Correlation between serum HbA 1c, γ-GT, ICAM-1 levels and cognitive impairment in elderly patients with hyperlipidemia complicated with cardiovascular diseases / 中华健康管理学杂志

Objective:To analyze the correlation between serum glycated hemoglobin (HbA 1c), γ-glutamyltranspeptidase(γ-GT) and intercellular adhesion factor-1 (ICAM-1) levels and cognitive impairment in elderly patients with hyperlipidemia complicated with cardiovascular disease. Methods:In this retrospective cohort study, 158 elderly patients who underwent examination and were diagnosed with hyperlipidemia complicated with cardiovascular disease at Beijing Anzhen Hospital Affiliated with Capital Medical University from January to December 2022 were selected as study subjects. The simple mental state scale (MMSE) was assessed in the subjects in combination with the subject′s level of education. Illiteracy≤17 points, primary school≤20 points, middle school and above≤24 points were classified as cognitive impairment group (67 cases), the rest were were classified into the non-cognitive impairment group (91 cases); and another 50 healthy elderly people who received physical examination in the same period were selected as the control group. The blood samples in the three groups were extracted to measure serum HbA 1c, γ-GT and ICAM-1. The correlation between HbA 1c, γ-GT and ICAM-1 levels with cognitive impairment were analyzed. Results:The serum levels of HbA 1c, γ-GT and ICAM-1 in the cognitive impairment group were all significantly higher than those in the non-cognitive impairment group and the control group [5.41%±1.04% vs 4.82%±0.95%, 4.39%±0.86%; (52.01±10.96) vs (41.28±9.23), (25.03±7.17) U/L; (336.61±85.36) vs (286.93±72.53), (143.52±64.20) g/ml], and the MMSE score was significantly lower [(20.19±2.85) vs (25.30±1.24), (27.14±1.56) points] (all P<0.05). Serum levels of HbA 1c, γ-GT and ICAM-1 were all significantly negatively correlated with MMSE score ( r=-0.512, -0.498, -0.563) (all P<0.05). The areas under the receiver operating characteristic curves (AUCs) for serum HbA 1c, γ-GT, and ICAM-1 levels in the assessment of cognitive dysfunction were 0.657, 0.816, and 0.691, respectively (all P<0.05). The optimal cut-off values were 5.115%, 47.65 U/L, and 304.58 g/ml, respectively. Conclusion:Serum HbA 1c, γ-GT and ICAM-1 levels in elderly patients with hyperlipidemia complicated with cardiovascular disease are negatively correlated with cognitive impairment, and have certain value for the evaluation and early diagnosis of cognitive impairment.

Different clinical effect between xiaozhi decoction in the treatment of hyperlipidemia in different classification of physical constitution in TCM / 中国现代医生

Objective To analyze the effect of Xiaozhi Decoction in the treatment of hyperlipidemiain different classification of physical constitution in TCM.Methods We screened 206 patients with Hyperlipidemia in our hospital and had been treated with drugs during May 2020 to March 2023.Totally 103 patients in the TCM group were treated with Xiaozhi Decoction,103 patients in the western medicine group were treated with atorvastatin.Selected total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and liver transaminase before and after a period of treatment.The non-high-density lipoprotein cholesterol(non-HDL-C)will be calculated,too.Results In the Phlegm-Dampness constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,TG and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in TC,LDL-C,non-HDL-C(P<0.05).In the Qi-Deficiency constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in non-HDL-C(P<0.05).In the Blood-Stasis constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the western medicine group only(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).In the Yin-Yang Harmony constitution,TC and non-HDL-C decreased significantly both in the TCM group(P<0.05).TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).Conclusion Xiaozhi Decoction is superior to the the atorvastatin in the treatment of hyperlipidemia for the Phlegm-Dampness constitution and Qi-deficiency constitution groups.But it is not superior to the atorvastatin in the treatment of hyperlipidemia for the Blood-Stasis constitution and Yin-Yang Harmony constitution groups.

