Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.

The Distribution Pattern of Traditional Chinese Medicine Syndromes in Patients with Hyperlipidemia

Objective: Hyperlipidemia is a representative nutritional metabolic disease in clinic, which is easy to induce atherosclerotic cardiovascular and cerebrovascular diseases, with complex classification. Traditional Chinese Medicine (TCM) syndrome aims to reflect the characteristics of diseases and is the basic principle of TCM treatment of diseases. This study aimed to summarize the distribution pattern of TCM syndromes in patients with hyperlipidemia. Methods: The frequency, characteristics and distribution of all TCM syndromes of 1012 patients with hyperlipidemia were analyzed. Results: The main disease types determined by frequency of 1012 patients included hypertriglyceridemia combined with hypo high-density lipoprotein cholesterolemia (19.76%), hypo high-density lipoprotein cholesterolemia (18.58%), hypercholesterolemia (16.50%), mixed hyperlipidemia (16.40%), and hypertriglyceridemia (15.12%). The distribution of TCM syndromes, in order of frequency, was as follows: Qi-deficiency and blood stasis syndrome (23.52%), liver depression and spleen deficiency (9.88%), syndrome of qi stagnation and blood stasis (9.29%), phlegm stasis syndrome (7.41%), and syndrome of yang deficiency of spleen and kidney (6.92%). Conclusion: Qi-deficiency and blood stasis syndrome and liver depression and spleen deficiency are the most common TCM syndromes in patients with hyperlipidemia.

Etitiological Relationship between Hyperlipidemia and Acute Pancreatitis

Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointestinal diseases in developed countries worldwide. Although many studies have been conducted, the pathogenesis still cannot be defined. Many studies have shown that this may be related to the triglyceride decomposition products free fatty acids are the main toxic substances, which can directly damage pancreatic acinar cells and vascular endothelial cells, causing tissue ischemia and acidic environment. Therefore, this paper focuses on the correlation of triglycerides and their decomposition products in plasma and provides evidence on the pathogenesis of AP and the disease progression of AP. Finally, the future potential to prevent and treat acute pancreatitis by some new drugs to reduce plasma triglycerides is summarized.

Mechanism of Rosae Rugosae Flos flavonoids in the treatment of hyperlipidemia and optimization of extraction process based on network pharmacology

This study aims to identify a natural plant chemical with hypolipidemic effects that can be used to treat high cholesterol without adverse reactions.Through network pharmacology screening,it was found that Rosae Rugosae Flos(RF)flavonoids had potential therapeutic effects on hyperlipidemia and its mechanism of action was discussed.TCMSP and GeneCards databases were used to obtain active ingredients and disease targets.Venn diagrams were drawn to illustrate the findings.The interaction network diagram was created using Cytoscape 3.8.0 software.The PPI protein network was constructed using String.GO and KEGG enrichment analysis was performed using Metascape.The results revealed 2 active flavonoid ingredients and 60 potential targets in RF.The key targets,including CCL2,PPARG,and PPARA,were found to play a role in multiple pathways such as the AGE-RAGE signaling pathway,lipid and atherosclerosis,and cancer pathway in diabetic complications.The solvent extraction method was optimized for efficient flavonoid extraction based on network pharmacology prediction results.This was achieved through a single factor and orthogonal test,resulting in an optimum process with a reflux time of 1.5 h,a solid-liquid ratio of 1:13 g/mL,and an ethanol concentration of 50%.

Optimization of extraction process for total flavonoids of Sophorae Flos for the treatment of hyperlipidemia based on network pharmacology and molecular docking

This study aimed to investigate the mechanism of action of Sophora Flos(SF)in the treatment of hyperlipidemia(HLP)using network pharmacology and molecular docking methods,and to optimize the extraction process of the predicted active components.The STRING database was used for protein interaction analysis and PPI network construction via Cytoscape 3.9.1.Pymol was employed for docking and visualization.An extensive review of SF identifi ed 6 active ingredients,297 related objectives,84 disease objectives,and 57 total objectives.After protein interaction and topology analysis,18 core targets were identified.These included 146 gene function entries(P<0.05).Active compounds,mainly flavonoids,can modulate the expression of various proteins such as TNF,IL-6,IL-1β,PPARG,and TGFB1 to achieve therapeutic effects on HLP.The network pharmacology and molecular docking results suggested that the active fl avonoids component in SF may be related to the treatment of hyperlipidemia.Therefore,the orthogonal experiment method was used to optimize the extraction process of total fl avonoid from SF using ethanol refl ux extraction,based on a single factor experiment.The effects of refl ux time,solid-liquid ratio,ethanol concentration,and other factors on the extraction of total fl avonoid from SF were investigated.The optimum process conditions were refl ux time of 1.25 h,solid-liquid ratio of 1:15 g/mL and ethanol concentration of 60%.Using these conditions,the purity of total fl avonoid extracted from SF was 70.33±0.22%.

