Synthesis and Hypolipidemic Activity of 3-Imino-l-oxoisoindolines in Rodents

A series of substituted 3-imino-l-oxoisoindolines derivatives demonstrated significant hypolipidemic activity, lowering both serum cholesterol and triglycerides levels after 16 days of dosing at 20 mg/kg/ day ip in CF₁ mice. 2-Butyl-3-butylimino-l-oxoisoindoline lowered serum cholesterol levels 52% and serum triglyceride 42%. 2-Pentyl-3-imino-l-oxoisoindoline lowered serum cholesterol levels 42% and serum triglyceride 61%. These derivatives resulted in better activity than the parent compound, 3-imino-1-oxoisoindoline. These studies showed that compounds with N-alkyl substitution of nitrogen atoms in the ring and outside the ring possessed potent hypolipidemic activity at the low dose of 20 mg/kg/day ip in normolipidemic CF₁ mice. Studies with 2-butyl-3-butylimino-l-oxoisoinodine in rats showed that serum cholesterol was reduced 60% and serum triglyceride 43% after 14 days of dosing at 20 mg/kg/day, orally. Treatment with this agent lowered lipid levels in the liver and aorta tissue, with increases in lipid levels in the small intestine tissue. Higher levels of cholesterol and phospholipids were excreted in the feces of treated animals compared to the control. Cholesterol levels of the very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions were reduced, whereas the HDL cholesterol levels were elevated significantly. This ratio of low-density lipoprotein (LDL) cholesterol:HDL cholesterol levels suggests that the agent may be effective in treating hyperlipidemic states in humans.     

Hypolipidemic Effects of 2-Furoic Acid in Sprague-Dawley Rats

2-Furoic acid was shown to be effective in lowering both serum cholesterol and serum triglyceride levels significantly in rats with an elevation of HDL cholesterol level at 20 mg/kg/day orally. LDL receptor activity was reduced in hepatocytes, aorta foam cells, small intestinal epithelium cells and fibroblasts. HDL receptor activity was elevated in the rat hepatocytes and small intestinal cells. These activities were correlated with inhibition of acyl CoA cholesterol acyl transferase activity. Neutral cholesterol ester hydrolase activity was elevated in rat hepatocytes and human fibroblasts. Thus, 2-furoic acid appears to interfere directly with activity of intracellular enzymes rather than affecting high affinity-mediated lipoprotein membrane receptors. In vivo treatment with 2-furoic acid led to reduction in the liver and small intestine ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn-glycerol 3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin induced lipoprotein lipase activities. 2-Furoic acid reduced biliary cholesterol levels but the agent increased bile salts which are lithogenic. Acute toxicity studies in mice suggest that the agent has some hepatic toxicity effects. The LD⁵⁰ was relatively low at 250 mg/kg IP in mice.     

Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats

Oral administration of a calcium antagonist, nicardipine hydrochloride (simply designated as nicardipine), in doses of 10-100 mg/kg tended to decrease total serum cholesterol and to increase high density lipoprotein (HDL) cholesterol in the normal rat. These effects of nicardipine were much greater than those of clofibrate, a standard cholesterol-lowering drug. Neither nicardipine nor clofibrate caused significant alteration in serum triglyceride and phospholipid. In hypercholesterolemic rats, nicardipine increased significantly HDL cholesterol with a reduction of total serum cholesterol, whereas clofibrate did not change HDL cholesterol. Separation of serum lipoproteins either by ultracentrifugation in various densities of KBr-NaCl solution or by polyacrylamide gel electrophoresis demonstrated that nicardipine increased preferentially HDL2 (density: 1.063-1.125), with a reduction of the low density lipoprotein (LDL) (density: 1.006-1.063) level in hypercholesterolemic rats. Serum triglyceride and liver phospholipid were increased slightly by nicardipine with no clear dose-dependency. Clofibrate also increased serum triglyceride. In normal rats, neither nicardipine nor nicotinic acid inhibited sterol biosynthesis from [1-14C]acetate in the liver, whereas clofibrate inhibited sterol production. Oral administration of [4-14C]cholesterol to hypercholesterolemic rats indicated that nicardipine had no inhibitory effect on the intestinal absorption of cholesterol.     

Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats

Recently, we found that 4-hydroxyderricin, one of the major chalcones in Angelica keiskei extract (an ethyl acetate extract from the yellow liquid of stems), suppressed increases in systolic blood pressure and reduced both serum very low-density lipoprotein levels and liver triglyceride content in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, we have isolated laserpitin, a characteristic coumarin, from the A. keiskei extract and examined the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP. Six-week-old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks with free access to the diet and water. Bodyweight gain was reduced by dietary laserpitin after 4 weeks through to 7 weeks without any significant change in daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo) E levels were significantly increased, which was due to significant increases in cholesterol, phospholipid and apoE contents in the low- and high-density lipoprotein (LDL and HDL, respectively) fractions. These results suggest that dietary laserpitin increases serum apoE-HDL levels. In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with laserpitin for 7 weeks. An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in hepatic triglyceride lipase may be responsible for the increase in serum HDL levels and also indicated that a marked decrease in adipocyte determination and differentiation factor 1 may be responsible, at least in part, for the decrease in hepatic triglyceride content. In conclusion, dietary laserpitin produces increases in serum HDL levels, especially apoE-HDL, and decreases in the hepatic triglyceride content in SHRSP.     

The Effects of N(4-Methylphenyl)diphenimide on Lipid Metabolism of Sprague Dawley Rats

N(4-Methylphenyl)diphenimide proved to be an effective hypolipidemic agent in rats at 10 and 20 mg/kg/day. Both serum cholesterol and triglyceride levels were reduced significantly. Decreases in tissue lipids as well as VLDL cholesterol levels were observed. HDL-cholesterol was elevated even at 10 mg/kg/day. The agent was equally effective in hyperlipidemic diet-induced rats, lowering serum lipids and VLDL- and LDL-cholesterol while elevating HDL-cholesterol levels. The drug interfered with the incorporation of ³H-cholesterol and ³H-palmitic acid into chylomicrons, VLDL, and LDL. The two precursors were incorporated at a higher rate into HDL.³H-Leucine was incorporated into chylomicrons, VLDL, and LDL at a higher rate, but not into HDL. Reduced uptake of the precursor for lipid synthesis was noted in tissues after treatment with the drug.     

Hypolipidemic Activity of 3-Amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones in Rodents

A series of 3-amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones were synthesized and shown to be effective in lowering both serum cholesterol and triglyceride levels significantly in CF₁ mice and Sprague-Dawley rats. All analogs showed better activity than the standard drugs, lovastatin and clofibrate, in reducing the serum cholesterol and triglyceride levels in mice at 8 mg/kg/day intraperitoneally. The best active analogs, 3-morpholino-1-(3-nitrophenyl)propan-1-one ( 4 ) and 3-piperidino-1-(3-nitrophenyl)propan-1-one ( 5 ), exhibited 58% and 67% reduction of serum cholesterol levels, respectively, and 42% and 46% reduction of serum triglyceride levels, respectively, after 16 days of administration at 8 mg/kg/day intraperitoneally in CF₁ mice. In Sprague-Dawley rats at 8 mg/kg/day oral administration, both compounds ( 4 and 5 ) significantly decreased the serum cholesterol and triglyceride levels. Rat tissue lipid levels were reduced significantly by compound 4, while less effects resulted from compound 5. The cholesterol and triglyceride levels in chylomicrons, VLDL, and LDL fractions were reduced by both analogs while the HDL cholesterol levels were significantly increased. Compound 5 was also effective in lowering serum cholesterol and triglyceride levels in hyperlipidemic mice, at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day orally. Cholesterol and triglyceride lowering effects of the agents were correlated with inhibition of the activities of liver acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and lipoprotein lipase, and with elevation of the activity of cholesterol ester hydrolase.     

Hypolipidemic activity of trimethylamine-carbomethoxyborane and related derivatives in rodents

A number of substituted amine-carboxyborane esters were examined for their hypolipidemic activity in rodents. Trimethylamine-carbomethoxyborane, Me3NBH2C(O)OMe, was observed to be the most effective hypolipidemic agent in the rodent at the low dose of 8 mg/kg/d. This agent effectively increased the high density lipoprotein (HDL) cholesterol content and lowered the low density lipoprotein (LDL) cholesterol and triglyceride contents of rat lipoproteins. Furthermore, the agent accelerated cholesterol excretion from the body of the rat and reduced the activity of the rate-limiting enzyme involved in the de novo synthesis of lipids in the liver. The agent has a safe therapeutic index, and appeared to have more promise as a therapeutic agent than other borane esters.     

