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Food Science and Human Wellness 2024年第1期13卷 472-481页

作者： Wenjun Xue Wenzhu Zhao Sijia Wu Zhipeng Yu School of Food Science and Engineering Hainan UniversityHaikou 570228China College of Food Science and Engineering Bohai UniversityJinzhou 121013China Lab of Nutrition and Functional Food Jilin UniversityChangchun 130062China

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully *** study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic *** peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

关键词： ACE inhibitory peptide Kidney Mechanism Metabolomics spontaneously hypertensive rats

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第7期13卷 287-295页

作者： Yucinda YY Khor Siew-Keah Lee Dharmani Devi M Wei Chih Ling Department of Pre-clinical Sciences M.Kandiah Faculty of Medicine and Health SciencesUniversiti Tunku Abdul RahmanSelangorMalaysia Department of Pharmacology Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 *** endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of *** vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also ***,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was ***:The systolic blood pressure was significantly decreased in SHR treated with *** impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR *** also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in ***:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)*** increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

关键词： Epigallocatechin-3-gallate Vascular protection Antihypertension Tetrahydrobiopterin Cyclic guanosine monophosphate Angiotensin typeⅠreceptor spontaneously hypertensive rats

Inflammatory reaction versus endogenous peroxisome proliferator- activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats

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Chinese Medical Journal 2008年第22期121卷 2305-2311页

作者： SUN Li KE Yan ZHU Chun-yun TANG Ning TIAN Deng-ke GAO Yue-hong ZHENG Jian-pu BIAN Ka Murad Research Institute for Modernized Chinese Medicine Shanghai University of Traditional Chinese Medicine Shanghai 201203 China Tianjin Medical University General Hospital Tianjin 300052 China Division of Nitric Oxide and Inflammatory Medicine E-Institute of Shanghai Universities Shanghai 201203 China Department of Integrative Biology and Pharmacology Institute of Molecular Medicine University of Texas Medical School 6431 Fannin Houston TX 77030 USA

Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods l]ssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbony

关键词： spontaneously hypertensive rats inflammation peroxisome proliferator-activated receptors

Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in spontaneously hypertensive rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第3期27卷 245-247页

作者：孙联平郑智 Department of Emergency Medicine Bejing Chuiyangliu Hospital Department of Emergency Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.

关键词： salvia miltiorrhiza Bge spontaneously hypertensive rats left ventricular hypertrophy tumor necrosis factor-α

Effect of Salvia Miltiorrhiza on Left Ventricular Hypertrophy and Cardiac Aldosterone in spontaneously hypertensive rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第4期22卷 302-304页

作者：韩少杰郑智任大宏 DepartmentofEmergencyMedicine DepartmentofPathology

Chronic treatment with Salvia Miltiorrhiza preventing left ventricular hypertrophy (L VH) and its possible mechanism- inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were *** Wistar- kyoto (WKY ) rats and SHRs were *** of SHRs was treated with Salvia Miltiorrhiza for 12 *** blood pres- sure (SBP) and left ventricular mass index were *** of heart tissue were stained with HE method and Van Gieson *** volume fraction was determined in the leftven- tricle by automatically quantitative m *** aldosterone concentration was measured by radioimm *** results indicated thatcom pared with WKY rats,SHRs exhibited high- er SBP,left ventricular collagen volume fraction,and aldosterone concentration (all P<0 .0 5 ) . After the treatm ent with Salvia Miltiorrhiza,SBP,left ventricular collagen volum e fraction,and aldosterone concentration in SHR were decreased as compared with control group (P<0 .0 5 ) ex- cept *** was concluded thatchronic treatment with Salvia Miltiorrhiza could preventleftven- tricular hypertrophy in SHR,significantly inhibit collagen compositions in left *** m echanism was probably related with the inhibition of the cardiac aldosterone action.

关键词： Salvia Miltiorrhiza spontaneously hypertensive rats leftventricular hypertrophy al- dosterone

Effects of Total Flavonoids ofHippophae *** Intracellular Free Calciumin Cultured Vascular Smooth Muscle Cells of spontaneously hypertensive rats and Wistar-Kyoto rats

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Chinese Journal of Integrative Medicine 2005年第4期11卷 287-292页

作者：朱福黄波胡春燕蒋庆渊卢振国陆铭王美华龚敏乔春萍陈维黄盼华 Cardiovascular Depart ment Nanhui District CentralHospital Shanghai 201300 Cardiovascular Depart-ment Shanghai Renhe Hospital Internal Medicine De-part ment Longhua Hospital Shanghai University of Tradi-tional Chinese Medicine

