Objective To evaluate the effectiveness and safety of simvastatin 40 mg daily use in treatment of coronary heart disease. Methods The study was designed as before-after study in the same patients. One hundred and sixty seven patients with coronary heart disease were prescribed simvastatin 40 mg daily for 3 and 6 months. Total cholestero (TC), low-density lipoproteins cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerldes (TG), ALT and creatine kinase (CK) in serum before therapy and at the end of 3 months and 6 months treatment were dectected. Continuous data were analyzed by standard difference of blocked randomization and described by mean±SD. Dunnet-t test was used for multiple comparison of trial and control groups. Statistical difference was set up at P＜0.05. Success rate was assessed by chi square test at the end of 3 and 6 months treatment. Results Simvastatin 40 mg/d significantly decreased the level of TC (P＜0.000 5), LDL-C (P＜0.000 5), TG (P＜0.05), and could elevate HDL-C (P＜0.05). There were 39.5% of patients whose LDL-C reduced below 70 mg/dl. One patient whose CK raised 5.6 times of upper line of normal range and 4 patients whose ALT raised more than 2 times of upper line of normal range withdrew. The reliability of simvastatin 40 mg/d was relatively good. Conclusions Simvastatin 40 mg/d could significantly improve the lipid profile, and is relatively reliable in treatment of coronary heart disease.
ObjectiveTo systematically review the efficacy and safety of simvastatin and its different doses in the adjunct therapy of chronic obstructive pulmonary disease (COPD).MethodsPubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data, CBM and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on adjunct therapy of simvastatin in patients with COPD from inception to May 15th, 2020. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies; then, meta-analysis was performed by using Stata 14.0 software.ResultsA total of 22 RCTs involving 2 377 patients were included. The results of meta-analysis showed that treatment with 20 mg simvastatin could improve FEV1%pred, FEV1/FVC, and reduce inflammatory indexes such as CRP, hs-CRP, IL-8 and TNF-α, while 40 mg failed to improve. Simvastatin could reduce COPD score (CAT), but failed to increase the 6-minute walking distance or alleviate acute exacerbation.ConclusionsCurrent evidence shows that treatment with 20 mg simvastatin can improve pulmonary function, reduce inflammatory index and optimize CAT score in COPD patients, but it cannot increase the 6-minute walking distance and reduce the number of acute exacerbations of COPD. Due to the limited quantity and quality of included studies, the above conclusions are needed to be verified by more high-quality studies.
目的:观察辛伐他汀、吡格列酮和苯磺酸左旋氨氯地平联合治疗代谢综合征疗效。方法:76例初诊代谢综合征患者,服用吡格列酮15mg/d、苯磺酸左旋氨氯地平25mg/d、辛伐他汀10mg/d,疗程1个月。观察治疗前后血压、腰围、体重指数、血糖、血胰岛素、血尿酸和血脂水平等变化。结果:患者治疗后血糖、血脂、胰岛素水平、血压均明显降低,差别有统计学意义(Plt;001)。腰围、体重指数略有下降,无统计学意义,血尿酸变化不明显。结论:吡格列酮、辛伐他汀和苯磺酸左旋氨氯地平联合治疗代谢综合征能够改善胰岛素抵抗和代谢异常,疗效可靠、服药简单、依从性好,效价比合理,无不良反应。
Objective To investigate the effect of simvastatin on inducing endothel ial progenitor cells (EPCs) homing and promoting bone defect repair, and to explore the mechanism of local implanting simvastatin in promoting bone formation. Methods Simvastatin (50 mg) compounded with polylactic acid (PLA, 200 mg) or only PLA (200 mg) was dissolved in acetone (1 mL) to prepare implanted materials (Simvastatin-PLA material, PLA material). EPCs were harvested from bone marrow of 2 male rabbits and cultured with M199; after identified by immunohistochemistry, the cell suspension of EPCs at the 3rd generation (2 × 106 cells/mL) was prepared and transplanted into 12 female rabbits through auricular veins(2 mL). After 3 days, the models of cranial defect with 15 cm diameter were made in the 12 female rabbits. And the defects were repaired with Simvastatin-PLA materials (experimental group, n=6) and PLA materials (control group, n=6), respectively. The bone repair was observed after 8 weeks of operation by gross appearance, X-ray film, and histology; gelatin-ink perfusion and HE staining were used to show the new vessels formation in the defect. Fluorescence in situ hybridization (FISH) was performed to show the EPCs homing at the defect site. Results All experimental animals of 2 groups survived to the end of the experiment. After 8 weeks in experimental group, new bone formation was observed in the bone defect by gross and histology, and an irregular, hyperdense shadow by X-ray film; no similar changes were observed in control group. FISH showed that the male EPC containing Y chromosome was found in the wall of new vessels in the defect of experimental group, while no male EPC containing Y chromosome was found in control group. The percentage of new bone formation in defect area was 91.63% ± 4.07% in experimental group and 59.45% ± 5.43% in control group, showing significant difference (P lt; 0.05). Conclusion Simvastatin can promote bone defect repair, and its mechanism is probably associated with inducing EPCs homing and enhancing vasculogenesis.