辛伐他汀对冠心病合并高血压患者尿蛋白的影响

目的探讨辛伐他汀对冠心病合并高血压患者尿蛋白的影响。方法选取内蒙古自治区人民医院2008年4月至2011年1月收治冠心病合并高血压患者110例,采用随机数字表法分为对照组和辛伐他汀组,每组各55例;分别给予安慰剂和辛伐他汀40mg／d,疗程均为6个月;比较两组患者治疗前后TG（甘油三酯）、TC（总胆固醇）、HDL—C（高密度脂蛋白）、LDL—C（低密度脂蛋白）、血肌酐（Cr）、24h尿微量白蛋白（UMA）、血清超敏C反应蛋白（hsCRP）及血压水平等。结果两组患者治疗前TG、TC、HDL—C、LDL～C、Cr、UMA及hsCRP水平组间比较无显著差异（P〉0．05）;治疗后两组患者TG、TC、HDL—C、LDL—C、Cr、UMA及hsCRP水平较治疗前均明显改善,且辛伐他汀组患者治疗后TG、TC、HDL—C、LDL—C、Cr、UMA及hsCRP水平明显优于对照组（P〈0．05）;同时两组患者治疗前后收缩压、舒张压水平比较差异无统计学意义（P〉0．05）。结论辛伐他汀能够有效改善冠心病合并高血压患者尿蛋白水平,可用于早期肾病临床治疗。     

Hypolipidemic Activity and Toxicity of 3-Methoxy-N,N′-diaminophthalamide in Rodents

3-Methoxy-N,N′-diaminophthalamide was observed to be a potent hypolipidemic agent in rodents. Serum cholesterol and triglyceride levels in rats were significantly reduced as were lipid contents of the liver, small intestine, and aorta wall. VLDL and LDL cholesterol levels were significantly reduced. Unfortunately, HDL cholesterol levels were also markedly reduced. Furthermore, acute toxicity studies showed that the compound caused marked increases in serum CP kinase activity with doses of 40 and 100 mg/kg/day in mice. This is not a property of the 2,3-dihydrophthalazine-1,4-dione, the resultant product of the N,N′-diaminophthalamides. Apparently, closing the ring results in a safer compound with elevations in HDL cholesterol levels, a desirable characteristic in effective hypolipidemic agents.     

普伐他汀治疗高脂血症及对血浆D-二聚体的影响

目的 :研究普伐他汀对高脂血症病人降脂作用及对血浆D 二聚体的影响。方法 :高脂血症病人 36例 ,服用普伐他汀 10mg·d- 1,服药 4wk后若血清TC >5.2mmol·L- 1,则剂量加倍 ,疗程 12wk。服药前后每 4wk测TC ,TG ,HDL C ,LDL C及D 二聚体。结果 :治疗 12wk ,普伐他汀降低TC ,TG的总有效率分别为 94 %和 59% ,升高HDL C的总有效率为 54%。治疗 12wk后TC ,TG ,LDL C ,D 二聚体分别下降 ( 2 6± 12 ) % ,( 2 4± 2 0 ) % ,( 2 7±18) % ,( 4 0± 17) % ,HDL C上升 ( 15± 3) % ,差异有非常显著意义 (P <0 .0 1)。结论 :普伐他汀能够降低TC ,TG和LDL C ,升高HDL C ,且能降低血浆D 二聚体水平 ,从而改善凝血、纤溶系统的紊乱     

Hypolipidemic activity of cyclic imido alkyl ethers, thioethers, sulfoxides, and sulfones

N-Substituted alkyl ethers, thioethers, sulfoxides, and sulfones of cyclic imides (e.g., phthalimide, saccharin, 1,8-naphthalimide, succinimide, and 2,3-dihydrophthalazine-1,4-dione) were shown to have potent hypolipidemic activity at doses of 10 and 20 mg/kg/d in rodents. These N-substitutions afforded no improvement over other known N-substitutions (e.g., butyl, 3-butanone, or the propionic acid derivatives of phthalimide, saccharin, and 2,3-dihydrophthalazine-1,4-dione) compared with the respective parent compounds. However, 2-(methoxyethyl)-1H-benz[de]isoquinoline-1,3-(2H)dione (3a), 2-[2-methylsulfinyl]ethyl-1H-benz[de]isoquinoline-1,3-(2H)dione (3c), 1-(2-methylsulfinyl)-2,5-pyrrolidenedione (4c), and 1-(2-methoxyethyl-2,5-pyrrolidenedione (4a) significantly improved activity compared with parent compounds, as well as previously reported N-substituted analogues, reducing serum cholesterol levels and serum triglyceride levels by 40%. The thioether of succinimide afforded a 54% reduction of serum cholesterol and a 41% reduction of serum triglyceride levels in mice after 16 d. The alkyl thioethers of 1,8-naphthalimide and succinimide significantly lowered cholesterol levels in serum VLDL and LDL, while the alkyl thioethers of succinimide elevated HDL cholesterol content. Tissue lipids were reduced in the liver and aorta by these selected derivatives. The activities of regulatory enzymes in de novo synthesis of hepatic cholesterol and triglyceride were inhibited by the selected 1,8-naphthalimide derivatives. In situ cholesterol and cholic acid reabsorption from intestines were suppressed by the presence of the agents.     

