Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig: atorvastatin versus simvastatin.

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauric and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma low-density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins were equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo-B) levels. Atorvastatin and simvastatin treatments yielded LDL particles that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression of atherosclerosis, these parameters were analyzed after statin treatment. Atorvastatin and simvastatin treatment decreased the susceptibility of LDL particles to oxidation by 95% as determined by the formation of thiobarbituric acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high-density lipoprotein (HDL) and the apo-B-containing lipoproteins was observed after simvastatin and atorvastatin treatment. In addition, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractional catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholesterol was lower in the atorvastatin and simvastatin groups. However, only atorvastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyltransferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified LDL transport and hepatic cholesterol metabolism differently.     

Streptozotocin- and Alloxan-Induced Diabetes Modifies Total Plasma and Lipoprotein Lipid Concentration and Composition without Altering Cholesteryl Ester Transfer Activity

Abstract: The objectives of this study were to determine the total plasma and lipoprotein lipid concentration and composition and cholesteryl ester transfer activity in two diabetic animal models (alloxan-induced diabetes in rabbits and streptozotocin-induced diabetes in rats). Furthermore, we wanted to determine if the severity of diabetes influences lipoprotein lipid profiles and cholesteryl ester transfer activity. Rats and rabbits were randomly divided into non-diabetic and diabetic groups. Rats were administered either 55 mg/kg or 100 mg/kg of streptozotocin intravenously through the tail vein, while rabbits were administered 100 mg/kg or 200 mg/kg of alloxan intravenously through the marginal ear vein under light anesthesia. Hyperglycaemia was tested for at 48 hr following the doses. Total and lipoprotein cholesterol and triglyceride concentrations using enzymatic kits and cholesteryl ester transfer activity from low-density lipoproteins to high-density lipoproteins using ³H-cholesteryl ester incorporated into low-density lipoproteins were determined. Elevations in both total and lipoprotein cholesterol and triglyceride concentrations and alterations in lipoprotein lipid composition are observed following the onset of drug-induced diabetes in rats and rabbits compared to non-diabetics. However, these findings were observed only in animals administered the higher streptozotocin and alloxan dose. Furthermore, cholesteryl ester transfer from low-density lipoproteins to high-density lipoproteins is not significantly different in drug-induced diabetic compared to non-diabetic rats and rabbits, regardless of which streptozotocin and alloxan dose was used. These findings suggest that difference in lipoprotein lipid concentration and composition as a result of drug-induced diabetes is independent of cholesteryl ester transfer activity in both rats and rabbits. Furthermore, diabetic severity may influence lipoprotein metabolism in these animal models.     

Effects of gemfibrozil treatment on vascular reactivity of streptozotocin-diabetic rat aorta

The effects of gemfibrozil treatment on plasma lipids, lipid peroxides and vascular reactivity of aorta were investigated in diabetic rats. Rats were divided randomly into two groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of streptozotocin (45 mg kg(-1)). Twelve weeks after the induction of diabetes, some of the control and diabetic rats were started treatment with gemfibrozil (100 mg kg(-1) daily; gavage) for 2 weeks. Blood glucose, plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol and thiobarbituric acid reactive substances (TBARS) levels were markedly increased and gemfibrozil treatment restored these parameters in diabetic rats. However high-density lipoprotein (HDL) cholesterol levels did not differ in all experimental groups. In diabetic rats, the endothelium-dependent relaxations to acetylcholine were decreased when compared with control rats. Gemfibrozil treatment restored the endothelium-dependent responses to acetylcholine in diabetic rats. The endothelium-independent relaxation responses to sodium nitroprusside were not altered in all groups. These findings suggest that gemfibrozil treatment has beneficial effects against cardiovascular and metabolic complications of diabetes via its hypolipidaemic and antioxidant properties.     

