59 results about "Spontaneously hypertensive rat" patented technology

The present invention is based upon the observation that a mutant atrial natriuretic factor (ANF) gene increases stroke latency in spontaneously hypertensive rats-stroke prone (SHRSP). Accordingly, the present invention provides methods using mutant ANF proteins, fragments, analogs, derivatives and homologs of mutant ANF proteins, the nucleic acids encoding these mutant ANF proteins, as well as modulators of ANF for treating or preventing ischemic diseases, in particular ischemic stroke. The invention also relates to methods of diagnosis, prognosis and screening for a disposition for diseases and disorders associated with increased levels of ANF. Pharmaceutical compositions, methods of screening for ANF mutants and ANF modulators with utility for treatment and prevention of ischemic stroke are also provided.

The present invention relates to novel antagonists to a B₁-bradykinin (B₁-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B₁ receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B₁-BK receptors in these two models. B₁-BK antagonists abolished the vasocontraction induced by B₁-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels. The present B₁-antagonists are useful for treating any condition wherein B₁-receptor is expressed, particularly during inflammation, and more particularly wherein B₁-receptor expression results in diabetic vasculopathy, other diabetic symptoms associated with an insulitis and a post-capillary resistance building as a consequence of the presence of a B₁-receptor.

The invention relates to a preparation method of a 2-type diabetic nephropathy model. The method comprises the following steps of: selecting a male SHR (spontaneously hypertensive rat) rat with an age of 6 weeks, wherein the blood pressure of the male SHR rat at birth is normal, and at the time of 4 weeks, the blood pressure begins to rise; after adaptively feeding the SHR rat selected in the step (1) for one week, feeding a high sugar and high fat feed for 2 weeks; detecting the weight, the blood fat, the blood sugar and the insulin concentration and calculating an insulin resistance index evaluated by a steady-state model, wherein the insulin resistance index is not smaller than 3.8, and the high fat and high sugar feed comprises the following components in percentage by weight: 10.0 percent of lard, 20.0 percent of cane sugar, 2.5 percent of cholesterol, 2.0 percent of cholate and 66.5 percent of conventional feed; after fasting the insulin resistant SHR rat for 12 hours, carrying out a small-dose one-time STZ (streptozocin) (35mg/kg) intraperitoneal injection on the SHR rat, wherein the small dose is 35mg/kg; after 72 hours, measuring the random blood sugar; and judging the 2-type diabetic nephropathy model to be successfully prepared if the plasma glucose is not smaller than 16.7mmol/L.

The invention relates to Lactobacillus helveticus H9 and application of the Lactobacillus helveticus H9 to the resistance of hypertension and the prevention of cardiovascular disease. A preparation method comprises the following steps of: isolating strains, identifying the strains, preserving the strains, culturing the strains, preparing a bacterial liquid, preparing fermented milk, and screening a strain with angiotensin-converting enzyme (ACE) inhibitory activity; and further evaluating the influence of Lactobacillus helveticus H9 fermented milk on hypertension (SHR, spontaneously hypertensive rats) and normal blood pressure (WHY rats, Wistar-Kyoto rats). The research shows that strain fermented milk has a better in-vivo antihypertensive effect, has the advantages of long onset time and the like, does not affect blood circulation, and has no adverse effects on the normal blood pressure.

The invention discloses an angiotensin II receptor 1 type polypeptide-vector vaccine and an application thereof, belonging to the field of biotechnology drugs and biologic therapeutics. An angiotensin II receptor 1 type immunogenic peptide containing a first connection locus, a derivant thereof and one or more of carriers are preferably coupled and connected with recombined Qbeta-2aa bacteriophage viruslike particle protein to form an ordered and repeated polypeptide-carrier vaccine. The invention also discloses an application of the vaccine on the aspect of treating primary hypertension. Thevaccine can generate one section of efficient specific immunogenic peptide resisting human angiotensin II receptor 1 type and the antibody of the derivant thereof. RAS (Renin-Angiotensin System) can be effectively prevented from activating, the blood pressure of spontaneously hypertensive rats can be obviously lowered, and the vector vaccine has good function on protecting target organs.

The invention relates to a health care product for assisting blood pressure reduction, provides a method for preparing a health care seaweed product for assisting blood pressure reduction via step-by-step extraction and bioconversion coupling, and belongs to the field of deep processing of ocean foods. The method is carried out by taking high-quality seaweeds as raw materials via an ultrasonic circulation step-by-step extraction process and a bioconversion coupling preparation technology. The preparation method sequentially comprises the following steps: carrying out pretreatment of raw materials, alcohol extraction of mannitol, acid extraction and alcohol precipitation of sodium alginate and fucoidan, bioconversion and ultrafiltration so as to obtain physiological active components for reducing blood pressure; and scientifically blending the active components. According to the method, a large quantity of seafood seaweeds in China are deeply processed and comprehensively utilized so as to obtain five products, namely mannitol, sodium alginate, fucoidan, seaweed dietary fibers and seaweed antihypertensive peptides; and the five products are scientifically blended so as to develop a series of novel functional seaweed products for reducing blood pressure reduction, wherein the series of functional seaweed products have obvious functions of assisting blood pressure reduction. The ACE inhibitory activity IC50 of the seaweed product is within 0.68mg/g to 1.15mg/g, so that the blood pressure of an SHR (Spontaneously Hypertensive Rat) can be obviously lowered (-12.4 mmHg to -17.5mmHg).

