Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolmic rats

This study was conducted to investigate the hypocholesterolemic effect of simvastatin (30 mg/kg BW) and antioxidant effect of coenzyme Q10 (CoQ10, 15 mg/kg BW) or green tea (5%) on erythrocyte Na leak, platelet aggregation and TBARS production in hypercholesterolemic rats treated with statin. Food efficiency ratio (FER, ADG/ADFI) was decreased in statin group and increased in green tea group, and the difference between these two groups was significant (p<0.05). Plasma total cholesterol was somewhat increased in all groups with statin compared with control. Plasma triglyceride was decreased in statin group and increased in groups of CoQ10 and green tea, and the difference between groups of statin and green tea was significant (p<0.05). Liver total cholesterol was not different between the control and statin group, but was significantly decreased in the group with green tea compared with other groups (p<0.05). Liver triglyceride was decreased in groups of statin and green tea compared with the control, and the difference between groups of the control and green tea was significant (p<0.05). Platelet aggregation of both the initial slope and the maximum was not significantly different, but the group with green tea tended to be higher in initial slope and lower in the maximum. Intracellular Na of group with green tea was significantly higher than the control or statin group (p<0.05). Na leak in intact cells was significantly decreased in the statin group compared with the control (p<0.05). Na leak in AAPH treated cells was also significantly reduced in the statin group compared with groups of the control and CoQ10 (p<0.05). TBARS production in platelet rich plasma was significantly decreased in the groups with CoQ10 and green tea compared with the control and statin groups (p<0.05). TBARS of liver was significantly decreased in the group with green tea compared with the statin group (p<0.05). In the present study, even a high dose of statin did not show a cholesterol lowering effect, therefore depletion of CoQ10 following statin treatment in rats is not clear. More clinical studies are needed for therapeutic use of CoQ10 as an antioxidant in prevention of degenerative diseases independent of statin therapy.     

不同剂量辛伐他汀对肾病综合征高脂血症的近期疗效

目的 :观察辛伐地他汀 -舒降之对肾病综合征高脂血症的近期疗效及安全性 ,比较不同剂量辛伐他汀的降脂作用。方法 :72例均系肾综合并高脂血症的患者 ,随机分治疗组 (5 6例 )和对照组 (16例 ) ,在积极治疗原发病的同时 ,治疗组给予服辛伐他汀每晚 5～ 2 0mg ,14例混合性高脂血症患者同时服用非诺贝特 ;对照组未用降脂药。观察治疗前及治疗后 1周、2周血脂全套 (TC ,TG ,LDL和HDL)、肝功能 (AST ,ALT ,TP和ALB)、肾功能 (BUN ,Scr)、及尿蛋白定量的变化。结果 :辛伐他汀每晚 2 0mg服用 1周可使 6 3%的患者总胆固醇 (TC)下降 33% ,服用 2周可使 84%的患者血TC降至正常 ;单用辛伐他汀在降低TC的同时 ,可使甘油三酯 (TC)下降 43.16 % ,若与非诺贝特合用可使TG下降达 6 4.2 2 % ,未见不良反应发生 ;辛伐他汀的降脂作用与剂量及用药时间密切相关 ,2 0mg >10mg >5mg ,每晚服用 5mg共 2周仅能使 6 0 %的患者TC下降 12 .5 %。结论 :辛伐他汀 (每晚 2 0mg)能安全、快速有效降低肾病综合征患者的高脂血症 ,而对减少尿蛋白、改善肾功能近期无作用     

一氧化氮在糖皮质激素性骨质疏松发病中的作用和辛伐他汀对骨代谢的影响

目的探讨一氧化氮(NO)在糖皮质激素性骨质疏松症(GC-OP)发病机制中的作用和辛伐他汀对NO的调控。方法6个月龄SD雄性大鼠随机分为3组,实验组(A)给予辛伐他汀和地塞米松,模型组(B)给予生理盐水和地塞米松,对照组(C)给予生理盐水。8周后观察第3腰椎显微结构、股骨组织形态计量学、腰椎诱生型一氧化氮合酶(i NOS)和内皮细胞型一氧化氮合酶(eNOS)免疫组织化学。结果3组血清NO含量差异无统计学意义(P>0.05)。A组显微结构与C组相似,B组呈骨质疏松表现。3组eNOS表达的平均灰度值与平均积分吸光度分别为(179.08±4.38)与(0.455±0.019)、(169.42±3.00)与(0.401±0.010)、(181.08±2.31)与(0.463±0.150)。A组明显高于B组(P<0.01),与C组差异无统计学意义(P>0.05)。A组的骨体积、类骨质表面、类骨质宽度和成骨表面分别为(53.46±2.49)%、(9.52±1.11)%、(3.25±0.19)μm、(9.20±1.37)%,均比B组(42.48±1.95)%、(7.34±0.66)%、(2.72±0.32)μm、(7.43±0.58)%显著增高(P<0.01),与C组(54.69±1.87)%、(9.44±1.13)%、(3.44±0.28)μm、(9.83±1.06)%差异无统计学意义(P>0.05)。3组骨吸收表面的差异无统计学意义(P>0.05)。结论eNOS依赖性NO的低表达是GC-OP的重要发病机制,辛伐他汀增强eNOS的表达而有效预防该症的发生。     