Novel agents for managing dyslipidaemia

An elevated low-density lipoprotein (LDL) cholesterol level is a strong predictor of coronary heart disease (CHD) risk. Over the past seven years, equally strong evidence has accumulated that lowering LDL cholesterol with HMG-CoA reductase inhibitors or statins reduces CHD risk and there is now widespread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholesterol reduction and whether, in people with very high levels, it would be preferable to achieve the LDL cholesterol goal with a powerful statin alone or combined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertriglyceridaemia. Already prevalent as a risk factor for CHD, this abnormality has been linked with insulin resistance, which is likely to increase greatly over the next decade, along with increasing obesity and diabetes. Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds. Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase. Future emphasis will be on correcting all lipid abnormalities for the prevention of CHD, not just lowering LDL cholesterol.     

Comparison of receptors and enzymes regulating cholesterol levels in liver between SHR/NDmcr-cp rats and normotensive Wistar Kyoto rats at ten weeks of age

The spontaneously hypertensive rat (SHR)/NDmcr-cp (SHR-cp), which is a metabolic syndrome model rat, was reported to show hypercholesteremia, as compared with lean littermates. The serum total cholesterol level in SHR-cp at 18 weeks of age is higher than that of normotensive Wistar Kyoto rat (WKY), but that in SHR-cp at 10 weeks of age is the same. The objective of this study is to clarify whether there are differences in the system regulating serum cholesterol levels between SHR-cp and WKY at 10 weeks of age. Total serum cholesterol levels, and cholesterol levels of high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) were similar in the two strains. However, the cholesterol levels in the liver of SHR-cp were lower than those of WKY. Next, mRNA levels of receptors (scavenger receptor class B type 1 [SRB1], LDL receptor [LDLR]) involved in uptake from serum to liver or enzymes of cholesterol catabolism (CYP7A1 and CYP8B1) and biosynthesis (mevalonate pyrophosphate decarboxylases [MPD]) in liver were compared between SHR-cp and WKY. High levels of MPD and LDLR and low levels of SRB1 were shown in SHR-cp, as compared with WKY. CYP7A1 and CYP8B1 levels were similar between SHR-cp and WKY. These results suggest that the serum cholesterol level in SHR-cp by the balance or regulation between the rise in cholesterol uptake and reduction in cholesterol biosynthesis in the liver is the same as that in WKY.     

Comparative studies on the influence of different fibrates on serum lipoproteins in endogenous hyperlipoproteinaemia

Summary Two trials have been performed in the same patients with hyperlipoproteinaemia Types IIb (12 cases), III (6 cases) and IV (11 cases). In the first study the lipid-lowering properties of bezafibrate, fenofibrate, gemfibrozil, etofibrate and etofylline clofibrate were compared and in a separate trial the influence of combined treatment with gemfibrozil plus colestipol and bezafibrate plus probucol on lipoproteins were investigated. The mean percentage lipid-lowering effect of each fibrate on serum and VLDL fraction was significant in the Types IIb, III and IV patients, but there were significant differences between the fibrates. In general, gemfibrozil and bezafibrate decreased plasma lipid levels more than etofibrate and etofylline clofibrate in Type IIb patients. In Type IV cases gemfibrozil and bezafibrate were significantly potent in reducing the triglyceride level than fenofibrate, etofibrate or etofylline clofibrate. All the fibrates produced an increase in HDL cholesterol, but there were significant differences between them were in the Type IV patients. The influence of fibrates on the LDL fraction was much more variable. In hyperlipoproteinaemia Type IIb, a decrease in both LDL cholesterol and LDL apolipoprotein B was observed. In Type III and IV patients, however, an increase in LDL concentration occurred. The addition of colestipol to gemfibrozil therapy led to a further decrease in total cholesterol, LDL cholesterol and LDL apolipoprotein B in Type IIb patients. In patients with hyperlipoproteinaemia Types III and IV colestipol prevented the increase in LDL concentration after treatment with gemfibrozil alone. The effect of probucol on LDL cholesterol was comparable to that of colestipol. Combined treatment with gemfibrozil and colestipol caused an increase in HDL cholesterol concentration in contrast to combined treatment with bezafibrate and probucol. It is concluded that combined therapy with fibrates plus bile acid sequestrant would be of practical value in patients with hyperlipoproteinaemia Types IIb, III and IV.     