Germinated brown rice relieves hyperlipidemia by alleviating gut microbiota dysbiosis

Hyperlipidemia is a frequent metabolic disorder that is closely associated with diet. It is believed that brown rice, containing the outer bran layer and germ, is beneficial for the remission of hyperlipidemia. This study established a rat model of hyperlipidemia by feeding a high-fat diet. The hypolipidemic potential of germinated brown rice(Gbrown) and germinated black rice(a germinated black-pigmented brown rice, Gblack) were explored in the model rats, mainly in the aspects of blood lipids, lipases, apolipoproteins, and inflammation. The gut microbiota in hyperlipidemic rats receiving diverse dietary interventions was determined by 16S rDNA sequencing. The results showed that the intervention of Gbrown/Gblack alleviated the hyperlipidemia in rats, evidenced by decreased TC, TG, LDL-C, and apolipoprotein B, and increased HDL-C, HL, LPL, LCAT, and apolipoprotein A1. Gbrown/Gblack also weakened the inflammation in hyperlipidemia rats, evidenced by decreased TNF-α, IL-6, and ET-1. In addition, 16S rDNA sequencing revealed that the diet of Gbrown/Gblack elevated the abundance and diversity of gut microbiota in hyperlipidemia rats. At the phylum level, Gbrown/Gblack decreased Firmicutes, increased Bacteroidetes, and decreased the F/B ratio in hyperlipidemia rats. At the genus level, Gbrown/Gblack decreased Streptococcus and increased Ruminococcus and Allobaculum in hyperlipidemia rats. Some differential microbial genera relating to lipid metabolism were also determined, such as the Lachnospira and Ruminococcus in the Gblack group, and the Phascolarctobacterium, Dorea, Turicibacter, and Escherichia-Shigella in the Gbrown group. Notably, the beneficial effect of Gblack was stronger than Gbrown. To sum up, the dietary interventions of Gbrown/Gblack contributed to the remission of hyperlipidemia by alleviating the dysbiosis of gut microbiota.

Biochanin-A attenuates high-fat diet and streptozotocin-induced hyperlipidemia and oxidative stress in rats by improving antioxidant status and lipid metabolic markers

Objective:To determine how biochanin-A(BCA)affects high-fat diet and streptozotocin-induced pathological changes in lipid metabolism and antioxidant status in diabetic rats.Methods:Diabetic rats were orally administered BCA(10 mg/kg body weight)for 30 days to investigate its effects on lipid profiles and oxidative stress markers in the liver and kidney.In addition,the mRNA expression of antioxidant and lipid metabolism enzymes in the liver was examined.Results:BCA attenuated hyperlipidemia by regulating mRNA expressions of HMG-CoA reductase,fatty acid synthase,carnitine palmitoyl transferase,and acetyl-CoA carboxylase.Additionally,BCA reduced high-fat diet and streptozotocin-induced oxidative stress by suppressing lipid peroxidation,improving superoxide dismutase,catalase,and glutathione peroxidase levels,and upregulating mRNA expressions of these enzymes.Conclusions:BCA may be a promising nutraceutical for the treatment of dyslipidemia and oxidative stress associated with diabetes.

Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites:A Randomized,Double-Blind,Placebo-Controlled Clinical Trial

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62)were randomly assigned to receive placebo(N=31)or B.longum CCFM1077(1×1010colony-forming units(CFUs)per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA)sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p<0.01)and LDL-C(p<0.01)in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine)and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms)were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.

