骨相关基因ALP、RUNX2的表达。SIM可以改善PA对斑马鱼的骨形成抑制效应。结论 采用PA给药的方法可成功造成与骨质疏松症(osteoporosis, OP)病理过程相似的脂毒性损伤骨形成抑制模型,该方法简便、灵敏、可控,可用于OP及相关疾病的药物筛选。

辛伐他汀抑制川畸病大鼠心肌损伤

目的探讨辛伐他汀对川崎病大鼠心肌的影响及机制。方法随机将SD雄性大鼠分为对照组、模型组及辛伐他汀组,除对照组外其余两组均利用干酪素酸杆菌提取物构建大鼠川崎病心肌损伤模型。心脏超声及组织学切片观察辛伐他汀对大鼠心功能及心肌结构的影响。ELISA试剂盒检测各组血清中心肌损伤指标及心肌组织炎症因子水平。免疫印迹法检测各组心肌组织中凋亡相关蛋白、高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)通路蛋白的表达水平。结果与对照组比较,模型组大鼠心功能指标水平、抗凋亡蛋白B细胞淋巴瘤-2(Bcl-2)表达显著下降,心肌组织炎症细胞浸润增加,炎症因子水平、促凋亡蛋白Bcl-2关联X蛋白及活化的Caspase-3、HMGB1/RAGE通路蛋白表达升高(P<0.05)。与模型组比较,辛伐他汀组以上各个指标均显著逆转(P<0.05)。结论辛伐他汀可抑制川崎病导致的大鼠心肌损伤,其机制可能与抑制HMGB1/RAGE信号通路有关。

辛伐他汀联合胺碘酮治疗老年心力衰竭合并心房颤动的效果分析

目的:探讨辛伐他汀联合胺碘酮治疗老年心力衰竭合并心房颤动的效果。方法:选取2021年8月—2022年12月西宁市第二人民医院心内科收治的102例老年心力衰竭合并心房颤动患者作为研究对象。根据抛硬币法分为观察组和对照组,各51例。对照组予以胺碘酮单药治疗,观察组在对照组基础上联合辛伐他汀治疗。比较两组实验室指标、心功能、临床治疗效率、心房颤动转复率、不良反应发生率。结果:治疗前,两组C反应蛋白(CRP)、血清总胆固醇(TC)、低密度脂蛋白(LDL-C)水平比较,差异无统计学意义(P>0.05);治疗后,对照组CRP、TC低于治疗前,观察组CRP、TC、LDL-C低于治疗前及对照组,差异有统计学意义(P<0.05)。治疗前,两组左室射血分数(LVEF)、左心房内径(LAD)水平比较,差异无统计学意义(P>0.05);治疗后,对照组LVEF高于治疗前,观察组LVEF高于治疗前及对照组,LAD低于治疗前及对照组,差异有统计学意义(P<0.05)。观察组治疗总有效率和心房颤动转复率均高于对照组,差异有统计学意义(P<0.05)。观察组不良反应总发生率为5.88%;低于对照组的11.76%,但两组间比较,差异无统计学意义(χ^(2)=1.097,P>0.05)。结论:应用辛伐他汀联合胺碘酮治疗老年心力衰竭合并心房颤动的效果较好,可以改善患者心功能,减轻炎症状态,缓解症状,安全性较高。

辛伐他汀联合N-乙酰半胱氨酸治疗支气管哮喘患者的临床效果

目的探讨辛伐他汀联合N-乙酰半胱氨酸治疗支气管哮喘患者的临床效果。方法选取61例支气管哮喘患者作为研究对象,将其随机分为对照组(n=31例)和观察组(n=30例)。对照组给予常规治疗,观察组在对照组的基础上加用辛伐他汀联合N-乙酰半胱氨酸治疗,两组均治疗6周。比较两组患者的临床疗效、治疗前后的肺功能和炎性因子水平,以及治疗期间不良反应的发生情况。结果治疗6周后,观察组患者治疗总有效率高于对照组患者;两组患者呼气峰值流量实测值/预计值、用力肺活量和第1秒用力呼气容积均升高,且观察组患者上述指标均大于对照组患者;两组患者血清白细胞介素-6、白细胞介素-17和肿瘤坏死因子-α水平均降低,且观察组患者上述指标均低于对照组患者(均P<0.05)。治疗期间,两组患者不良反应的发生情况差异无统计学意义(P>0.05)。结论辛伐他汀联合N-乙酰半胱氨酸治疗支气管哮喘患者的临床效果好,可有效地改善患者的肺功能,降低炎性因子水平,减轻气道炎症反应,且不良反应较轻。