Objective To evaluate the mechanisms of p42/p44 kinase phosphorylation in cell models and to investigate the effect of simvastatin on the prevention and treatment of aseptic loosening of prosthesis by observing the influence of simvastatin on the levels of tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) of human peri pheral blood mononuclear cell (PBMC) challenged with titanium particles. Methods PBMC from 45 mL peripheral blood of healthy adult voluntary donators, were separated and cultured, and divided into 5 groups according to different culturemedium: group A, PBMC and titanium particles; group B, PBMC and titanium particles with 1 × 10-5 mol/L simvastatin; group C, PBMC and titanium particles with 1 × 10-6 mol/L simvastatin; group D, PBMC and titanium particles with 1 × 10-7 mol/L simvastatin; and group E, PBMC and titanium particles with the extracellular signal-regulated kinase (ERK1/2) inhibitor U0126. The contents of TNF-α and MCP-1 were tested by ELISA after 24 hours of culture. PBMC were pretreated with different medium grouping as groups A, B, C, D, and E for 60 minutes, and were challenged with titanium particles for 30 minutes and 60 minutes, then the level of ERK1/2 expression was tested by Western blot. Results In groups A, B, C, D, and E, the absorbance (A) values of TNF-α were 1.115 5 ± 0.243 6, 0.693 6 ± 0.354 3, 0.695 7 ± 0.387 3, 0.716 4 ± 0.478 9, and 0.263 5 ± 0.101 6, respectively; and the A values of MCP-1 were 1.421 0 ± 0.105 3, 0.915 1 ± 0.411 3, 1.003 5 ± 0.464 2, 1.102 0 ± 0.353 9, and 0.271 3 ± 0.145 1, respectively. The levels of TNF-α and MCP-1 in group A were significantly higher than others, showing significant differences (P lt; 0.05). There were significant differences between group E and groups B, C, and D (P lt; 0.05), between group B and groups C, D (P lt; 0.05); no significant difference between group C and group D (P gt; 0.05). Western blot results showed the expression of ERK1/2 in all groups at 30 minutes and 60 minutes of culture. The levels of ERK1/2 expression were 1.612 1 ± 0.068 2, 1.078 1 ± 0.072 8, 1.268 7 ± 0.223 1, 1.439 7 ± 0.180 1, and 0.732 0 ± 0.110 4 in groups A, B, C, D, and E, respectively; showing significant differences between groups (P lt; 0.05). Conclusion ERK1/2 is a phosphorylated protein after stimulated by wear particles; it is also one of the most important cell signal ing activation of macrophage. Simvastatin can inhibit the expression of bone absorptive factors induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis.
Objective To find an ideal material for repairing bone defect by local implanting simvastatin compounded with poly-lactic acid (PLA) into the radial critical size defects of rabbits, and to observe the reparative effect and type of bone formation induced by simvastatin. Methods Twelve 4-months-old male New Zealand white rabbits (2.3-2.8 kg) with 22 mm radial critical size defects on both sides were randomized into 4 groups (all n=3). Right side and left side of every rabbit were set as controls with each other. The left defects (experimental groups) of groups A, B, and C were implanted with cyl inder-l ike compound scaffolds containing 50, 100, and 200 mg of simvastatin (fixed with 250 mg PLA), or auto-bonegraft as group D, respectively. The right defects of groups A, B, and C were implanted with scaffolds containing only 250 mg PLA. The right defects of group D were left without any treatment. Digital X-ray images of bone defects were taken 8 and 16 weeks after operation, X-ray was scored double bl ind and X-ray pixel value was measured. Animals were euthanized16 weeks postoperatively. CT was appl ied to analyze new bone formation volume in the defects. In addition, orphologicalcharacters of new bones were observed through micro-CT and histology. Results X-ray films showed that the bone defect of each experimental side had much cloud-l ike callus, and the bone stump were not clear 8 weeks after operation; and the cortex in the defect was continuous and the medullary was recanal ized 16 weeks after operation. In control sides, the cortexes were discontinuous and the ends of fractures were sclerified. At 8 and 16 weeks after operation, the X-ray scores, pixel values and the CT volume percentage of new bone in experiment sides were all significantly higher than those in control sides (P lt; 0.05). The X-ray scores of experimental sides in groups C and D were significantly higher than those in groups A and B 8 weeks after operation (P lt; 0.05), and the X-ray scores of experimental sides in groups B and D were significantly higher than those in groups A and C 16 weeks after operation (P lt; 0.05). The X-ray pixel values of experimental sides of group B were significantly higher than those of groups A, C, and D 8 weeks after operation (P lt; 0.05). The new bone formation volume of experimental side of groups B and D was higher than that of groups A and C (P lt; 0.05), and group D was significantly higher than that of group B (P lt; 0.05). Micro-CT showed bone defects of experimental sides of group B had totally healed, with connected medullary cavities and continuous bone cortex, on the contrary bone defects of control sides of group B did not healed completely. Histological observation showed better bone remodeling effects of the experimental sides than control sides, with connected medullary cavities and continuous bone cortex. And the osteogenetic type was endochondral ossification. Conclusion Local implantation of simvastatin can promote repairing rabbit radial critical bone defect, 100 mg is the best dose of repairing the bone defects.