Correlation between metabolic markers and blood lipid levels in kidney transplant recipients / 器官移植

Objective To analyze the co-expressed genes in blood lipid metabolism, hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients. Methods Co-expressed genes were screened from Comparative Toxicogenomic Database (CTD). Baseline data of 25 kidney transplant recipients were collected. The expression levels of ATP binding cassette subfamily A member 1(ABCA1), peroxisome proliferator activated receptor γ (PPAR-γ) and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1) were measured. All recipients were followed up. The concentrations of fasting blood glucose, glycosylated hemoglobin, triglyceride, total protein, albumin, globulin, cholesterol, high-density lipoprotein, low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1, 3, 6 and 12 months, and the incidence of hyperlipidemia in the recipients was analyzed. The correlation between ABCA1, GPIHBP1, PPAR-γ and clinical indexes was assessed. The diagnostic efficiency of related indexes for hyperlipidemia after kidney transplantation was evaluated. Results Three co-expressed genes including ABCA1, PPAR-γ and GPIHBP1 were screened. ABCA1 was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months, whereas negatively correlated with fasting blood glucose level at postoperative 3 months (all P<0.05). GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels, whereas positively correlated with tacrolimus blood concentration at postoperative 3 months (all P<0.05). PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels (both P<0.05). ABCA1, GPIHBP1 and PPAR-γ combined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic efficiency for hypertriglyceridemia after kidney transplantation (AUC=0.900). ABCA1, GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic efficiency for hypercholesterolemia after kidney transplantation (AUC=0.931). Conclusions ABCA1, GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees. No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation. Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control.

Exploration of the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats based on proteomics / 中国药房

OBJECTIVE To explore the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats. METHODS The experimental rats were divided into blank group （n＝9， no modeling）， model group （n＝8， modeling）， and Danshen decoction group （n＝9， modeling）. Starting from the 9th week of feeding with the high-fat diet， rats in the Danshen decoction group were given the corresponding medication solution （3.6 g/kg） intragastrically， while blank group and model group were given equal volume of normal saline， once a day， for 4 consecutive weeks. After 4 weeks of administration， the plasma levels of triglycerides （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured in each group of rats； the pathological and morphological changes of liver tissue were observed； the differential proteins between samples were screened out by TMT quantitative proteomic analysis； the expression levels of the key differentially expressed proteins in the liver， including epoxide hydrolase 2 （EPHX2）， perilipin 2 （PLIN2）， peroxisome proliferator activated receptor γ （PPAR γ） and glycogen synthase kinase-3β （GSK-3β）were detected. RESULTS Compared with the model group， the plasma levels of TC， TG and LDL-C in the Danshen decoction group were significantly reduced （P＜0.05）， while the level of HDL-C was significantly increased （P＜0.05）. The liver tissue of rats inmodel group showed uneven staining， disordered arrangement of liver plates， disappearance of liver sinusoids， nuclearcondensation or disappearance of some cells， swelling and fusion of cytoplasm， proliferation of connective tissue， and diffuse vacuolar-like fat droplet changes. The liver tissue of Danshen decoction group showed varying degrees of improvement in the above pathological and morphological. The results of differential protein analysis showed that the total number of differential proteins was 298 between the model group and the blank group； the total number of differential proteins was 139 between the model group and Danshen decoction group. Compared with the model group， the expression levels of EPHX2 and PLIN2 proteins in the liver tissue of rats in the Danshen decoction group were significantly reduced （P＜0.01）， while the expression levels of GSK-3β and PPARγ were significantly increased （P＜0.01）. CONCLUSIONS Danshen decoction has a significant improvement effect on the plasma lipid levels and the pathological and morphological of the liver tissue in hyperlipidemia model rats. Its regulatory mechanism may be related to the up-regulation of PPARγ and GSK-3β expression and down-regulation of EPHX2 and PLIN2 expression， and the signaling pathways involved may include PPAR-γ signal pathway.

Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology / 基础医学与临床

Objective To screen the potential pharmacological targets of Ningzhi capsule,a lipid-lowering tradi-tional Chinese medicine,and explore its mechanism of effect.Methods The components and predicted targets of Ningzhi capsule′s constituent drugs were obtained from BATMAN-TCM database.Hyperlipidemia-related targets were obtained from DisGeNET and GeneCards databases.The Venny2.1.0 tool was used to map drug targets and disease targets to obtain common targets as potential pharmacological targets.Protein-protein interaction analysis(STRING),gene ontology and pathway enrichment analysis(DAVID)were performed for the common targets.Finally,Swiss dock was used for molecular docking verification.Results A total of 1 432 predicted targets of Ning-zhi capsule and 87 targets related to hyperlipidemia were found and 32 common targets were screened which covered 64 potential pharmacological ingredients of Ningzhi capsule.Potential pharmacological targets were most abundant for turmeric root-tuber,turmeric and cattail pollen,and potential pharmacological ingredients were most abundant for sickle senna seed,turmeric and turmeric root-tuber.Apolipoprotein E(APOE),nitric oxide synthase 3(NOS3)and peroxisome proliferator activated receptor alpha(PPARA)had the highest hyperlipidemia correlation scores and more protein interactions,which were potential core targets.The biological processes related to DNA transcription were significantly enriched.Cholesterol metabolism,cGMP-PKG and PPAR signaling pathways were involved with APOE,NOS3 and PPARA,respectively.Molecular docking showed good binding activity.Conclusions There are many potential pharmacological ingredients of Ningzhi capsule and the key components for lowering lipids include turmeric root-tuber,turmeric,cattail pollen and sickle senna seed.APOE,NOS3 and PPARA are believed to be the key targets for lowering lipids with potential mechanism related to cholesterol metabo-lism,cGMP-PKG and PPAR signaling pathways.