不同他汀类降脂药对老年冠心病患者冠状动脉搭桥术后主要不良心血管事件的影响

目的 分析不同他汀类降脂药对老年冠心病患者冠状动脉搭桥(CABG)术后主要不良心血管事件(MACE)发生率的影响。方法 选择2021年10月至2022年10月于我院行CABG治疗的老年冠心病患者92例,根据术后接受不同他汀类降脂药分为辛伐他汀组(44例)与阿托伐他汀组(48例)。对比两组患者的血脂水平、 MACE发生率及不良反应情况。结果 治疗后,两组的血清TC、 TG水平均下降(P <0.05),但组间对比无统计学差异(P>0.05)。两组MACE发生率、不良反应发生率比较无统计学差异(P>0.05)。结论 辛伐他汀与阿托伐他汀均可显著降低老年冠心病患者CABG术后血脂水平,在预防MACE发生及药物安全性方面效果相当。

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

Objective:To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Methods:Sixty SD rat aged 9-12 weeks were chosen and divided into the control group,model group and simvastatintreated group randomly with 20 rats in each group.Rats in the model group and simvastatintreated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model,while rats in the control group were treated with the same amount of normal saline.Then,rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling.Rats in the three groups were given nerve dysfunction score(NDS) and wet-dry weighting method was used to detect the brain water content(BWC) of brain tissues around the lesion of the rats.Then Nissl staining was conducted and the undamaged neurons were counted.Immunohistochemical SP method was applied to count the number of NF-d the immuno fluorκB,TLR4 and IL-1escence method wasβ positive cells in brain tissues around the lesions,an employed to determine the expression levels of NF-κB,TLR4 and IL-1me points were aβ proteins.Results:The NDS results of the simvastatin-treated group at all till significantly higher than those of the model group(P < 0.05);the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods(P < 0.05);the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group(P < 0.05);seven days after treatment,the number of the NF-κB,TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group(P < 0.05),and its expression levels of NF-ower than those of the model group(κB,TLR4 and IL-1P < 0.05).Conclusioβ protein were also significantly lns:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1β proteins in rats with cerebral hemorrhage,and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

Addition of simvastatin to carvedilol non responders: A new pharmacological therapy for treatment of portal hypertension

AIM To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODS One hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient(HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day(increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTS A total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmH g and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mm Hg and 2.8 ± 1.6 mm Hg among responders and non-responders respectively(P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients(42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients(80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects.CONCLUSION Addition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.

Simvastatin Increases the Activity of Endothelial Nitric Oxide Synthase via Enhancing Phosphorylation

3-hydroxy-3-methylgulutaryl-coenzyme A （HMG-CoA） reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of Cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase （eNOS）. In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells （293-eNOS） with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin （10 μm/L） for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline （2889.70±201.51 versus 5630.18＋218.75 pmol/min . mg proteins） （P〈0.01）. Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 （ser） and also 495 （thr） but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate,the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.

Simultaneous determination of ezetimibe and simvastatin in rat plasma by stable-isotope dilution LC-ESI-MS/MS and its application to a pharmacokinetic study

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes： ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 rain. Samples were extracted from plasma by liquid-liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-CIs column using mobile phase that consisted of a mixture of ammonium acetate （pH4.5; 10 mM）-acetonitrile （25：75 v/v）. The method was linear and validated over the concentration range of 0.2--40.0 ng/rnL for simvastatin and 0.05-15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30 → 285.20 and rrdz 425.40 →199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6-14.8% and 2.1-13.4%; and for simvastatin 0.94-9.56% and 0.79-12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.

Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax

BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism.METHODS: Human umbilical vein endothelial cells(HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group(sepsis group) and simvastatin+sepsis serum intervention group(simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and fl ow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR.RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum; however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group.CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.

