Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent—monacolin K and antiinflammation agent—monascin

Monacolin K, an inhibitor for cholesterol synthesis, is the secondary metabolite of Monascus species. The formation of the secondary metabolites of the Monascus species is affected by cultivation environment and method. This research uses sweet potato (Ipomoea batatas), potato (Solanum tuberosum), casava (Manihot esculenta), and dioscorea (Dioscorea batatas) as the substrates and discusses the best substrate to produce monacolin K. The results show that Monascus purpureus NTU 301, with dioscorea as the substrate, can produce monacolin K at 2,584 mg kg⁻¹, which is 5.37 times to that resulted when rice is used as the substrate. In addition, more amount of yellow pigment can be found in Monascus-fermented dioscorea than in Monascus-fermented rice. The certain composition of yellow pigment is identified as monascin, which has been shown as an antiinflammation agent exhibiting potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice in previous studies. Therefore, dioscorea is concluded to be the best substrate for Monascus species to produce the cholesterol-lowering agent—monacolin K and antiinflammation agent—monascin.     

Improvement of monacolin K, γ-aminobutyric acid and citrinin production ratio as a function of environmental conditions of<Emphasis Type="Italic"> Monascus purpureus</Emphasis> NTU 601

Monascus, a traditional Chinese fermentation fungus, is used as a natural dietary supplement. Its metabolic products monacolin K and -aminobutyric acid (GABA) have each been proven to be a cholesterol-lowering drug and a hypotensive agent. Citrinin, another secondary metabolite, is toxic to humans, thus lowering the acceptability of red mold rice to the general public. In this study, the influence of different carbon and nitrogen sources, and fatty acid or oils, on the production of monacolin K, citrinin and GABA by Monascus purpureus NTU 601 was studied. When 0.5% ethanol was added to the culture medium, the production of citrinin decreased from 813 ppb to 561 ppb while monacolin K increased from 136 mg/kg to 383 mg/kg and GABA increased from 1,060 mg/kg to 7,453 mg/kg. In addition, response surface methodology was used to optimize culture conditions for monacolin K, citrinin and GABA production, and data were collected according to a three-factor (temperature, ethanol concentration and amount of water supplemented), three-level central composite design. When 500 g rice was used as a solid substrate with 120 ml water and 0.3% ethanol, the production of monacolin K at 30°C increased from 136 mg/kg to 530 mg/kg, GABA production increased from 1,060 mg/kg to 5,004 mg/kg and citrinin decreased from 813 ppb to 460 ppb.     

Production of the secondary metabolites γ-aminobutyric acid and monacolin K by <Emphasis Type="Italic">Monascus</Emphasis>

γ-Aminobutyric acid (GABA), a hypotensive agent, and monacolin K, a cholesterol-lowering drug, can be produced by Monascus spp. Under optimal culture conditions, the products of fermentation using Monascus spp. may serve as a multi-functional dietary supplement and can prevent heart disease. In this study, Monascus purpureus CCRC 31615, the strain with the highest amount of monacolin K, was identified from 16 strains using solid fermentation. Its GABA productivity was particularly high. Addition of sodium nitrate during solid-state fermentation of M. purpureus CCRC 31615 improved the productivity of monacolin K and GABA to 378 mg/kg and 1,267.6 mg/kg, respectively. GABA productivity increased further to 1,493.6 mg/kg when dipotassium hydrophosphate was added to the medium. Electronic Publication     

金黄地鼠高血脂模型的建立

目的建立高血脂金黄地鼠动物模型,研究红葡萄酒预防高血脂的作用。方法用含有2%胆固醇的高脂饲料喂养金黄地鼠,设正常对照组和模型组,饲养15 d。期间观察金黄地鼠对高脂饲料的耐受性,试验结束时,测量血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)值,并对肝脏进行光镜和电镜观察。结果金黄地鼠对高脂饲料具有较强的耐受性。经过15 d之后,模型组TC、TG、HDL-C、LDL-C、VLDL-C极显著升高(P<0.01),分别为对照组的9.06、4.19、2.43、6.21、18.88倍,而HDL-C/(LDL-C VLDL-C)显著降低(P<0.05),光镜和电镜观察表明模型组动物的肝脏出现脂肪肝样改变。结论本造型方法时间短,取血方便,血量充足,是一个较好的高血脂模型建立方法。     