栗酮对动脉粥样硬化大鼠的治疗作用

目的：观察栗酮对动脉粥样硬化大鼠的治疗作用。方法：采用高脂饲料喂养的方法诱发大鼠动脉粥样硬化模型。造模8周后,选取造模成功大鼠50只随机分为栗酮300、150、75mg/kg剂量组、阳性组（非诺贝特）、模型对照组,每组10只,连续灌胃给药60d,模型对照组给予等体积的蒸馏水,给药同时仍采取高脂饲料喂养。另取10只大鼠为正常对照组,灌胃给予蒸馏水,正常饲料喂养。60d后分别采血检测血清总胆固醇（CHOL）、TG、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、氧化型低密度脂蛋白（Ox-LDL）及取胸主动脉内皮细胞观察细胞凋亡情况,同时取主动脉作病理形态学观察。结果：大鼠连续给栗酮（300mg/kg、150mg/kg）60d血清CHOL、TG、LDL-C、Ox-LDL、细胞凋亡比率较模型对照组明显减低（P〈0.05）,300mg/kg、150mg/kg剂量组大鼠主动脉壁泡沫细胞数目及弹性纤维损伤等病变明显较高脂模型组减轻。结论：栗酮具有明显的降脂及抗动脉壁损伤的作用。     

Hyperbaric oxygen therapy does not potentiate doxorubicin-induced cardiotoxicity in rats

The present study was designed to investigate the protective effect of rosuvastatin on methionine-induced hyperhomocysteinaemia and haematological changes in albino rats. Methionine (1 g/kg, orally) administration to pathogenic control rats (i.e. group II) for 30 days significantly (P < 0.01) increased the levels of homocysteine, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) and decreased the levels of high-density lipoprotein cholesterol (HDL-C) in serum. Haematological observations of the peripheral blood smears of pathogenic rats (i.e. group II) fed with methionine also showed crenation of red blood cells cell membrane and significant (P < 0.01) increase in total leucocyte count, differential leucocyte count and platelet counts with significant (P < 0.01) decrease in the mean haemoglobin levels as compared to vehicle control rats (group I). Administration of rosuvastatin (0.5 mg/kg/day, orally) to hyperhomocysteinaemic rats for 30 days significantly (P < 0.01) decreased the levels of homocysteine, TC, TGs, LDL-C, VLDL-C and increased the levels of HDL-C in serum. The present results provide clear evidence that oral treatment with rosuvastatin produces homocysteine and lipid lowering activity and also reversal of haematological changes induced by methionine in rats.     

Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study

ABSTRACT

Objectives: To assess the long-term safety and tolerability and to further evaluate the effect of ezetimibe plus simvastatin on LDL-C, HDL-C, and triglyceride levels in subjects with primary hypercholesterolemia.

Methods: This was a 12-month, double-blind, placebo-controlled extension study that enrolled patients with primary hypercholesterolemia who had successfully completed the 12-week, double-blind, placebo-controlled trial of ezetimibe coadministered with simvastatin. The initial dose administered to patients in the extension was ezetimibe 10 mg coadministered with simvastatin 10 mg with the option to up-titrate statin dosage if LDL-C goals were not met. Safety and tolerability were assessed through clinical and laboratory adverse experiences (AEs). Changes from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels were measured.

Results: Overall, 87 patients were randomized to receive ezetimibe + simvastatin and 22 were randomized to receive simvastatin and placebo. Treatment-emergent AEs were reported for 72/87 (83%) ezetimibe + simvastatin-treated patients and for 17/22 (77%) simvastatin-treated patients. The most commonly reported AEs in the simvastatin treatment group were hypertension, gastro-esophageal reflux, and musculoskeletal pain (each reported by 3/22 [14%] patients); and in the ezetimibe + simvastatin group were upper respiratory tract infection (16/87 [18%]), arthralgia and musculoskeletal pain (both reported by 10/87 [11%] patients). Drug-related AEs were reported for 3/22 (14%) simvastatin-treated patients and 21/87 (24%) patients in the coadministration group. AEs considered serious by the investigator were reported by 2/22 (9%) patients taking simvastatin monotherapy and by 20/87 (23%) patients taking ezetimibe + simvastatin. Discontinuations due to AEs occurred in no patients taking simvastatin monotherapy and in 7/87 (8%) patients taking ezetimibe + simvastatin. Percent change ± standard deviation from baseline in LDL-C was ?29% ± 15.4 and ?44% ± 14.2 in subjects taking simvastatin monotherapy and ezetimibe + simvastatin, respectively.

Conclusions: Ezetimibe coadministered with simvastatin was generally well-tolerated and no new safety concerns were raised. Both treatments effectively maintained improvements in lipid parameters throughout the course of the studies. Interpretation of these results was limited by the small convenience sample included in the trial.     