Mechanism Study of"Atractylodes Macrocephala Koidz-Atractylodes Rhizoma"Drug Pair on the Prevention and Treatment of Hyperlipidemia Based on Network Pharmacology and Transcriptome Analysis / 浙江中医药大学学报

[Objective]To clarify the therapeutic effects of the"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair on hyperlipidemia(HLP)and to illuminate the primary mechanism via network pharmacology analysis.[Methods]HLP rat model was established by feeding rats with high-fat diet,and different doses of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair were administrated at the same time.At the end of the experiment,comparing the blood lipid levels of each group of rats and observing the lipid deposition in liver tissue.Using network pharmacology to predict the potential active ingredients and targets of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair for treating HLP,and further experimental verification.[Results]The drug pair of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"had a good effect on anti HLP induced by high-fat diet.Network pharmacology analysis showed that 3[3-acetoatractylodes atractylodes,wogonin,and 3 β-acetoxyatractylodes atractylodes were the potential active ingredients of the drugs in the treatment of HLP,and peroxisome proliferators-activated receptors(PPAR)signaling pathway-related PPARγ and fatty acid binding protein 4(FABP4)were the potential regulatory pathways and targets.The results of the validation experiment further confirmed that the drug pair could significantly up-regulate the expression of PPARy in liver tissue of rats with HLP.[Conclusion]The effect of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair on high-fat diet-induced HLP is related to the activation of PPARγ signaling pathway.

Mechanism of Total Saponin of Astragali Radix and Total Alkaloids of Nelumbinis Folium Against Hyperlipidemia Based on PPARγ/LXRα/ABCG1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport （RCT） in hyperlipidemia rats， and to discuss its mechanism. MethodSixty SD rats were randomly divided into control group， high-fat diet group， total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low （17 mg·kg-1+40 mg·kg-1）， middle （34 mg·kg-1+80 mg·kg-1）， high dose （68 mg·kg-1+160 mg·kg-1） groups and simvastatin （2.1 mg·kg-1） group， with 10 mice in each group. The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks. From the 3rd week， except for the control group and the high-fat diet group given distilled water， other groups were given corresponding drugs intragastric treatment for 4 weeks. The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue. The contents of total cholesterol （TC） and total bile acid （TBA） in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer. The mRNA and protein expression levels of peroxisome proliferators-activated receptors γ （PPARγ）， liver X receptors α （LXRα）， ATP-binding cassette transporter G1 （ABCG1） and cholesterol 7α-hydroxylase （CYP7A1） in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the contents or activities of TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， TBA， aspartate aminotransferase （AST）， alanine aminotransferase （ALT） in serum were significantly increased （P<0.01）， and the contents of high-density lipoprotein cholesterol （HDL-C） in the high-fat diet group were significantly decreased （P<0.01）. The hepatocyte was clearly swollen like ballooning degeneration， with a lot of fat vacuoles and red fat droplets. The contents of TC and TBA in liver tissue and feces were significantly increased （P<0.01）， and the mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly decreased （P<0.01）. Compared with the high-fat diet group， the contents or activities of TC， TG， LDL-C， TBA， AST， and ALT in the serum of rats in administered groups were significantly decreased （P<0.01）， while the content of HDL-C was significantly increased （P<0.01）. Hepatocyte swelling was significantly reduced， and the ballooning degeneration， fat vacuoles， and red lipid droplets in liver tissue were significantly decreased. The contents of TC and TBA in liver tissue were significantly decreased （P<0.05， P<0.01）， and the contents of TC and TBA in feces were significantly increased （P<0.05， P<0.01）. The mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly increased （P<0.05， P<0.01）. ConclusionTotal saponin of Astragali Radix-total alkaloids of Nelumbinis Folium has a positive effect on the prevention and treatment of hyperlipidemia rats， and its mechanism may be related to the activation of PPARγ/LXRα/ABCG1 signaling pathway and regulation of RCT.