Production of red mold rice using a modified Nagata type koji maker

In this research, a commercial koji maker with a rotary perforated bed of 5-m diameter was modified for red mold rice production. Monascus purpureus BCRC 31499 was selected for its high production capacities of monacolin K and red pigment. The selected strain was first cultivated in a 120-l submerged type fermentor at 34°C and 2 vvm aeration rate with 60 rpm agitation for 5 days using 20% liquefied rice porridge as carbon source. The high concentration red mold rice broth (>3.5 g/ml) was harvested for inocula and well mixed with cooked rice to an initial concentration of 2% v/w. The inoculated cooked rice then was directed into the modified koji maker, in which temperature and humidity profiles were kept at varied levels at different stages, respectively. Air was circulated to remove fermentation heat while the perforated bed rotated slowly for providing mild agitation. Lag phase of the Monascus sp. in the modified koji maker was determined to be 16 h by the time the koji temperature raised rapidly. Water was added into the koji bed by a water curtain at the 36th hour to keep the moisture content of the rice koji at 50% or above. At the final stage, temperature was adjusted to 34°C to direct red pigment production. After 7 days, 1,200-kg high quality red mold rice was harvested per batch. Labor costs, space, and fermentation time were reduced tremendously compared with those made by traditional methods.     

Monascus secondary metabolites: production and biological activity

The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.     

Development and production of cholesterol-lowering <Emphasis Type="Italic">Monascus</Emphasis>-nata complex

This study develops a new foodstuff, the Monascus-nata complex, which combines the functions of cholesterol-lowering monacolin k and bacterial dietary-fibre. Two Monascus strains, M. ruber and M. pilosus were fermented within cubical bacterial cellulose, nata de coco, obtained from Acetobacter fermented coconut juice, in a conditioned medium. The production levels and stability of monacolin k in the cultured Monascus-nata complex were determined to develop optimal fermentation conditions. The results indicated that a medium that comprised 5% glucose and 1.5% ammonium phosphate at pH 6.0–7.0 produced the most monacolin k (157 mg/l) for Monascus pilosus NCHU M-35. However, monosodium glutamate (MSG) and 0.001% ZnSO₄ inhibited the intracellular accumulation of monacolin k. Monacolin k within the Monascus-nata complex was relatively resistant to washing and changes of pH, but thermal processing and freezing storage markedly reduced the amount present. This novel Monascus-nata complex is potentially a healthy foodstuff.     

Effects of Apigenin on the Expression of LOX-1, Bcl-2, and Bax in Hyperlipidemia Rats

We aimed to investigate the impact of apigenin on LOX-1, Bcl-2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and the LOX-1 protein expression were apparently increased (P<0.01), while the high-density lipoprotein cholesterol (HDL-c) levels and the ratio of Bcl-2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL-c, and the LOX-1 protein expression were noticeably decreased (P<0.01), while the levels of HDL-c and the Bcl-2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low-dose, middle-dose, high-dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX-1 gene expression and increasing the Bcl-2/Bax ratio.     

The effects of Lactobacillus-fermented milk on lipid metabolism in hamsters fed on high-cholesterol diet

The objective of this study was to evaluate the effects of local Lactobacillus strains (NTU 101 and 102) on cholesterol-lowering effects in vivo. Thirty male hamsters were housed, divided into five groups, and fed on a cholesterol diet (5 g/kg diet) to induce hypercholesterolemia. Milk fermented by Lactobacillus paracasei subsp. paracasei NTU 101, Lactobacillus plantarum NTU 102, and Lactobacillus acidophilus BCRC 17010 was administrated for this study. After treatment with different fermented milk, blood was taken and liver was removed for the determination of lipoproteins, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride. Lactobacilli and bifidobacteria decreased (10⁵) in the control group; when hamsters were fed on fermented milk, the number of lactobacilli (10⁷–10⁸) and bifidobacteria (10⁵–10⁷) was increased. Serum and liver total cholesterol levels were significantly reduced by about 26.4, 23.5, and 30.1% and by about 17.7, 15.9, and 13.4% when hamsters were given fermented milk. However, serum HDL-C and LDL-C were also reduced. The results of this study showed that the hypocholesterolemic effect of local Lactobacillus strains was attributed to its ability to lower serum and liver total cholesterol levels. Thus, local Lactobacillus strains could significantly increase probiotic count.     