Efficacy evaluation of Shenlan oral liquid in the treatment of experimental thrombosis and hyperlipidemia

Objective:To explore the therapeutic effect of Shenlan oral liquid on thrombosis rats and hyperlipidemia mice.Methods:Male Wistar rats were divided into four groups randomly:the control group,the Shenlan oral liquid groups(high dosage and low dosage),and the positive control group.Rats in the control group were treated with dd water intragastriclly;in the positive control group,rats were treated intragastric with aspirin.Rats were treated with different drugs intragastric for continuous 22 d.In the hyperlipidemia experiment,mice were fed with high-fat diet to induce hyperlipidemia model mice,then randomly divided into five groups;the control group,the model group,the atorvastatin calcium positive control group,and the Shenlan oral liquid groups(high dosage and low dosage).The serum lipid and body weight changes of mice were observed after 6 weeks.Animals in Shenlan oral liquid high and low dosage were treated intragastric with six times and double the clinical dose.Results:After treatment,the mix blocking rate and average blocking rate of the vascular after electrical stimulation were obviously reduced in aspirin group,and Shenlan oral liquid high and low dose groups(P<0.05 or P<0.01).The maximum aggregation rate was significantly lower than that of control group(P<0.05 or P<0.01),and the normal coagulation function was not affected.In the treatment of hyperlipidemia,the effects of Shenlan oral liquid were measured on the total cholesterol(TC),triacylglycerol(total triglyceride,TG),low density lipoprotein(LDL-C)and high-density lipoprotein(HDL-C)with the hyperlipidemia mice.After 2 weeks administration,the serum TG level of Shenlan oral liquid high-dose group decreased compared with the model group.The TG level of serum in Shenlan oral liquid high-dose group significantly decreased compared with the model group from the fourth week(P<0.05).After 6 weeks administration,Shenlan oral liquid high-dose and low-dose group and positive drugs reached to the same therapeutic effect.Compared with model group,serum TG level was significantly decreased(P<0.05 or P<0.01).Conclusion:Shenlan oral liquid can decrease the thrombosis formation in rats and inhibit the lipid level in blood in hyperlipidemia mice.

Mechanism of Wulan Shisanwei Decoction in Treating Hypertension Complicated with Hyperlipidemia Based on Network Pharmacology

[Objectives]To screen out the main effective components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia based on the method of network pharmacology,predict the target and explore the possible mechanism.[Methods]13 components of Wulan Shisanwei Decoction were searched on the TCMSP data platform,the corresponding active components were found and the corresponding targets were searched in Pubchem database.GeneCards database was used to screen the corresponding targets of hypertension and hyperlipidemia.The core target PPI network of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was constructed by processing in STRING database.The effective data were imported into Cytoscape 3.8.0 to analyze the network topology parameters,and they were screened according to the degree value greater than the average value.Finally,the relevant information about the core target of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia was obtained.GO enrichment analysis and KEGG pathway analysis were carried out for core targets in DAVID database.The visualization map of"drug-component-target-disease"was drawn by Cytoscape 3.8.0.[Results]A total of 85 active components were obtained from Wulan Shisanwei Decoction,and there were 1532 corresponding targets.A total of 303 key targets were obtained by intersecting corresponding drug targets with disease targets.3178 biological processes were obtained by GO analysis(P<0.05)and 192 signaling pathways were obtained by KEGG enrichment analysis(P<0.05).[Conclusions]It was predicted that the main active components of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia were stigmasterol,acacetin,pectolinarigenin,isorhamnetin,alizarin,quercetin,nordamnacanthal,kaempferol,luteolin,glyceollin,kushenol,t,3-methylkempferol,ellagic acid,etc.20 core targets were selected in the treatment of hypertension complicated with hyperlipidemia:SRC,STAT3,HSP90AA1,MAPK1,MAPK3,PIK3R1,HRAS,GRB2,PIK3CA,AKT1,PTPN11,ESR1,LCK,EGFR,FYN,EP300,RELA,JUN,LYN,RHOA.These targets were involved in PI3K-Akt signaling pathway,lipid and atherosclerosis,proteoglycan in cancer,Ras signaling pathway,etc.to exert a response to oxidative stress,cellular response to chemical stress,peptidyl-tyrosine phosphorylation and peptide tyrosine modification,and can intervene in the early stage of the disease.It may be the potential mechanism of Wulan Shisanwei Decoction in the treatment of hypertension complicated with hyperlipidemia.