Effect of simvastatin on paraoxonase 1(PON1) activity and oxidative stress

Objective:To investigate the effect of simvastatin treatment on lipid pr of ile and oxidative stress in hypercholesterolaemic Indian population and determine the effect of simvastatin treatment on the activity of paraoxonase（PON）.Methods:Analyzed initially before medication administration and four months later after medication.Lipid and lipoprotein measurement were done by enzymatic kits,high density lipoprotein（HDL） was determined by phosphotungstic acid precipitation method and low density lipoprotein（LDL） was calculated by Friedewald’s formula.Lipid peroxidation was measured by three markers namely,conjugated diene,total peroxide,and malondialdehyde.Conjugated diene was assayed by Buege and Aust method.Total peroxide was determined by FOX2 method.Malondialdehyde determination was carried out by Flemming method and total antioxidant status was determined by Ozacan.Paraoxonase activity was determined by measuring the absorbance inrease of p-nitrophenol at 405 nm.Arylesterase activity was calculated from the molar coefficient of 1 310 M-1 cm-1.Results:Simvastatin significantly reduced total cholesterol,triglycerides,LDL,conjugated diene,total peroxide and MDA levels,where as antioxidant status was significantly increased.Besides,simvastatin significantly increased PON1 activity towards paraoxon.Conclusions:The results from the current study indicate simvastatin may have important antioxidant properties via increasing PON activity.

Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.

Effect of Taizhi'an Capsule (泰脂安胶囊) Combined with Simvastatin on Hyperlipidemia in Diabetic Patients

To evaluate the effectiveness and safety of Taizhi＇an （泰脂安, TZA） capsule combined with Simvastatin （Sim） in treating hyperlipidemia in diabetes mellitus （DM） patients. Methods： Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results. The serum levels of total cholesterol （TO）, triglycerides （TG） and low density lipoprotein-cholesterol （LDL-C） were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol （HDL-C） was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment （all P〈0.05）, but they did not differ statistically between the two groups （P〉0.05）. There was no significant changes in hemoglobin A1 c （HbA1c）. Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion： In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.

Influence of simvastatin on dopaminergic neurons of lipopolysaccharide—induced rat model of Parkinson's disease

Objective::To investigate the neuroprotective effects of simvastatin on lipopolysaccharide(LPS)-indueed rat model of Parkinson's disease(PD) and the mechanisms involved.Methods:Hemiparkinsonian rat models were induced by stereotaxieal injection of LPS in the right substantia nigra compacts.After 2 weeks of simvastatin treatment,rotational behavior test was performed after the intraperitoneal injection of apomorphine.Expression of tyroxine hydroxylase(TH) and glial fibrillan acidic protein were analyzed through immunohistochemical staining of substantia nigra and striatum,and the level of TNF-α was evaluated using enzyme-linked immunosorbent assay.Results:Comparing with untreated group,behavioral symptoms of the rats were significantly less in the rats that received simvastatin treatment.The TH positive cell count in substantia nigra and striatum were significantly increased(P<0.05) and TNF- α expression was significantly decreased(P<0.05) in simvastatin group compared to untreated group.Conclusions:Simvastatin could effectively inhibit the activation of astrocytes,reduce TNF-α expression,and exert anti-inflammatory effects,and thus protect the dopaminergic neurons in substantia nigra and striatum of the rat model of PD.

The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor-β1,Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket

Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Pretreatment with simvastatin upregulates expression of BK-2R and CD11b in the ischemic penumbra of rats

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment in preventing cerebral ischemia/reperfusion injury in rats using a model of middle cerebral artery occlusion（MCAO）.Rats were pretreated with simvastatin 14 days prior to MCAO induction. At 3, 24, and 48 hours after reperfusion,bradykinin levels in the ischemic penumbra were assayed by ELISA, mRNA levels of bradykinin B2 receptors（BK-2Rs） and CD11b were measured by fluorescent quantitative real-time PCR（RT-PCR）, and co-expression of microglia and BK-2Rs was determined by immunofluorescence. Simvastatin had no effect on bradykinin expression in the ischemic penumbra at any time point. However, the levels of BK-2R and CD11b mRNA in the ischemic penumbra,which were significantly decreased 3 hours after ischemia-reperfusion, were increased in simvastatin-pretreated rats.Moreover, the co-expression of BK-2Rs and microglia was confirmed by immunofluorescence analysis. These results suggest that the beneficial effects of simvastatin pretreatment before cerebral ischemia/reperfusion injury in rats may be partially due to increased expression of BK-2R and CD11b in the ischemic penumbra.