Citrinin-producing capacity of Monascus purpureus in response to low −frequency magnetic fields

Citrinin is a type of mycotoxin that negatively affects Monascus products. Application of a low-frequency magnetic field (LF-MF) decreased citrinin production by M. purpureus in liquid-state fermentation during shake flask culture. Under 30 °C incubation, six different magnetic field induction intensity (MF-II), four different exposure times and five exposure time periods were tested to discover optimal treatment conditions. The cultures were exposure to a MF-II of 1.6 mT from 0 to 2 d of incubation time. With LF-MF treatment, peak citrinin production decreased by 46.7% while yellow, red, orange pigments and monacolin K production increased by 31.3%, 40.3%, 41.7% and 29.3%, respectively, compared with control groups at 12 d of incubation. Moreover, the relative expression levels of the citrinin biosynthesis genes pksCT and ctnA were 0.46 and 0.43 times lower, respectively, than the control values relative to the GAPDH reference gene. This study provides evidence that LF-MF is a preferable way to alter M. purpureus metabolism to reduce citrinin production and to increase pigments and monacolin K production without affecting cell growth. Therefore, LF-MF may be used as a tool to process Monascus products to obtain important functional food additive while reducing the adverse effects of citrinin.     

The presence and the content of Monacolins in Red Yeast rice prepared from Thai glutinous rice

Red yeast rice which is a product of solid fermentation was prepared from several kinds of Thai glutinous rice (Oryza sativa L.) cv. Korkor 6 (RD6), Kam (Kam), and Sanpatong1 (SPT1). Monascus purpureus CMU001 isolated from available Chinese red yeast rice was used as the fermentation starter. The analysis for the presence and the content of monacolins, the cholesterol-lowering compounds, were carried out using high performance liquid chromatography (HPLC). The presence of the monacolins was confirmed by the retention time of the reference compounds and LC-MS. The results were compared to those obtained from the Chinese red yeast rice and Thai non-glutinous rice (O. sativa L. cv. Mali105). The chromatograms show the presence of monacolin K acid form (MKA), compactin (P1), monacolin M acid form (MMA), monacolin K (MK), monacolin M (MM), and dehydromonacolin K (DMK). A large peak of a compound with the molecular weight of 358 was also detected but could not be identified. The amount of two important monacolins, compactin, and monacolin K, were determined. It was found that the highest amount of compactin and monacolin K were 21.98 and 33.79 mg/g, respectively, when using Thai rice varity O. sativa L. cv. RD6 which was fermented without adding soybean milk.     

Antioxidant and hypolipidaemic properties of red seaweed,Gracilaria changii

The edible red seaweed, Gracilaria changii, was collected from the coastal area of Sarawak, Malaysia, and evaluated for its hypolipidaemic properties using high cholesterol/high fat (HF) induced male Sprague–Dawley rats. In the in vivo study, the HF diet group showed significantly higher total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), atherogenic index (AI) and body weight gain as compared to other treatment groups. At the end of treatment period, rats fed with a HF diet supplemented with 5 % freeze-dried G. changii powder had significantly reduced plasma TC (?39.19 %), LDL-C (?36.36 %), and triglycerides (TG) content (? 25.45 %). Meanwhile, 10 % seaweed powder significantly lowered the plasma TC, LDL-C and TG content by ?40.34, ?35.95 and ?30.91 % respectively, compared to the HF group. The AI of rats supplemented with 10 % seaweed powder was the lowest among the treatment groups and indicates a lowered risk for cardiovascular diseases. The plasma lipid peroxidation of the seaweed powder-fed groups was also significantly lower than the HF group, while the erythrocyte enzyme antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase of the treatment groups were also improved. Diets supplemented with seaweed powder also decreased plasma aspartate aminotransferase and the alanine aminotransferase levels.     

Statistical analysis and validation of process parameters influencing lovastatin production by Monascus purpureus MTCC 369 under solid-state fermentation

Monascus, a fermented rice (red mold rice), was found to reduce total cholesterol and triglyceride in serum due to the presence of lovastatin, a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor. Optimization and validation of different process parameters such as temperature, fermentation time, inoculum volume, and pH of the solid medium was done using Box-Behnken’s factorial design of response surface method for maximum production of lovastatin by Monascus purpureus MTCC 369. A maximum lovastatin production of 3.422 mg/g was predicted by day 14.43 of fermentation in a rice based solid medium of pH 6 when fermented at a temperature of 29.46°C, an inoculum volume of 5.11 mL, and using response surface plots and the point prediction tool of Design Expert 7.1.3 (Statease Inc., USA) software.     