Danlou tablet alleviates retinal ischemia-reperfusion injury through Keap1-Nrf2/HO-1 pathway / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the protective effect and mechanism of Danlou tablet on retinal ischemia-reperfusion injury(RIRI)in mice.METHODS: A total of 40 ApoE-/- mice were fed with high fat diet for 6 wk, and the RIRI model was established by anterior chamber infusion of pressurized saline. The mice were divided into control group(normal saline for 8 wk), RIRI model group(normal saline for 8 wk), and low-, medium-, and high-dose Danlou tablets groups [1, 2, and 4 g/(kg·d), respectively, for 8 wk]. The morphological changes of retina were observed by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated Nick-End Labeling(TUNEL)staining. The Western-blot assay was used to detect the expression of retinal tissue sample Kelch-like ech-associated protein 1(Keap1), nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), and superoxide dismutase(Sod2)proteins.RESULTS: Compared with the control group, the mouse retina was atrophic with thinning thickness and increasing cell apoptosis, down-regulation of Sod2 protein expression, and up-regulation of Keap1 protein expression in the RIRI model group(all P&#x003C;0.01). Compared with the RIRI model group, the retinal thickness increased in the medium- and high-dose of Danlou tablets groups(all P&#x003C;0.01), and the cell apoptosis of retina decreased in the low-, medium- and high-dose of Danlou tablets groups(all P&#x003C;0.05). There were no significant differences in the expression of Keap1 and HO-1 proteins of mouse retina tissue in the low-dose of Danlou tablets group(P&#x003E;0.05). The expression of Sod2, Nrf2 and HO-1 proteins up regulated, and the expression of Keap1 protein down regulated in the medium- and high-dose of Danlou tablets groups(all P&#x003C;0.05).CONCLUSION: Danlou tablet can alleviate RIRI-induced atrophy and thinning of retina and retinal cell apoptosis by regulating Keap1-Nrf2/HO-1 signal pathway and reducing oxidative stress.

Independent predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B

SUMMARY OBJECTIVE: There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection. METHODS: All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records. RESULTS: A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors. CONCLUSION: Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.

Evaluation of the therapeutic benefits of single daily dose versus alternate day dose of rosuvastatin in hyperlipidemia patients

Background: The common cause of mortality in India is related to complications of cardiovascular disease which has direct relation with the hyperlipidemia, diabetes mellitus, and hypertension. Rosuvastatin more efficacious than other statins in lesser dosage and having good safety profile. Aim and Objective: The present study was undertaken to evaluate the safety, efficacy of rosuvastatin 10 mg daily dose versus alternate day dose in hyperlipidemia patients. Materials and Methods: A total of 50 individuals with hyperlipidemia were selected in this prospective open label research. Patients were grouped as Group D with rosuvastatin daily dose and Group A with alternate day dose. Fasting plasma lipid profile was assessed in both groups on the 1st, 4th, and 6th weeks. Results: There is significant reduction in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and elevation of high-density lipoprotein (HDL) after 4 weeks and 6 weeks of the treatment in both the groups compared to baseline. The mean percentage reduction of total cholesterol was by 24% and 21.60% (P < 0.05) in Group D and Group A, respectively. The mean percentage reduction of LDL-C was by 33.50% and 31% (P < 0.05) Group D and Group A, respectively. The mean percentage improvement of HDL-cholesterol was by 19.89% and 17.09% (P < 0.05) in Group D and Group A, respectively. The mean percentage of reduction of TG was by 36.70% and 41.33% (P < 0.05) Group D and Group A. Conclusion: Rosuvastatin 10 mg on alternate days had the same efficacy in lowering cholesterol levels as taking it every day, also it may be a cost-effective alternative without sacrificing therapeutic benefits or side effects.