Effects of moxibustion at 46°C on blood lipids and related indicators of thoracic aortic endothelium in a hyperlipidemia rat model

Objective:To observe the effects of moxibustion at different temperatures(38℃,46℃)on blood lipids,endothelial morphology of the thoracic aorta,serum endothelin-1(ET-1),calcitonin gene-related peptide(CGRP),nitric oxide(NO),and endothelial NO synthase(eNOS)in hyperlipidemic rats.Methods:Using the random number table method,60 Sprague Dawley rats were randomly and evenly divided into blank,model,38℃-moxibustion,and 46℃-moxibustion groups.Rats in the 3 experimental groups were fed a high-fat feed to model hyperlipidemia in rats.Rats in the 38℃-moxibustion and 46℃-moxibustion groups were moxibustion on the Shenque and bilateral Zusanli acupoints for 10 minutes each,once every other day for 4 weeks,at temperatures of 38±1℃ and 46±1℃.After that,rat blood samples were collected to detect blood lipids and ET-1,CGRP,eNOS and NO.Take the endotheal tissue of the thoracic aorta to do HE staining.Results:(1)The serum total cholesterol,triglycerides,and low-density lipoprotein cholesterol of rats in the 46℃-moxibustion group were significantly lower than those in the model and 38℃-moxibustion groups.(2)Revealed by hematoxylin and eosin staining,showed necrosis in the local vascular endothelial cells and mild inflammatory cell infiltration in the tunica adventitia of the hyperlipidemic rats.These endothelial morphologies did not improve significantly after moxibustion at 38℃ but did improve at 46℃.(3)Compared with the blank group,serum ET-1 was significantly higher and serum CGRP,NO,eNOS were significantly lower in the model group.Compared with the model and the 38℃-moxibustion groups,serum ET-1 was significantly lower and serum CGRP,NO,eNOS were significantly higher in 46℃-moxibustion groups.Conclusion:Moxibustion at 46℃ effectively regulated blood lipids,improved the morphology of the vascular endothelium,and protected vascular endothelial function.

不同年龄段早发冠心病患者临床特征及危险因素的分析

目的:探究不同年龄段早发冠心病患者的临床特征以及危险因素。方法:选择2021年6月至2022年8月,在北京安贞医院门诊诊断为早发冠心病的380例患者作为研究对象,40岁<患者年龄≤59岁为中青年组,中青年组150例,59岁<患者年龄≤65岁为老年组,老年组230例。对两组患者的临床资料、实验室检查指标、冠心病的影响因素、冠状动脉病变情况及介入治疗后安全性,进行单因素分析,对单因素分析差异有统计学意义的因素带入多元线性回归,分析相关影响因素。结果:两组患者一般资料对比,仅性别差异有统计学意义(P<0.05)。与中青年组相比,老年组患者的Cr、血浆凝血酶原时间(prothrombin time,PT)、FIB水平明显高,但老年组的谷氨酸转肽酶、TG、Hcy以及PLT都明显低于中青年组,差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,Hcy、FIB进入回归模型;老年组3支病变者发生率均比较高(P<0.05),冠状动脉造影术后总的不良事件发生率更多(P<0.05)。结论:不同年龄段早发冠心病患者在临床实验室指标及预后方面存在差异。

瑞舒伐他汀联合康复训练治疗冠状动脉粥样硬化性心脏病合并高脂血症临床观察

目的探讨瑞舒伐他汀联合康复训练治疗冠状动脉粥样硬化性心脏病(简称冠心病)合并高脂血症的临床疗效。方法选取医院2020年1月至2022年12月收治的冠心病合并高脂血症患者144例,按随机数字表法分为观察组和对照组,各72例。对照组患者予常规治疗和瑞舒伐他汀,观察组患者增加康复训练,两组均治疗12周。结果治疗后,两组患者的总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平均明显低于治疗前,高密度脂蛋白胆固醇水平明显高于治疗前(P<0.05),且观察组均明显优于对照组(P<0.05);两组患者的左室射血分数、每分输出量(CO)水平均明显高于治疗前,血清心肌肌钙蛋白I明显低于治疗前(P<0.05),且观察组均明显优于对照组(P<0.05);两组患者的健康调查简表(SF-36)生理功能、生理职能、活力、社会功能、总体健康评分均明显高于治疗前(P<0.05),且观察组明显高于对照组(P<0.05)。结论瑞舒伐他汀联合康复训练可有效改善冠心病合并高脂血症患者的心功能,调节血脂水平,提高生活质量。