成人原发肾病综合征病理类型与血脂代谢紊乱的关系

目的：研究成人原发肾病综合征(PNS)肾脏病理改变与血脂代谢紊乱的关系。方法：选取成人PNS患者109 例为研究对象, 分析不同病理类型PNS 患者血脂及血清脂蛋白代谢异常的发生率、代谢水平及胆固醇代谢异常的相关因素。结果：成人PNS 患 者血清总胆固醇(TC)升高、低密度脂蛋白胆固醇(LDL-C)升高、高密度脂蛋白胆固醇(HDL-C)降低、甘油三酯(TG)升高的发生率分 别为89.90%、69.72%、9.17%、41.28%,高胆固醇血症占51.37%,混合型高脂血症占39.45%;微小病变型肾病(MCD)、膜性肾病 (MN)、系膜增生性肾小球肾炎(MsPGN)、局灶阶段性肾小球硬化(FSGS)组间TC、TG、LDL-C、HDL-C 代谢异常发生率及代谢水平 比较均无明显差别(P>0.05);病理类型为MCD 及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋白定量呈正相关(r=0.440, P=0.036;r=0.361,P=0.001),与血白蛋白水平无明显相关性(P>0.05)。结论：成人PNS患者血脂代谢异常以TC 及LDL-C 升高为 主,临床分型中以高胆固醇血症及混合型高脂血症为主;病理类型为MCD及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋 白呈正相关,与血白蛋白水平无明显相关性。     

Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves

Oleuropein-rich extracts from olive leaves and their enzymatic and acid hydrolysates, respectively rich in oleuropein aglycone and hydroxytyrosol, were prepared under optimal conditions. The antioxidant activities of these extracts were examined by a series of models in vitro. In this study the lipid-lowering and the antioxidative activities of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts in rats fed a cholesterol-rich diet were tested. Wistar rats fed a standard laboratory diet or cholesterol-rich diets for 16 weeks were used. The serum lipid levels, the thiobarbituric acid reactive substances (TBARS) level, as indicator of lipid peroxidation, and the activities of liver antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) were examined. The cholesterol-rich diet induced hyperlipidemia resulting in the elevation of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C). Administration of polyphenol-rich olive leaf extracts significantly lowered the serum levels of TC, TG and LDL-C and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidneys and aorta decreased significantly after oral administration of polyphenol-rich olive leaf extracts compared with those of rats fed a cholesterol-rich diet. In addition, these extracts increased the serum antioxidant potential and the hepatic CAT and SOD activities. These results suggested that the hypocholesterolemic effect of oleuropein, oleuropein aglycone and hydroxytyrosol-rich extracts might be due to their abilities to lower serum TC, TG and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.     

实验性高脂血症恒河猴模型的初步建立及分析

目的建立实验性高脂血症恒河猴模型,为人类高脂血症研究提供理想动物模型。方法设计高脂实验饲料配方并检测常规营养成分,用高脂饲料诱导实验性高脂血症恒河猴模型,分别在2个月、4个月、6个月后监测体重、血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）等指标,对其血脂指标的变化趋势进行分析。结果模型组在实验2个月、4个月时的日采食量和摄入能量均低于对照组（P（0．05）,但体重则无明显变化（P〉0．05）;而在实验6个月时日采食量和摄入能量与对照组无显著性差异（P〉0．05）,体重有显著性差异（P〈0．05）;模型组与对照组的TC、TG、HDL—C、LDL—C在实验前和2个月比较无显著性差异（P〉0．05）;在4个月比较时TC、TG、LDL—C有显著性差异（P〈0．05）,而HDL无显著性差异（P〉0．05）;在6个月比较时TC、LDL—C有显著性差异（P〈0．05）,并且TC、LDL—C远远高于恒河猴血脂的正常参考值水平,而TG、HDL—C则无显著性差异（P〉0．05）;变化趋势分析结果为,模型组TC和LDL-C水平有递增趋势、TG水平则出现了先递减后逐渐恢复的趋势、HDL—C水平未出现明显变化趋势。结论模型组恒河猴具有高胆固醇血症和高低密度脂蛋白血症的特征,已经初步建立了实验性恒河猴高脂血症动物模型。     

Insights into Monascus biology at the genetic level

The genus of Monascus was nominated by van Tieghem in 1884, but its fermented product—red mold rice (RMR), namely red yeast rice, has been used as folk medicines, food colorants, and fermentation starters for more than thousands of years in oriental countries. Nowadays, RMR is widely developed as food supplements around the world due to its functional compounds such as monacolin K (MK, also called lovastatin) and γ-aminobutyric acid. But the usage of RMR also incurs controversy resulting from contamination of citrinin (a kind of mycotoxin) produced by some Monascus strains. In the past decade, it has made great progress to Monascus spp. at the genetic level with the application of molecular biology techniques to restrain the citrinin production and increase the yields of MK and pigment in RMR, as well as aid Monascus classification and phylogenesis. Up to now, hundreds of papers about Monascus molecular biology (MMB) have been published in the international primary journals. However, to our knowledge, there is no MMB review issued until now. In this review, current understanding of Monascus spp. from the view of molecular biology will be covered and insights into research areas that need to be further investigated will also be discussed.     