SIPI-7623与辛伐他汀联合用药对高脂血症大鼠的降血脂作用

目的探讨SIPI-7623与辛伐他汀联合用药对高脂血症大鼠的降血脂作用。方法所有大鼠分为空白组、模型组、SIPI-7623低剂量组(20 mg/kg)、SIPI-7623中剂量组(40 mg/kg)、SIPI-7623高剂量组(80 mg/kg)、辛伐他汀低剂量组(5 mg/kg)、辛伐他汀高剂量组(10 mg/kg)、联合给药低剂量组(SIPI-762320 mg/kg+辛伐他汀5 mg/kg)及联合给药高剂量组(SIPI-762340 mg/kg+辛伐他汀5 mg/kg),每组6只。除空白组外,其他各组大鼠均按体质量给予脂肪乳剂灌胃造模。造模成功后分别给予相应干预药物。连续给药21 d后测定大鼠血脂指标,包括总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(lowdensity lipoprotein cholesterol,LDL-C),并计算相应抑制率。处死大鼠后取肝脏进行苏木精-伊红染色切片并在镜下观察病理变化情况。测定大鼠谷丙转氨酶(alanine aminotransferase,AST)、谷草转氨酶(aspartate aminotransferase,AST)、肌酸激酶(creatine kinase,CK)及肌酸激酶同工酶(CK-MB)以观察安全性。结果SIPI-7623各剂量组、联合给药各剂量组及辛伐他汀高剂量组大鼠TC、TG及LDL-C水平低于模型组(P<0.05或P<0.01)。SIPI-7623低、中及高剂量组对TC的抑制率分别为41.34%、42.61%和46.30%,对TG的抑制率分别为53.06%、56.12%和68.37%,对LDL-C的抑制率分别为46.84%、46.84%和56.98%。联合给药低剂量组及高剂量组对TC的抑制率分别为53.35%和52.23%,对TG的抑制率分别为63.27%和65.30%,对LDL-C的抑制率分别为65.05%和61.67%。辛伐他汀高剂量组对TC、TG及LDL-C的抑制率分别为39.26%、53.06%和42.43%。各组间大鼠ALT、AST、CK及CK-MB差异均无统计学意义(P>0.05)。病理观察结果显示,联合给药各剂量组和SIPI-7623中、高剂量组大鼠肝脏病理变化情况优于其他各组。结论SIPI-7623具有降低血脂的作用,且与辛伐他汀联用效果优于单独使用SIPI-7623和辛伐他汀。     

Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus

Aim: The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin monotherapy on lipid profile, lipoprotein(a) (Lp(a)) and apoprotein(a) (Apo(a)) levels in type II diabetic patients. Patients/methods: In this double-blind, randomized clinical trial, 75 patients were assigned to one of two treatment groups for 4 months. Group A received simvastatin monotherapy; group B received L-carnitine and simvastatin. The following variables were assessed at baseline, after washout and at 1, 2, 3 and 4 months of treatment: body mass index, fasting plasma glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, Apolipoprotein A1, Apo B, lipoprotein(a) and apoprotein(a). Results: At the end of treatment in the carnitine and simvastatin combined group compared with the simvastatin alone group, we observed a significant decrease in glycemia (p < 0.001), tryglicerides (p < 0.001), Apo B (p < 0.05), Lp(a) (p < 0.05), apo(a) (p < 0.05), while HDL significantly increased (p < 0.05). Conclusions: The coadministration of carnitine and simvastatin resulted in a significant reduction in Lp(a) and apo(a) and may represent a new therapeutic option in reducing plasma Lp(a) levels, LDL cholesterol and Apo B100.     

Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes

Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7–9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.     

大黄联合辛伐他汀治疗对维持性血液透析患者全身微炎症状态的影响分析

目的通过与空白对照组和单纯应用辛伐他汀组对比,探究大黄联合辛伐他汀治疗对维持性血液透析患者全身微炎症状态的影响。方法选取50例需要维持性血液透析的患者,随机分成3组,分别为空白对照组、辛伐他汀组和大黄联合辛伐他汀组,比较3组治疗前后的全身微炎症状态指标。结果两试验组患者治疗后的白蛋白和高密度脂蛋白胆固醇与治疗前相比有明显升高,其他各项指标与治疗前相比均有明显下降;两试验组患者治疗后的白蛋白和高密度脂蛋白胆固醇与对照组相比明显增高,而其他各项指标与对照组相比均有明显降低;两试验组治疗后比较,大黄联合辛伐他汀组治疗后白蛋白和高密度脂蛋白胆固醇较辛伐他汀组明显增高,而其他各项指标除三酰甘油外,与辛伐他汀组相比均有明显降低。结论大黄和辛伐他汀均具有良好的抗炎作用,但二者联合应用可以更加有效的治疗维持性血液透析患者的全身微炎症状态。     

Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis

This study was conducted to investigate the hypocholesterolemic effect of the hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis in a 5 l fermenter. The composition of HW was mainly carbohydrate (83.9%) and protein (11.8%) on a dry basis, and the carbohydrate of HW consisted of glucose, mannose, galactose, and arabinose in the molecular ratio of 1.0 : 0.8 : 0.5 : 0.1, respectively. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet, body and liver weights were not significantly different from those of the controls. The serum total cholesterol (TC) of all mice groups administered HW (150 and 300 mg/kg/d, respectively) with the cholesterol-enriched diet decreased more than in the control group. Among the mice fed the cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL) cholesterol level, but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL- and VLDL+LDL-cholesterol levels consequently decreased the atherogenic value. The results indicate that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol level. The 300 mg/kg dose had a significant effect on the serum TC level.     

Effect of olive leaves extract on the antidiabetic effect of glyburide for possible herb-drug interaction

The concomitant use of olive leaves (OL) and glyburide (GLB) is a possible therapy for diabetic patients. However, there is no report about the effect of OL on the antidiabetic effect of GLB till now. In the current study, the possible interaction of olive leaves extract (OLE) with GLB was assessed to determine if there was any pharmacological benefit over GLB alone. Seven groups of male Sprague Dawley rats were used. Normal rats of the 1st group treated with 2 mL/kg of 3% Tween 80 (vehicle). The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), OLE low dose and OLE high dose respectively, while the 6th–7th groups administered combinations of GLB plus OLE low dose and GLB plus OLE high dose, respectively. All treatments were administered orally once daily for 8 weeks.The use of GLB+OLE-500 obviously improved fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c) in diabetic rats (95.5 ± 5.55 mg/dL, 6.8 ± 0.16 mg/dL and 6.1 ± 0.29%, respectively) compared to those treated with GLB monotherapy (140.0 ± 6.36 mg/dL, 5.4 ± 0.19 mg/dL and 7.0 ± 0.20%, respectively). The lipid profile [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] was significantly improved in diabetic rats exposed to GLB+OLE-500 (35.6 ± 1.51 mg/dL, 48.5 ± 2.74 mg/dL, 25.1 ± 1.21 mg/dL and 17.0 ± 0.82 mg/dL, respectively) in comparison with diabetic group exposed to GLB alone (43.2 ± 2.15 mg/dL, 56.8 ± 2.14 mg/dL, 18.6 ± 0.96 mg/dL, 23.0 ± 1.26 mg/dL, respectively). Additionally, the benefit impacts of GLB+OLE-500GLB+OLE-500 therapy on the antioxidant and lipid peroxidation parameters in the pancreatic tissues of diabetic rats were higher than those of GLB monotherapy. Moreover, GLB plus OLE-500 combination had the greatest effect on restoration of the insulin content of Beta (β) cells and reduction of the glucagon and somatostatin of Alpha (α) and Delta (δ) endocrine cells in the pancreatic islets among the different treatment. The current study suggests that OL and GLB combination could cause herb-drug interactions through modulation of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes expression in the liver of diabetic rats.     

Antidiabetic effect of Punica granatum flowers: Effect on hyperlipidemia,pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes

The present study investigated the effects of Punica granatum aqueous extract (PgAq) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, lipid profiles (atherogenic index), lipid peroxidation (LPO) and activities of both non-enzymatic and enzymatic antioxidants. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg) to albino Wistar rats. The increase in blood glucose level, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), LPO level with decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH) content and antioxidant enzymes namely, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of PgAq at doses of 250 mg/kg and 500 mg/kg for 21 days resulted in a significant reduction in fasting blood glucose, TC, TG, LDL-C, VLDL-C and tissue LPO levels coupled with elevation of HDL-C, GSH content and antioxidant enzymes in comparison with diabetic control group.     

Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2, FKBP12.6, and SERCA2a in rats

Aim:

To study whether calcium-modulating proteins CASQ2, FKBP12.6 and SERCA2a participate in diabetic cardiomyopathy, and whether the beneficial actions of testosterone, sildenafil or fructose diphosphate Sr (FDP-Sr) in the treatment of diabetic cardiomyopathy result from suppressing these molecules.

Methods:

Fifty male Sprague-Dawley (SD) rats were divided into five groups. Except for the normal group (non-diabetic), the other four groups were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes. Four weeks after STZ injection, the four groups received sildenafil (12 mg·kg^-1·d^-1, ig, for 4 week), FDP-Sr (200 mg/kg, ig, for 4 week), testosterone propionate (4 mg·kg^-1·d^-1, sc, for 4 week), or no treatment, respectively.

Results:

In the diabetic rats, blood glucose, free fatty acids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) were significantly increased, while high-density lipoprotein cholesterol (HDL-C) was significantly reduced, as compared to the non-diabetic rats. Cardiac dysfunction and myocardial hypertrophy of the diabetic rats were associated with increased mRNA and protein expression of iNOS, OBRb, and PKCɛ, while expression of CASQ2, SERCA2a, and FKBP12.6 was significantly down-regulated. Sildenafil and FDP-Sr, but not testosterone, significantly attenuated the biomarker abnormalities, without changing the metabolic abnormalities.

Conclusion:

CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy. Sildenafil and FDP-Sr, but not testosterone, attenuated the cardiac dysfunction in diabetic cardiomyopathy, without changing the metabolic abnormalities, which may results from inhibiting oxidative and inflammatory cytokines and improving calcium homeostasis.     

瑞舒伐他汀纠正早期糖尿病肾病并发高脂血症患者的血脂代谢紊乱的临床研究

目的:探讨瑞舒伐他汀纠正早期糖尿病肾病并发高脂血症患者的血脂代谢紊乱的疗效及安全性。方法:选择门诊及住院的早期糖尿病肾病并发高脂血症患者104例,随机分为对照组36例、瑞舒伐他汀10mg.d-1组33例和20mg.d-1组35例。3组治疗6个月后,比较总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿白蛋白排泄率(UAER)、血浆肌酐(Scr)和C反应蛋白(CRP)的变化。结果:瑞舒伐他汀治疗6个月后,10mg.d-1组和20mg.d-1组患者TC、TG、LDL-C、CRP水平均明显降低,HDL-C升高,差异有统计学意义(P<0.05);20mg.d-1组LDL-C降低更为明显,但差异无统计学意义(P>0.05);UAER、Scr水平治疗前、后无明显变化,差异无统计学意义(P>0.05)。结论:瑞舒伐他汀10mg.d-1和20mg.d-1均可明显降低早期糖尿病肾病并发高脂血症患者TC、TG、LDL-C、CRP水平,升高HDL-C,显著降脂,而对肾功能无不良影响。     

Contractile responses in spontaneously diabetic mice. II. Effect of cholestyramine on enhanced contractile response of aorta to norepinephrine in C57BL/KsJ (db/db) mice

To examine the possible role of low-density lipoprotein (LDL) cholesterol in the enhanced norepinephrine (NE)-induced contractile response seen in spontaneously diabetic mice (db/db mice), we examined the effect of chronic administration of cholestyramine on the NE-induced contraction. Although chronic cholestyramine (300 mg/kg, po for 1 month) significantly lowered total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglyceride, the plasma glucose and insulin levels were unaffected. The enhanced NE response in diabetic mice was not affected by the chronic administration of cholestyramine. The K(+)-induced contractile response was not different among nondiabetic, diabetic, and diabetic mice chronically treated with cholestyramine. These results suggest that neither LDL cholesterol nor triglyceride is involved in the enhancement of the NE-induced contractile response seen in spontaneously diabetic mice.     

Antihyperlipidaemic activity of swertiamarin,a secoiridoid glycoside in poloxamer-407-induced hyperlipidaemic rats

We have investigated antihyperlipidaemic effect of swertiamarin (50 mg/kg, oral once) isolated from the perennial herb Enicostemma littorale Blume in poloxamer 407 (P-407)-induced hyperlipidaemic rats. Rats were made hyperlipidaemic by intraperitoneal administration of P-407 (400 mg/kg). Serum lipid levels such as total cholesterol, triglycerides and low-density lipoprotein cholesterol increased significantly (P < 0.001) compared with normal control rats. All these changes were significantly prevented in the rats treated with swertiamarin. Serum high-density lipoprotein (HDL) cholesterol was found to be reduced in the P-407 control rats. However, administration of swertiamarin significantly (P < 0.01) increased HDL levels and it showed a significant lipid-lowering effect, as well as a high antiatherogenic potential. Overall swertiamarin is an effective lipid-lowering lead compound and can be useful for preventing atherosclerosis.     