Objective: To explore the effects of total flavonoids of Hippophae rhamnoides L. (TFH), quercetin (Que) and isorhamnetin (Isor) on the intracellular free calcium (Ca~ 2+ _ i) in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY).Methods: Fluo 3-acetoxymethylester(Fluo-3/AM) was used to observe the effects of TFH (100mg/L) and its essential monomers, namely Que (10~ -4 mol/L) and Isor (10~ -4 mol/L) on changes of Ca~ 2+ _ i in cultured SHR and WKY VSMC (abbr. to Ca-SHR & Ca-WKY) following exposure to high K~+, norepinephrine (NE) and angiotensin Ⅱ(AngⅡ), and to compare with the effects of verapamil (Ver). Results: (1) TFH, Que and Isor had inhibitory effects on resting Ca-SHR (P0.05). (2) High K~+ could increase Ca-SHR more significantly than Ca-WKY (P<0.05); TFH, Que and Isor could inhibit the elevation of Ca~ 2+ _ i induced by high K~+-depolarization, with the effects similar to that of Ver, and the effect on Ca-SHR was more significant than that on Ca-WKY (P<0.05). (3) NE and AngⅡcould increase Ca-SHR more significantly than Ca-WKY (P<0.05), TFH, Que and Isor had remarkably inhibitory effect on the elevation of Ca-SHR and Ca-WKY induced by NE or AngⅡ. (4) In the absence of extracellular Ca~ 2+ , TFH, Que and Isor also had certain inhibitory effect on Ca-SHR and Ca-WKY induced by NE, and the effect on the former was more significant than that on the latter(P<0.05). Conclusion: TFH, Que and Isor might decrease the levels of Ca~ 2+ _ i in VSMCs by blocking both voltage-dependent calcium channels (VDC) and receptor-operated calcium channels (ROC) in physiological or pathological state, which may be one of the important mechanisms of their hypotensive and protective effects on target organs in patients with hypertension.

关键词： total flavonoids of Hippophae rhamnoides L. spontaneously hypertensive rats Wistar-Kyoto rats vascular smooth muscle cells intracellular free calcium

Antihypertensive effects of total ginsenosides and regulation of the perturbed metabolism of spontaneously hypertensive rats

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Effect of angiotensin 1-converting enzyme inhibitorypeptide from rice dregs protein on antihypertensiveactivity in spontaneously hypertensive rats

第九届全国药物和化学异物代谢学术会议

作者： A Ji-ye~1,WANG Guang-ji~(1*),HAO Hai-ping~1,HUANG Qing~2,LU Yi-hong~2,YAN Bei~1, ZHA Wei-bin~1,GU Sheng-hua~1,ZHANG Ying~1,LIU Lin-sheng~1,CAO Bei~1,SHI Jian~1,LI Meng-jie~1, WANG Xin-wen~1,ZHAO Chun-yan~1,ZHANG Mei~2,FAN Xia-lei~2 1 Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009, Jiangsu,China 2 Jiangsu Institute for Food and Drug Control,Nanjing 210008,Jiangsu,China

AIM:Essential hypertension is inherently associated with metabolic disorders,and its pathogenesis remains poorly *** of the metabolic perturbation of hypertension and the regulation of this perturbed metabolism using therapeutic agents can extend our insight into the pathogenesis of this ***:We used gas chromatography mass spectrometry and principal component analysis to profile the metabolic phenotype of hypertension in spontaneously hypertensive rats(SHR) and studied the regulatory effect of total ginsenosides(TG) and four typical antihypertensive agents on in vivo ***:The five agents yielded different hypotensive effects and distinct regulation patterns on the perturbed metabolism that occurs in ***,amlodipine,and terazosin efficiently depressed systolic blood pressure(SP) but had a negligible regulatory effect on the perturbed metabolism of SHR,even after the remission of hypertension for 8 *** finding suggests that hypertension may not be the cause of the metabolism perturbation observed in these *** contrast,TG gradually and markedly regulated the perturbed metabolism, and led to a mild but sustained depression of SP up to 2 weeks after the cessation of ***, TG downregulated free fatty acids(FFA) toward normal levels;the elevation of FFA correlates with blood pressure,in both animals and ***:These results suggest that TG may act as a special antihypertensive agent that regulates the perturbed metabolism of hypertension.