犬脂血性葡萄膜炎的病例报告

葡萄膜炎是犬常见的复杂眼科疾病,潜在病因种类多,后遗症严重,若未能尽早做出明确诊断和积极治疗,该病可能导致动物长期疼痛和失明等并发症,甚至可能需要通过眼球摘除术来缓解动物的痛苦。因此,对于葡萄膜炎病例,需要尽快确定病因,有效开展对因和对症治疗。脂血性葡萄膜炎是一种特殊的葡萄膜炎。由于大量脂蛋白通过血-房水屏障进入前房,使前房表现出特征性的乳白色外观。该病与高脂血症密切相关,临床诊断相对简单。治疗原则包括针对高脂血症的控制和针对葡萄膜炎的对症治疗,预后通常较好。2021年6月,中国农业大学动物医院接诊1例犬脂血性葡萄膜炎的病例,治疗后患犬恢复良好。本文通过论述该病例的诊断和治疗过程,以期为临床上此类疾病的诊疗提供参考依据。

CDR132L改善高血压合并高脂血症小鼠血管重构和功能

[目的]观察CDR132L(miR-132反义核苷酸)对高血压合并高脂血症小鼠血管重构和功能的影响,并探究其可能的作用机制。[方法]随机选择30只8周龄雄性C57BL/6小鼠,分为三组:对照组、模型组和CDR132L组,每组10只。对照组接受标准饲料喂养,模型组和CDR132L组给予N-硝基-L-精氨酸甲酯(L-NAME)和高脂食物联合喂养来诱导高血压和高脂血症。CDR132L组给予20 mg/kg CDR132L腹腔注射,1次/周,连续6周,对照组和模型组腹腔注射相同剂量的生理盐水溶液。尾套法测量小鼠尾动脉收缩压和舒张压,血脂、血糖检测由全自动生化分析仪完成,HE染色观察胸主动脉结构,血管环试验观察小鼠胸主动脉内皮依赖性舒张反应,定量基因扩增检测胸主动脉miR-132表达水平,Western blot检测胸主动脉Gab1和内皮型一氧化氮合酶(eNOS)蛋白表达水平。[结果]与对照组相比,模型组小鼠收缩压、舒张压、血清甘油三酯、血清总胆固醇和体质量均明显升高(P<0.05),胸主动脉内膜凹凸不平,血管壁厚度不均,中膜平滑肌细胞的排列呈现不规则状态,血管壁上存在大量脂肪积聚,胸主动脉内皮依赖性舒张反应减低(P<0.05),胸主动脉miR-132表达水平明显增加(P<0.05),Gab1和eNOS蛋白表达水平明显降低(P<0.05)。与模型组相比,CDR132L组小鼠收缩压、舒张压、血清甘油三酯、血清总胆固醇和体质量均无统计学差异(P>0.05),胸主动脉管腔内膜较完整光滑,血管壁厚度较均一,中膜平滑肌细胞的排列较为有序,血管壁仅存在少量脂肪积聚,胸主动脉内皮依赖性舒张反应增强(P<0.05),胸主动脉miR-132表达水平明显降低(P<0.05),Gab1和eNOS蛋白表达水平明显增加(P<0.05)。[结论]CDR132L能改善高血压合并高脂血症小鼠血管重构及内皮依赖性舒张功能,这一作用可能与其降低胸主动脉miR-132表达水平,进而上调胸主动脉Gab1和eNOS蛋白表达水平有关。

都匀毛尖红茶水提物对高脂血症小鼠的脂质代谢研究

目的:通过观察都匀毛尖红茶水提物对高脂血症小鼠脂质代谢的影响,掌握其抗高脂血症的保健作用效果,为都匀毛尖红茶的推广提供理论支撑。方法:将成功建立高脂血症模型后的小鼠分成模型对照组(MC组)、阳性对照组(PC组)、都匀毛尖低剂量组(HL组)、中剂量组(HM组)、高剂量组(HH组),每组10只;另设空白对照组(NC组)10只。分组后,除NC组外,其它组继续给予高脂饮食。MC组不给予任何干预,PC组给予辛伐他汀分散片混悬液灌胃,都匀毛尖红茶组按照相应剂量灌胃(低、中、高剂量分别为50、100、200 mg/kg),1次/d,连续干预14 d。检测小鼠脏器指数、血清C、TG、LDL-C、HDL-C、ALT、AST、SOD、MDA等指标,镜下观察肝脏病理形态。结果:与NC组比较,各造模组小鼠肝脏质量明显增加及肝脏系数明显升高(P<0.05),血清TC、TG、LDL-C、ALT、AST、MDA明显升高,而血清HDL-C及SOD活力明显降低。同时,各造模组小鼠肝脏呈现不同程度的肝细胞脂肪变性表现。与MC组比较,PC组、HL组、HM组、HH组小鼠呈现不同程度体质量减轻及肝脏系数降低(P<0.05);血清TC、TG、LDL-C、ALT、AST、MDA不同程度降低,同时HDL-C及SOD活力不同程度升高;小鼠肝脏病理显示肝细胞脂肪变性均不同程度减轻。其中,以PC组、HM组、HH组效果较为明显。结论:用都匀毛尖红茶,可以有效调剂血清脂质代谢,减轻脂肪氧化作用,保护肝脏细胞,从而有效降低高脂血症对于人体危害,十分适合患有高脂血症状态人群的日常保健饮用。