Preventive effect of MK-733 (simvastatin), an inhibitor of HMG-CoA reductase, on hypercholesterolemia and atherosclerosis induced by cholesterol feeding in rabbits

MK-733 was found to prevent an increase of serum cholesterol levels in cholesterol-fed rabbits, and lovastatin also markedly inhibited their increase. MK-733 and lovastatin inhibited the increase of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, and it slightly affected the high density lipoprotein (HDL) cholesterol levels. MK-733 and lovastatin suppressed the increase of serum phospholipid levels and slightly affected the triglyceride levels. MK-733 suppressed the development of atherosclerosis in coronary arteries and aorta, and lovastatin also diminished their development.     

Long-term low-dose treatment with reserpine of cholesterol-fed rabbits reduces cholesterol in plasma,non-high density lipoproteins and arterial walls

The effects of long-term low-dose treatment with reserpine on plasma lipoproteins and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low-density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys; plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine at 43 microg/kg. d was continuously infused subcutaneously via implanted minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine (n = 4) significantly reduced the elevated levels of plasma total cholesterol and esterified and unesterified cholesterol throughout the study, and at 6 weeks of treatment these reductions were 42, 41, and 49%, respectively. The increased cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was reduced by 73% (p < 0.004) and 125I-tyramine cellobiose-labeled LDL by 67 to 86% (0.05 < p <0.004), respectively. The aortic intimal-medial thickness ratio was reduced by 70%. The decrease in elevated plasma total cholesterol was mainly due to cholesterol reductions in both LDL (41%) and non-high density lipoprotein (HDL) of density < 1.019 g/ml (51%). HDL cholesterol and triglyceride levels were unchanged. Reserpine had no significant effects on the clearance of 125I-tyramine cellobiose-LDL from plasma and there was a trend towards an increase in hepatic LDL receptor expression. Heart rate was decreased by 28%. There were no significant effects on blood pressure, liver and heart lipids, hematocrit, or plasma fibrinogen. The results suggest that treatment of cholesterol-fed rabbits with reserpine at a low dose over a long period prevents increases in plasma atherogenic lipoproteins. Reserpine decreases the cholesterol in aortic walls and the intima-media thickness ratio. This anti-atherosclerotic effect of reserpine may have therapeutic implication.     

Diabetic dyslipidaemia: current treatment recommendations

Insulin deficiency and hyperglycaemia in type 1 (insulin-dependent) diabetes mellitus produce lipid abnormalities, which can be corrected by appropriate insulin therapy. Diabetic nephropathy, which is the main risk factor for coronary heart disease (CHD) in type 1 diabetes, causes pro-atherosclerotic changes in lipid metabolism. Detection and treatment of elevated cholesterol levels is likely to be of benefit in these patients. Type 2 (noninsulin-dependent) diabetes mellitus is associated with abnormal lipid metabolism, even when glycaemic control is good and nephropathy absent. Elevated triglyceride levels, reduced high density lipoprotein (HDL) cholesterol and a preponderance of small, dense low density lipoprotein (LDL) particles are the key abnormalities that constitute diabetic dyslipidaemia. The prevalence of hypercholesterolaemia is the same as for the nondiabetic population, but the relative risk of CHD is greatly increased at every level of cholesterol. Based on effectiveness, tolerability and clinical trial results, treatment with HMG-CoA reductase inhibitors to lower LDL cholesterol is recommended as primary therapy. These agents are also moderately effective at reducing triglyceride and increasing HDL cholesterol levels. If hypertriglyceridaemia predominates, treatment with fibric acid derivatives is appropriate, although there is currently only limited clinical trial evidence that the risk of CHD will be reduced. In type 1 diabetes, but particularly in type 2 diabetes, lipid disorders are likely to contribute significantly to the increased risk of macrovascular complications. especially CHD. Management of the disordered lipid metabolism should be given a high priority in the clinical care of all patients with diabetes.     