肥胖合并高脂血症患者血清食欲素A、25-羟维生素D3、瘦素水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性分析

摘要 目的：探讨肥胖合并高脂血症患者血清食欲素A（orexin A）、25-羟维生素D3[25-(OH)D3]、瘦素（Leptin）水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性。方法：选择2019年2月至2021年12月中国医科大学附属第四医院收治的105例肥胖合并高脂血症患者为研究组,另取同期在中国医科大学附属第四医院健康体检的73例志愿者为对照组。检测并对比两组血清orexin A、25-(OH)D3、Leptin、胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标水平的差异。采用Pearson相关性分析血清orexin A、25-(OH)D3、Leptin水平与胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标的相关性。结果：研究组血清orexin A、25-(OH)D3水平低于对照组,而Leptin水平高于对照组（P＜0.05）。研究组空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）水平均高于对照组（P＜0.05）。研究组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平高于对照组,而高密度脂蛋白胆固醇（HDL-C）水平低于对照组（P＜0.05）。研究组体质量指数（BMI）、腰臀比、腰高比均高于对照组（P＜0.05）。肥胖合并高脂血症患者的血清orexin A、25-(OH)D3水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈负相关,与HDL-C水平呈正相关（P＜0.05）;Leptin水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈正相关,与HDL-C水平呈负相关（P＜0.05）。结论：肥胖合并高脂血症患者血清orexin A、25-(OH)D3水平降低,Leptin水平升高,且与胰岛素抵抗、脂代谢紊乱及肥胖指标升高有关。     

瑞舒伐他汀与阿托伐他汀对冠心病高脂血症患者血脂及血浆ADMA水平的影响

目的:探讨瑞舒伐他汀与阿托伐他汀对冠心病高脂血症患者血脂及血浆不对称二甲基精氨酸(ADMA)水平的影响。方法:选取2016年3月-2017年12月四川大学华西医院收治的冠心病高脂血症患者210例为研究对象,随机分为研究组与对照组,每组各105例,研究组患者给予瑞舒伐他汀治疗,对照组给予阿托伐他汀治疗,均连续治疗8周。比较两组患者治疗前及治疗8周后血脂水平、ADMA水平及血清炎症因子水平、血管内皮功能指标水平,记录两组患者的不良反应发生情况。结果:两组患者治疗前及治疗8周后甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平比较无统计学差异(P0.05),两组患者治疗8周后TG、TC、LDL-C水平均较治疗前降低(P0.05),而HDL-C水平与治疗前相比无统计学差异(P0.05)。两组患者治疗8周后ADMA、超敏C反应蛋白(hs-CRP)、白介素-6(IL-6)水平均较治疗前降低,且研究组低于对照组(P0.05)。治疗8周后两组患者内皮素-1(ET-1)水平较治疗前降低,一氧化氮(NO)水平较治疗前升高(P0.05),且研究组患者ET-1水平低于对照组,NO水平高于对照组(P0.05)。研究组与对照组患者在治疗期间均未发生难以耐受的不良反应。结论:与阿托伐他汀相比,应用瑞舒伐他汀治疗冠心病高脂血症患者可改善血管内皮功能和TG、TC、LDL-C水平,减轻炎症反应,降低ADMA水平,无严重不良反应发生,值得临床推广。     

一株高产洛伐他汀红曲霉的筛选与液态发酵条件优化

【背景】洛伐他汀(lovastatin)是红曲霉的次生代谢产物,是重要的临床用降血脂药物。在液态发酵条件下,红曲霉的洛伐他汀产量较低,难以满足工业化生产的要求。【目的】筛选获得一株高产洛伐他汀的红曲霉株,并通过优化液态发酵条件提高洛伐他汀的产量。【方法】从红曲米中筛选获得一株高产洛伐他汀的红曲霉株,依据形态学特征、生理生化特性及18S rRNA基因序列分析对分离菌株进行鉴定;通过响应面法对其产洛伐他汀的液态发酵条件进行优化。【结果】获得一株产洛伐他汀的紫红曲霉(Monascus purpureus M4),该菌在甘油57.80g/L、酵母浸粉5.52 g/L、接种量为6.90%条件下,洛伐他汀产量(173.60 mg/L)较优化前提高了4.8倍。【结论】菌株M4产洛伐他汀最优液态发酵条件的建立,为洛伐他汀的大规模生产及该菌株的工业化应用提供了技术支撑。