油酰乙醇胺对高脂血症大鼠降血脂及肝脏的保护作用

目的观察油酰乙醇胺(OEA)对高脂血症模型大鼠降血脂及肝脏保护作用。方法高脂饮食建立高脂血症大鼠模型,分别观察OEA(10,203,0 mg/kg)对高脂血症大鼠的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)、肝重和肝脏系数、肝脏丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的影响。制作冰冻切片观察大鼠肝脏脂质变性程度。结果与模型组相比,OEA(20,30mg/kg)具有降血脂作用,同时降低血清ALT、肝脏脂质、肝重和肝脏系数、肝脏MDA水平,升高肝脏GSH-Px活力。结论 OEA能降低高脂血症大鼠血脂、抑制肝脏脂肪沉积,并减轻脂质过氧化物对肝脏的损伤。     

Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats

Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we found the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and several inflammatory markers including interleukin (IL)-8, IL-6, C-reaction protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 significantly elevated, while those of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) decreased. Moreover, mRNA expressions of ROCK and nuclear factor-kappa B (NF-κB) and activity of ROCK in thoracic aorta were greatly up-regulated. Remarkably, administrating fasudil (10, 30 mg/kg per day) or simvastatin (10 mg/kg per day) to hypercholesterolemic rats for 2 weeks, activation of ROCK and NF-κB in thoracic aorta were suppressed, status of dyslipidemia were improved and inflammatory markers lowered. From the histopathological examination, fasudil treatment was found to lessen the thickening noted in the aortic intima and media of the hypercholesterolemic rats. These results suggested fasudil-induced inhibition of ROCK may improve lipid metabolism and has anti-inflammatory effect, which might expand the clinical application of fasudil as a new therapy for hypercholesterolemia and preventing the development of atherosclerosis.     

Myrtenal alleviates hyperglycaemia,hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Context: Myrtenal is monoterpene a constituent of essential oils found mainly in herbs such as mint, pepper, cumin, etc. It exerts admirable pharmacological activities against many diseases including diabetes. Hyperlipidaemia is a secondary complication of diabetes and also a major risk factor for cardiovascular diseases.

Objective: The present study investigated the possible antihyperlipidaemic efficacy of myrtenal on plasma glucose, pancreatic insulin, plasma and tissue lipid levels in streptozotocin (STZ) induced diabetic rats.

Materials and methods: Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40?mg/kg b.w.). Myrtenal (80?mg/kg) was administered orally to diabetic rats for a period of 28 d. Plasma glucose, pancreatic insulin, TC, TGs, FFAs, PLs, LDL-C, HDL-C, VLDL, atherogenic index, (HMG-CoA) reductase, LPL, LCAT and liver histology were analyzed.

Results: Diabetic rats showed significantly (p?<?0.05) increased plasma glucose (273.18?mg/dL), total cholesterol (142?mg/dL), triglycerides (126?mg/dL), free fatty acids (118?mg/dL), phospholipids (153?mg/dL), low-density lipoprotein (88.07?mg/dL), very low-density lipoprotein (25.2?mg/dL), atherogenic index, whereas a decrease in the levels of pancreatic insulin (97.48?ng/mg) and high-density lipoprotein (29.12?mg/dL). In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase (0.94 HMG-CoA ratio/(mevalonate) increased significantly in contrast to the activities of lipoprotein lipase (4.87 μmoles of glycerol liberated/h/L) and lecithin cholesterol acyltransferase (54.61 μmoles of cholesterol esterified/h/L) in diabetic rats. Treatment with myrtenal significantly (p?<?0.05) improved the levels of plasma glucose, pancreatic insulin and lipid profiles. Moreover, the histopathological analysis of liver was also in agreement with the biochemical findings.

Discussion and conclusions: The present study indicates that myrtenal possess antihyperglycaemic and antihyperlipidemic properties, and could potentially be a useful phytochemical in treating diabetes.