Effects of cleavage factor Im25 downregulation in vascular smooth muscle cells on hyperlipidemia in mice / 中华老年医学杂志

Objective:To investigate the impact of cleavage factor Im25(CFIm25)on VSMCs-specific knockdown in the context of hyperlipidemia.Methods:Mice models were constructed with specific knockout of CFIm25 in VSMCs(CFIm25f/+ TaglnCre)and control mice(TaglnCre).The mice were fed a normal diet or high-fat diet(HFD)for 18 weeks and their body weight changes were monitored.ELISA was used to measure serum total cholesterol(TC), triacylglycerol(TG), high-density lipoprotein(HDL-C)and low-density lipoprotein(LDL-C)levels.The extent of aortic lipid deposition in mice was assessed by oil red O staining.Results:During the feeding of a high-fat diet, CFIm25f/+ TaglnCre mice showed a significant increase in body weight compared to the control group[Male(1.01±0.06)g and(0.87±0.31)g, t=7.53, P<0.05; Female: (0.64±0.02)g and(0.35±0.04)g, t=9.68, P<0.05].After 18 weeks of high-fat diet feeding, CFIm25f/+ TaglnCre mice had significantly higher levels of TC[(6.80±0.35)mmol/L and(3.76±0.87)mmol/L, t=5.63, P=0.004], TG[(0.97±0.21)mmol/L and(0.42±0.10)mmol/L, t=4.08, P=0.015], and LDL-C[(5.20±0.30)mmol/L and(2.00±0.98)mmol/L, t=5.40, P=0.006]compared to the TaglnCre group.Specifically, TC levels increased by 80.72%, TG increased by 132.79%, and LDL-C increased by 160.32%.There was a significant increase in aorta lipid deposition and atherosclerotic plaque area in CFIm25f/+ TaglnCre mice( P<0.05). Conclusions:The research indicated that VSMCs-specific CFIm25 knockdown in mice further worsened hyperlipidemia and atherosclerotic lesions.

Lipid-lowering Activity of Quansanqi Tablets / 中国实验方剂学杂志

ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg-1 for mice， and 0.16， 0.32， 0.64 g·kg-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.

The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

Research Progress of Active Components of Traditional Chinese Medicine in Treatment of Hyperlipidemia by Activating PPARα Pathway / 中国实验方剂学杂志

Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism， which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels， which are the inducers of high-risk cardiovascular diseases such as atherosclerosis， pancreatitis and coronary heart disease. As a key target in lipid metabolism， peroxisome proliferator-activated receptor α （PPARα） is involved in a variety of metabolic activities， including fatty acid degradation， synthesis， transport， storage， lipoprotein metabolism， etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways， which is an important way to treat hyperlipidemia. At present， chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent， there are many adverse reactions and drug resistance. By reviewing the literature in recent years， the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids， alkaloids， phenols， terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway， thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation， and play a role in the treatment of hyperlipidemia. In this paper， we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway， so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.

Effects of plateau hypoxia on the pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemic rats / 中国药理学通报

Objective To study the effect of simulated high altitude hypoxia on the pharmacokinetics and pharmacodynamics of atorvastatin calcium in hyperlipidemia rats. Methods The wistar rats with hyperlipidemia induced by high-fat diet were divided into normoxia group and hypoxia group. Rats in the hypoxia group received a 14-day chronic hypoxia exposure at simulated an altitude of 5, 500 m. The two groups were given atorvastatin calcium(20 mg•kg

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect / 解剖学报

Objective To observe the effect of polyinosinic-polycytidylic acid ( Poly-IC ) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion ( I / R ) injury in fryperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I /R injury in fryperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I /R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly (P<0. 05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group (P<0. 05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0. 05) , and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability ( P < 0. 05 ) . No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0. 05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group ( P < 0 .05 ) , while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0. 05 ) . The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0. 05) , the expression of Bcl-2 was significantly decreased(P<0. 05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly ( P < 0. 05 ) , the expression of Bcl-2 increased significantly(P<0. 05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.

Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats / 解剖学报

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

Mechanism of Didang Decoction in prevention of anti-atherosclerosis and hyperlipidemia by HPLC-Q-TOF-MS/MS and network pharmacology based on theory of "nutrients return to heart and fat accumulates in channels" / 中国中药杂志