关键词： metabonomics hypertension total ginsenosides spontaneously hypertensive rats free fatty acids

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1H NMR-based metabonomic study on urine from Danhong injection treated spontaneously hypertensive rats

中国食品科学技术学会第五届年会暨第四届东西方食品业高层...

作者： Qihe Chen PhD Guodong Xuan PhD Mingliang Fu Guoqing He PhD Wei Wang MB Hongbo Zhang MB Hui Ruan PhD (Department of Food Science and Nutrition,Zhejiang University.268 Kaixuan Road.Hangzhou,Zhejiang,China 310029)

＜正＞Background:Angiotensin Ⅰ-converting enzyme（ACE）inhibitory peptide has good effect on blood pressure ***,research to find and develop safer,effective and economical ACE inhibitors is necessary for the prevention and remedy of *** food-derived ACE inhibitory peptides isolated from food or from enzymatic digestion of food proteins are the sate and efficient substitution for human health Objective:To investigate the effect of rice dreg enzymatic hydrolysates as an anti-hypertensive in vivo with spontaneous hypertension rats（SHRs）.Design:The once-oral adrninistration experiments with rice dreg hydrolysates peptide （RDHP） in different doses were conducted using 6 weeks old spontaneous hypertension rats as the test *** five SHRs were randomized into five groups according to blood-pressure *** group A is blank control group,the group B positive control group（Captopril）,the group C（1.0 mg/kg）,the group D（RDHP 10 mg/kg）and group E （RDHP 50 mg/kg）.The administration approach is to fill in stomach by *** blood pressure value was observed for each *** long term oral administration design was conducted for one *** four SHRs were randomized into 3 *** first group is the blank control,the second group is low dose （RDHP 10 mg/kg） and the third group is high dose （RDHP 20 mg/kg）.In administration period,blood pressure was measured for once a week Outcomes:The once-oral administration animal experiments showed that the blood pressure of SHR drop was 11mmHg,17 mmHg,26.00 mmHg,17 mmHg at a dosage of 1 mg/kg,10 mg/kg,50 mg/kg hydrolysates and 1mg/kg captopril,respectively,after 1h *** results of long-term oral administration indicated that the blood pressure drop was 17 mmHg,26 mmHg in 10 mg/kg and 20 mg/kg,respectively after 30 days *** not only prornoted the growth of SHR,but also had no adverse effect on heart ***:The present study indicated the inhibitory peptides fr

关键词： rice dreg protein ACE inhibitor antihypertension spontaneously hypertensive rats

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Protective effect of sodium ferulate on cardiac hypertrophy in spontaneously hypertensive rats

2019中国生理学会学术年会暨张锡钧基金第十五届全国青...

作者：李静 JIANG Ping WU Guixia College of Basic Medicine Xinjiang Medical University

AIM To investigate the effect of Danhong injection on the urine metabolites of spontaneously hypertensive rats(SHR) by 1 HNMR metabonomics *** 12-weeksage SHR rats were randomly divided into two groups: SHR group and Danhong injection intervention group(DH group).Wister-Kyoto rats of the same age were selected as the control group of normal blood pressure(WKY group), 7 rats in each *** group was treated with DanHong Injection(10 mL/kg), SHR group was treated with the same amount of sterilized saline solution,both of which were injected in the rat’s abdominal cavity according to their weights and continuously administered for 28 *** pressure and heart beat rate of each group rats were checked, the urine was collected for 24 h after medicine *** profile in urine were determined by 1 HNMR metabonomic technique, PLS-DA was used in pattern recognition, OPLSDA correlation coefficient was used to find differences of metabolites components, clustering analysis was done in the *** The metabolites in WKY group, SHR group and DH group could be clearly distinguished, and a total of 11 characteristic metabolites, Citrate, α-ketoglutaric acid, Histidine, Guanidinoacetic acid and Taurine were screened *** main related pathways included Glycolysis and gluconeogenesis, Adipocytokine signal transduction pathway,Arginine and proline metabolism, tricarboxylic acid *** The excretion of various metabolites were regulated by Danhong injection in rat urine, that improve the internal environment and produce protect effect of the body.

关键词： Danhong injection spontaneously hypertensive rats urine metabolites metabonomics

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中国药理学与毒理学杂志 2019年第9期33卷 752-752页

作者： CHEN Pan-pan LI Zhong-li JIN Feng NIE Jing GONG Qi-hai SHI Jing-shan DENG Jiang Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University

OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as *** 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial *** order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were *** The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR ***,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and *** SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.

关键词： sodium ferulate spontaneously hypertensive rats cardiac hypertrophy calcium-sensing receptor