微粒化非诺贝特与辛伐他汀治疗糖尿病合并高脂血症的比较

目的 :观察微粒化非诺贝特与辛伐他汀治疗 2型糖尿病 (NIDDM )合并高脂血症的疗效。方法 :4 0例 (男性 2 2例 ,女性 18例 ,年龄 55a±s 8a)NIDDM病人用微粒化非诺贝特胶囊 0 .2 g ,po ,qd× 8wk。另 38例 (男性 2 1例 ,女性 17例 ,年龄 54a± 9a)NIDDM病人用辛伐他汀片 5mg ,po ,qd× 8wk。结果 :非诺贝特组依次降低TC ,TG ,LDL C为18% ,4 6% ,2 2 %及升高HDL C 2 0 % ;辛伐他汀组依次下降 2 5% ,2 8% ,2 3%及升高 18%。非诺贝特组较辛伐他汀组TG下降更显著 (P <0 .0 1)。结论 :微粒化非诺贝特是NIDDM合并高脂血症病人有效的调脂药物 ,比辛伐他汀降低TG更有效     

旨可平软胶囊工艺改进前后调血脂药效对比研究

目的观察两种旨可平软胶囊内容物对高脂血症SD大鼠模型的调血脂作用。方法SD大鼠用高脂饲料喂养45 d,采血检测胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平,血脂升高达到试验要求后随机分组,分为模型对照组,旨可平Ⅰ低、中、高剂量组,旨可平Ⅱ低、中、高剂量组,并以采用标准饲料喂养试验动物设为空白对照组。在继续高脂饲料喂养的同时给予上述药物治疗15 d,再次采血检测上述血脂水平。结果高剂量旨可平Ⅰ可在一定程度上降低高脂大鼠TC水平;旨可平Ⅰ低、中、高3个剂量对高脂大鼠血清HDL均显示出不同程度的降低作用,且呈一定的量效关系,但仅在高剂量下对高脂大鼠血清LDL水平显示出一定的降低作用。旨可平Ⅱ低、中、高3个剂量对高脂大鼠血清TC与LDL水平显示出明显的降低作用,且具有量效关系。在各剂量水平下,与旨可平Ⅰ相比,旨可平Ⅱ对于高脂大鼠血清TC与LDL的降低作用更加显著;在低、中两个剂量水平下,旨可平Ⅱ较旨可平Ⅰ对于血清TC,TG,LDL 3项指标的降低作用更加显著,且中剂量旨可平Ⅱ可升高HDL水平。结论对高脂SD大鼠模型,旨可平Ⅰ和Ⅱ样品对血清TC与LDL均显示出较好的降低作用,但旨可平Ⅱ对HDL和TG的降低作用旨可平Ⅰ较弱。综合多种指标结果,旨可平Ⅱ较旨可平Ⅰ相比,其降脂作用强度较高。     

Hypolipidaemic activity in rodents of boron analogs of phosphonoacetates and cyanoborane adducts of dialkyl aminomethylphosphonates.

Boron analogues of phosphonoacetates proved to be potent hypolipidaemic agents in rodents, lowering both serum cholesterol and triglyceride levels. (C2H5O)3PBH2COOCH3 proved to be the most effective agent in mice, lowering serum cholesterol 46% and serum triglycerides 54% after 16 days. (C2H5O)3PBH2COOH and Na+H+(C2H5O)2(-O)PBH2COO- caused greater than a 40% reduction in lipids. The cyanoborane adducts of aminomethylphosphonates were generally less effective; (C6H5O)2P(O)CH2NH2BH2CN was the most effective, lowering serum cholesterol 32% and serum triglycerides 43% after 16 days. The phosphonoacetates appeared to lower lipid concentrations by several mechanisms. First, they lowered the de novo synthesis of cholesterol and triglycerides in the liver. Second, they accelerated the excretion of lipids into the bile and faeces. Thirdly, they modulated LDL and HDL-cholesterol contents in a manner which suggests they reduced the deposition of lipids in peripheral tissues, and accelerated the movement of cholesterol from tissues (e.g. plaques) to the liver for excretion into the bile.