目的：研究羟甲戊二酰辅酶A还原酶抑制剂辛伐他汀治疗慢性肾功能不全的临床疗效。方法：选择慢性肾功能衰竭患者共40例，随机分成两组，在原有基础治疗上治疗组20例患者予以辛伐他汀治疗，对照组20例单纯以基础治疗，在24周时监测TC、TG、24 h尿蛋白、Scr、BUN、C-反应蛋白的值。结果：与治疗前相比，两组TC、TG、24 h尿蛋白、Scr、BUN、C-反应蛋白均明显下降，与对照组相比，治疗组血脂有显著下降（P＜0.01）而且24h尿蛋白、Scr、BUN、C-反应蛋白均明显下降(P＜0.05)。结论：辛伐他汀能降低蛋白尿，延缓慢性肾功能不全的进展
ObjectiveTo investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism.MethodsTwelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation.ResultsVascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001).ConclusionIntravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.
Objective To confirm the stimulating effect of simvastatin on BMSCs of SD rats osteogenic differentiation, and to further study the role of Wnt signal ing pathway in this process. Methods BMSCs derived from the tibia and femur of 6-week-old female SD rats were cultured in vitro．Two groups were establ ished: control group and experimental group. After the 2nd passage, the cells of experimental group were treated with simvastatin (1 × 10-7mol/L) and the cells of control group with absolute ethyl alcohol and PBS. ALP staining was used at 7 days and von Kossa staining was appl ied at 28 days to assess osteoblastic differentiation and mineral ization. Real-time quantitative PCR was performed to evaluate theexpressions of Axin2, β-catenin, osteocalcin (OC), frizzled-2, Lef-1, and Wnt5a mRNA at 7 days and 14 days after simvastatin treatment. Results The observation of inverted phase contrast microscope showed that the majority of cells were polygonal and triangular in the experimental group, and were spindle-shaped in the control group at 7 days. The ALP staining showed blue cytoplasm, the positive cells for ALP staining in the experimental group were more than those in the control group at 7 days. The von Kossa staining showed that mineral ization of extracelluar matrix at 28 days in two groups, but the mineral ization in the experimental group was more obvious than that in the control group. The expression of Axin2 mRNA was significantly lower, and frizzled-2, Lef-1 mRNA were significantly higher in the experimental group than in the control group (P lt; 0.05) at 7 days, while the mRNA expressions of Axin2, OC, frizzled-2, Lef-1, and Wnt5a were significantly higher in the experimental group than in the control group at 14 days (P lt; 0.05). Conclusion Simvastatin can promote the osteogenic differentiation of BMSCs and change the expression of mRNA of some components of Wnt signal ing pathway.
Objective To investigative the effects of combination treatment with simvastatin and aspirin in a rat model of monocrotaline-induced pulmonary hypertension. Methods Sixty male Sprague-Dawley rats were randomly divided into a control group, a simvastatin group, an aspirin group, and a combination treatment group. The control group received monocrotaline injection subcutaneously to induce pulmonary hypertension. Simvastatin ( 2 mg/kg) , aspirin ( 1 mg/kg) , or simvastatin ( 2 mg/kg) + aspirin ( 1 mg/kg) was administered once daily to the rats of treatment groups respectively for 28 days after monocrotaline injection. Mean pulmonary arterial pressure ( mPAP) was detected by right heart catheter.Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysissystem. Interleukin-6 ( IL-6) level in lung tissue was determined by ELISA.Results Compared with the control group, simvastatin or aspirin decreased mPAP [ ( 34. 1 ±8. 4) mm Hg, ( 38. 3 ±7. 1) mmHg vs.( 48. 4 ±7. 8) mmHg] and increased arterial wall diameter significantly ( P lt; 0. 05) . The combination treatment group showed more significant improvement in mPAP, RVHI and pulmonary arterial remodeling compared with each monotherapy ( P lt;0. 05) . Moreover, the combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score. Conclusions Combination therapy with simvastatin and aspirin is superior in preventing the development of pulmonary hypertension. The additive effect of combination therapy is suggested to be ascribed to anti-inflammation effects.