Atherosclerosis(AS) is caused by impaired lipid metabolism, which deposits lipids in the intima, causes vascular fibrosis and calcification, and then leads to stiffening of the vascular wall. Hyperlipidemia(HLP) is one of the key risk factors for AS. Based on the theory of "nutrients return to the heart and fat accumulates in the channels", it is believed that the excess fat returning to the heart in the vessels is the key pathogenic factor of AS. The accumulation of fat in the vessels over time and the blood stasis are the pathological mechanisms leading to the development of HLP and AS, and "turbid phlegm and fat" and "blood stasis" are the pathological products of the progression of HLP into AS. Didang Decoction(DDD) is a potent prescription effective in activating blood circulation, removing blood stasis, resolving turbidity, lowering lipids, and dredging blood vessels, with the functions of dispelling stasis to promote regeneration, which has certain effects in the treatment of atherosclerotic diseases. This study employed high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) to screen the main blood components of DDD, explored the targets and mechanisms of DDD against AS and HLP with network pharmacology, and verified the network pharmacological results by in vitro experiments. A total of 231 blood components of DDD were obtained, including 157 compounds with a composite score >60. There were 903 predicted targets obtained from SwissTargetPrediction and 279 disease targets from GeneCards, OMIM, and DisGeNET, and 79 potential target genes of DDD against AS and HLP were obtained by intersection. Gene Ontology(GO) analysis suggested that DDD presumably exerted regulation through biological processes such as cholesterol metabolism and inflammatory response, and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis suggested that signaling pathways included lipid and atherosclerosis, insulin resistance, chemo-carcinogenesis-receptor activation, and AGE-RAGE signaling pathways in diabetic complications. In vitro experiments showed that DDD could reduce free fatty acid-induced lipid accumulation and cholesterol ester content in L02 cells and improve cellular activity, which might be related to the up-regulation of the expression of PPARα, LPL, PPARG, VEGFA, CETP, CYP1A1, and CYP3A4, and the down-regulation of the expression of TNF-α and IL-6. DDD may play a role in preventing and treating AS and HLP by improving lipid metabolism and inflammatory response, and inhibiting apoptosis with multi-component, multi-target, and multi-pathway characteristics.

Preparation, pharmacokinetics and pharmacodynamics of curcumin nano emulsion / 药学实践与服务

Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. Cmax of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.

Comparative analysis of metabolic indicators in patients with persistent and non-persistent psoriasis / 中华皮肤科杂志

Objective:To identify factors influencing the recurrence of psoriasis, and to explore the association between the recurrence of psoriasis and metabolism-related markers.Methods:A retrospective investigation was conducted on the recurrence status of patients with psoriasis vulgaris, who visited the Department of Dermatology, Peking University Third Hospital from January 2016 to April 2023. Patients with recurrence intervals > 3 months were included in the non-rapid recurrence group (non-persistent psoriasis group), while patients with recurrence intervals ≤ 3 months were included in the rapid recurrence group (persistent psoriasis group). General conditions and relapse triggers were analyzed between the two groups. Metabolism-related laboratory data, as well as detection results of serum fatty acid-binding protein 4 (FABP4) and FABP5 in some patients, were collected, and relationships between these indicators and psoriasis recurrence were analyzed. Comparisons between groups were performed using t test, non-parametric test or chi-square test; linear regression analysis was performed to identify possible factors influencing the FABP levels, and multivariate logistic regression analysis to identify relapse triggers. Results:A total of 255 patients were collected, including 194 with non-persistent psoriasis and 61 with persistent psoriasis. There were no significant differences in gender, age (stratified every 30 years), course of psoriasis (stratified every 10 years), family history of psoriasis, and main therapies between the two groups (all P > 0.05). The patients in the non-persistent psoriasis group were more prone to recurrence due to seasonal effects ( χ2 = 18.98, P < 0.001). The proportion of patients with dyslipidemia was significantly higher in the persistent psoriasis group than in the non-persistent psoriasis group ( χ2 = 54.44, P < 0.001). Compared with the non-persistent psoriasis group, the persistent psoriasis group showed significantly increased body mass index and levels of triglycerides, uric acid, and C-reactive protein (all P < 0.05), but significantly decreased high-density lipoprotein cholesterol levels ( U = 3 348.00, P < 0.001). The levels of FABP4 and FABP5 were significantly higher in the persistent psoriasis group than in the non-persistent psoriasis group (both P < 0.05). In the linear regression model adjusted for body mass index and dyslipidemia, FABP4 levels were associated with recurrence status of psoriasis ( P < 0.001). Multivariate logistic regression analysis revealed a significant correlation between dyslipidemia and persistent psoriasis ( P < 0.001) . Conclusion:The psoriasis patients with recurrence intervals ≤ 3 months may be more prone to develop metabolic diseases such as dyslipidemia, and dyslipidemia and elevated FABP4 levels may be associated with the recurrence of psoriasis.