综合医院血脂管理门诊模式建设探索与实践

背景目前我国城乡居民死亡原因排名第一位的疾病仍然是心血管疾病,其中最主要的是动脉粥样硬化性心血管疾病,而低密度脂蛋白胆固醇升高是其主要危险因素。目的通过建立新型血脂管理门诊模式,分析新模式建立前后患者血脂异常的知晓率、合理用药比例、患者依从性及用药达标率。方法2023-09-01—2024-02-28,南京医科大学附属苏州医院通过整合医学资源建立了基于科研项目为基础的综合医院血脂管理门诊模式。该模式以“血脂异常患者”门诊为载体,联动专科医生、全科医生对血脂异常患者开展规范化管理,优化就诊和随访流程,有效筛查血脂异常人群和诊断高脂血症患者并提供正确的治疗方法。结果纳入慢病管理的血脂异常患者人群由以往分散模式,转变为血脂管理门诊整体、规范、集中管理,且管理的患者人数较前显著增加。血脂管理门诊模式建立后,门诊初次就诊患者规范用药比例由25.3%(147/580)提升到30.3%(242/798),坚持用药比例由32.7%(190/580)提升到41.6%(332/798),用药达标率由15.8%(92/580)提升到22.5%(180/798)(P<0.05)。结论通过实施“全专结合”的血脂管理门诊模式,纳入慢病管理的血脂异常患者人数明显增加,患者规范用药比例、用药依从性和用药达标率有所提高。该模式既有利于科研项目实施,又能培养医学人才,有助于提高全科医生和研究生及规培生的科学研究能力和专业技术水平。

辛伐他汀预防小鼠高脂血症合并脑缺血损伤及其对时钟基因的调控

目的探讨辛伐他汀对小鼠高血脂合并脑缺血再灌注损伤(CIRI)的预防作用及机制。方法将60只C57BL/6J小鼠分为假手术组、CIRI组〔采用大脑中动脉阻塞再灌注法(MCAO/R)制备小鼠CIRI模型〕、高脂组(ip给予泊洛沙姆407)、高脂+CIRI组(ip给予泊洛沙姆407,24 h后MCAO/R造模)、高脂+CIRI+辛伐他汀5和10 mg·kg^(-1)组(先ig给予辛伐他汀连续7 d,后按照高脂+CIRI组处理)。再灌注24 h后,对各组小鼠进行神经功能缺损评分;转棒实验测定掉落潜伏期;自主活动测试小鼠活动次数;TTC染色测定脑梗死体积;激光散斑血流成像检测小鼠脑血流量;取全血分离血清,并测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)含量;实时荧光定量PCR和Westen印迹法检测小鼠右脑皮质时钟基因Rev-erbα和Bmal1 mRNA及蛋白表达水平。结果与假手术组相比,CIRI组小鼠神经功能缺损评分升高(P<0.01),掉落潜伏期缩短(P<0.01),活动次数减少(P<0.01)。与CIRI组相比,高脂+CIRI组小鼠神经功能损伤加重(P<0.01);脑梗死体积显著增加(P<0.01);脑血流量显著降低(P<0.01);血清中TC,TG,LDL-C及MDA含量显著升高(P<0.01),GSH-PX水平显著降低(P<0.01);脑皮质Rev-erbαmRNA和蛋白表达水平显著下调(P<0.01);Bmal1 mRNA和蛋白表达水平显著上调(P<0.01)。与高脂+CIRI组相比,高脂+CIRI+辛伐他汀5和10 mg·kg^(-1)组小鼠神经功能损伤减轻(P<0.01);脑梗死体积显著减小(P<0.01);脑血流量显著增加(P<0.01);血清中TC,TG,LDL-C及MDA含量显著降低(P<0.01),GSH-PX水平显著升高(P<0.01);脑皮质Rev-erbαmRNA和蛋白表达水平显著上调(P<0.01);Bmal1 mRNA和蛋白表达水平显著下调(P<0.01)。结论辛伐他汀预防性给药能有效减轻小鼠高脂血症合并CIRI,其机制与其降血脂及调节时钟基因表达有关。