高半胱氨酸促THP-1巨噬细胞表达单核细胞趋化蛋白-1和辛伐他汀的调节作用

目的 :研究高半胱氨酸 (Hcy)对人单核细胞系 (THP 1)分化而来的巨噬细胞 (THP 1巨噬细胞 )表达单核细胞趋化蛋白 1(MCP 1)的影响及辛伐他汀可能存在的调节作用。方法 :在培养的THP 1中加入佛波脂(PMA) ,使终浓度为 2 0ng/ml,培养 4 8h ,细胞贴壁呈巨噬细胞样分化。他汀组和Hcy组分别加入含有辛伐他汀(10 μmol/L ,5 0 μmol/L)或不含辛伐他汀完全培养基 37℃培养 2 4h ,再加入含DL Hcy(0 1mmol/L)完全培养基 ,对照组只加完全培养基 ,培养 2～ 2 4h ,上清离心 5 0 0g ,10min ,- 2 0℃保存。用ELISA法检测上清中MCP 1蛋白的量。每孔重复 3次。结果 :与对照组比较 ,加入 0 1mmol/LHcy可使THP 1巨噬MCP 1蛋白表达升高 ,4h后显著升高 (P <0 0 5 ) ,6h达高峰 (P <0 0 1) ,12h后逐渐下降 (P <0 0 5 ) ,分别为对照组的 2 9倍、5 8倍和 2 6倍 ,2 4h与对照组无显著差异。 10 μmol/L、5 0 μmol/L辛伐他汀分别使与Hcy共孵育 6h(高峰时间 )MCP 1蛋白量下降至Hcy组的 5 7 11%、2 3 6 4 %。结论 :病理浓度的Hcy(0 1mmol/L)可时间依赖性促进THP 1巨噬细胞表达MCP 1蛋白 ,该作用可被辛伐他汀下调。     

辛伐他汀治疗急性脑梗死的疗效观察

目的 探讨辛伐他汀治疗急性脑梗死临床疗效.方法 观察123例经颅脑CT或MRI证实的急性脑梗死患者治疗前后临床神经功能缺损的变化,并与对照组进行比较.结果 辛伐他汀治疗急性脑梗死有良好效果,其中治愈30例(24.39%),显著进步59例(47.97%),进步27例(21.95%),总有效率94.31%.未发现明显不良反应.结论 辛伐他汀治疗急性脑梗死安全有效.     

低分子肝素钙联合辛伐他汀治疗不稳定型心绞痛疗效观察

目的探讨低分子肝素联合辛伐他汀治疗不稳定型心绞痛的疗效。方法将100例不稳定型心绞痛患者随机分为对照组50例和观察组50例。对照组仅采取常规治疗（硝酸酯类、β-受体阻滞剂、钙拮抗剂、阿司匹林等），观察组在常规治疗的基础上加用低分子肝素和辛伐他汀，观察比较各组的疗效。结果观察组总有效率为90．0％，对照组总有效率为60．0％，两组疗效比较差异有显著性意义（P〈0．05）。结论低分子肝素联合辛伐他汀治疗不稳定型心绞痛取得满意的疗效。     

The influence of simvastatin alone or in combination with gemfibrozil on plasma lipids and lipoproteins in patients with type III hyperlipoproteinemia

Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo Apolipoprotein - CPK creatine phosphokinase - GGT gamma-glutamyl transpeptidase - HDL high density lipoproteins - HLP hyperlipoproteinemia - HMG CoA 3-hydroxy-3-methyl glutaryl coenzyme A - IDL intermediate density lipoproteins - LDL low density lipoproteins - TG triglycerides - VLDL very low density lipoproteins     

辛伐他汀对大鼠心肌组织中低氧诱导因子1α表达的影响

目的：了解他汀类降脂药对低氧诱导因子1α（HIF1α）表达的影响,探讨其除降脂以外的抗心肌缺血作用机制。方法：将大鼠随机分为对照组、辛伐他汀组、心肌缺血组和辛伐他汀＋心肌缺血组。给辛伐他汀药4周后心肌缺血组和辛伐他汀＋心肌缺血组通过结扎冠状动脉左前降支致大鼠急性心肌缺血。分别用逆转录聚合酶链式反应(RT-PCR)法和Western blotting法及免疫组化法检测各组心肌组织中HIF1α mRNA 和蛋白的表达。结果：辛伐他汀和心肌缺血组均能使HIF1α表达明显高于对照组(P<0.01)，心肌缺血前辛伐他汀预处理可使HIF1α表达进一步增高(P<0.01)。结论：辛伐他汀可能是通过上调HIF1α表达促进新生血管形成，治疗心肌缺血。     

含辛伐他汀药物血清对兔血管平滑肌细胞增殖的直接作用及意义

目的 :探讨辛伐他汀对体外培养兔血管平滑肌细胞增殖的影响及意义。方法 :16只雄性新西兰兔随机分为血清对照组和三个不同剂量的辛伐他汀亚组 (每日分别给予辛伐他汀 5mg/kg、10mg/kg、15mg/kg) ,7天后采血并混合每组 4只兔血 ,无菌分离制备三亚组的辛伐他汀含药血清。采用内皮素 1(ET 1)刺激正常喂饲原代培养兔主动脉血管平滑肌细胞的方法 ,建立血管平滑肌细胞增殖模型。采用MTT及3H TdR法检测各组辛伐他汀含药血清对血管平滑肌细胞增殖的作用。结果 :与不含药的正常对照组相比 ,不同亚组辛伐他汀含药血清呈剂量依赖性抑制血管平滑肌细胞增殖 (P <0 .0 1～0 .0 5 )。结论 :兔口服辛伐他汀后的血清具有抑制血管平滑肌细胞增殖的作用