基于细胞铜死亡分析香砂六君子汤减少脾虚高脂血症大鼠肝脏组织脂质沉积的作用机制

目的从细胞铜死亡的角度分析中药香砂六君子汤减少脾虚高脂血症大鼠肝脏组织脂质沉积的作用机制。方法将18只健康SD大鼠随机均分为正常组、脾虚高脂血症组、中药组。脾虚高脂血症组和中药组采用游泳力竭和高脂饲料喂养的复合方法造模,正常组仅给予普通饲料。造模12周后,中药组进行香砂六君子汤(11.34 g·kg-1)灌胃干预,正常组与脾虚高脂血症组给予同体积0.9%氯化钠溶液灌胃,灌胃干预4周后检测各组大鼠血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、肝脏脂积变化;PCR Array技术检测与铜死亡相关基因的表达。结果与正常组比较,脾虚高脂血症组血清中TC、TG、LDL-C水平显著升高(P<0.01),HDL-C水平显著降低(P<0.01);脾虚高脂血症组大鼠肝脏脂质沉积明显。与脾虚高脂血症组比较,中药组TC、TG、LDL-C水平显著降低(P<0.01),HDL-C水平显著升高(P<0.01);中药组大鼠肝脏脂质沉积明显减少。PCR Array共检测出11个铜死亡相关基因。与正常组比较,脾虚高脂血症组肝脏铜死亡差异表达基因7个;与脾虚高脂血症组比较,中药组肝脏铜死亡差异表达基因6个;脾虚高脂血症组与中药组铜死亡共同差异表达基因5个。脾虚高脂血症组与正常组、中药组与脾虚高脂血症组差异表达均发生上调≥1倍或下调≤1倍的基因3个,2种比较方法结果取交集,共同的差异表达基因为Dld和Gls,这2个基因均能够调控线粒体铜死亡水平。qPCR验证结果显示,Dld基因表达与PCR芯片结果一致。结论肝脏铜死亡相关基因(Dld、Gls)表达异常可能是血脂代谢异常的潜在机制,也可能是香砂六君子汤防治脾虚高脂血症的重要作用靶标。

隐丹参酮对STZ诱导的糖尿病肾病模型大鼠的肾脏保护作用及机制

目的探讨隐丹参酮对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病(diabetic nephropa-thy,DN)模型大鼠肾脏保护作用及可能作用机制.方法60只大鼠按随机数字表法分为对照组,DN模型组,隐丹参酮低、中、高剂量组(15、30、60 mg·kg^(-1)·d^(-1))和二甲双胍组(200 mg·kg^(-1)·d^(-1)),除对照组,其余均以STZ诱导制成DN大鼠模型.给药结束24 h后,检测大鼠的空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白中胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、24h尿蛋白定量、血尿素氮(BUN)、血清肌酐(Scr)、超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)指标;Western blot检测TGF-β1/Smad3信号通路相关蛋白表达水平.结果生化指标检测结果显示:经药物干预后,二甲双胍组和隐丹参酮中、高剂量组大鼠FPG、尿蛋白、BUN、Scr、MDA、ROS、TG、TC、LDL-C水平、全血高切黏度、全血中切黏度、全血低切黏度及血浆黏度水平均较DN模型组降低,而SOD、HDL-C水较DN模型组升高.Western blot结果显示:经药物干预后,二甲双胍组和隐丹参酮中、高剂量组大鼠TGF-β1蛋白表达水平、p-Smad3/Smad3比值较DN模型组降低,而p-Smad7/Smad7比值较DN模型组升高.结论隐丹参酮可改善STZ诱导的DN模型大鼠的糖脂代谢、氧化应激及血液流变学情况,提升大鼠的肾功能,其保护作用可能与激活TGF-β1/Smad3信号通路有关.