The invention relates to a construction and preparation method of a recombinant adeno-associated virus recombinant (rAAV-miRNA-21<*>/rAAV-anti-miRNA-21<*>) that is able to regulate human miRNA-21<*>, more specifically to cloning of hsa-miR-21<*> and its antisense sequence hsa-anti-miR-21<*>, a packaging preparation method of recombinant adeno-associated virus recombinants containing hsa-miR-21<*> and hsa-anti-miR-21<*>, as well as pharmaceutical application of the recombinant adeno-associated virus recombinants. With a length of 21nt, the hsa-miR-21<*> is non-coding RNA. A chemical synthesis method is utilized to construct pAAV-D(+)-miR-21<*> and pAAV-D(+)-anti-miR-21<*> expression plasmids. A three-plasmid calcium phosphate cotransfection method is utilized to prepare target segment-containing recombinant adeno-associated viruses and purify them, wherein the pAAV-D(+)-miR-21<*> can obviously lower the blood pressure level of spontaneously hypertensive rats and improve the heart function simultaneously. Therefore, the hsa-miR-21<*> expression sequence-containing recombinant adeno-associated virus is conformed to have the possibility to be used as a drug for clinical treatment of hypertension and other related diseases.

The invention discloses a gracilaria lemaneiformis antihypertensive peptide and application thereof to preparing antihypertensive drugs and healthcare products. Gracilaria lemaneiformis antihypertensive peptide extract is obtained through enzymolysis and then further separated and purified to obtain the gracilaria lemaneiformis antihypertensive peptide with a specific sequence; the amino acid sequence of the gracilaria lemaneiformis antihypertensive peptide is Phe Gln-Ile-Asn-[Met(O)]-Cys-Ile-Leu-Arg(FQIN[M(O)]CILR), and the molecular weight of the gracilaria lemaneiformis antihypertensive peptide acquired through mass spectrum identification is 1153.43Da. The selected gracilaria lemaneiformis antihypertensive peptide is significant in activity on angiotensin converting enzyme inhibition and can in vitro express temperature, pH, gestro-intestinal digestion and angiotensin converting enzyme (ACE) degradation stability. enzyme kinetics survey shows that the gracilaria lemaneiformis antihypertensive peptide is an ACE non-competitive inhibitor and can achieve good antihypertensive effects in vitro and in vivo of spontaneously hypertensive rats (SHRs), thereby being applicable to hypertensive treatment-related healthcare products and drugs.

The invention relates to a method for obtaining peptides from byproducts of abalone processing; and specifically, the invention relates to anti-oxidation effects and angiotensin I converting enzyme (ACE) inhibitory actions of peptides prepared by separating byproducts of abalone processing, as well as the effects of the peptides for resisting hypertension of spontaneously hypertensive rats. The invention further relates to application of the peptides in preparation of drugs and health-caring foods used for treating spontaneous hypertension. According to the method for obtaining the peptides from the byproducts of abalone processing, the peptides are prepared by the following steps of performing electrodialysis desalination on the byproducts of abalone processing, and then, carrying out ultrafiltration membrane system classification and concentration.

The invention discloses angiotensin converting enzyme (ACE) inhibitory peptide which has specific sequence and is screened from porphyra haitanensis enzymolysis products. The sequence of the polypeptide is Thr-Gly-Ala-Pro-Cys-Arg (TGAPCR), and through mass spectrum identification, the molecular weight of the polypeptide is 603.69 Da. The polypeptide has the characteristics of stable structure, notoxicity, high water solubility and the like; and through in-vitro high-performance liquid chromatography (HPLC) identification, the polypeptide has low IC50. Significant effect of reducing the systolic pressure of spontaneously hypertensive rats in vivo is achieved; and the diastolic pressure can be reduced for a long time. The ACE inhibitory peptide with specific sequence can be applied to development of an ACE inhibitor and also can be applied to health-care products and medicine products related to hypertensive therapy.

The invention discloses a vascular smooth muscle L type calcium ion channel immunogenic peptide and application thereof, and belongs to the field of biotechnology and medicine. The immunogenic peptide has the following amino acid sequence: CGGPAEEDPS, CPAEEDPS, PAEEDPSGGC or PAEEDPSC, preferably CPAEEDPS. The vascular smooth muscle L type calcium ion channel immunogenic peptide containing a first binding site is coupled and combined with one or more carriers, preferably recombinant Qbeta-2aa phage virus-like particle protein to form ordered and repeated polypeptide-carrier vaccine. The invention discloses application of the vaccine to treatment of primary hypertension. The vaccine can produce high-efficiency specific antibody against the vascular smooth muscle L type calcium ion channel immunogenic peptide. The antibody can be used for effectively obstructing an L type calcium ion channel, so that the blood pressure of a spontaneously hypertensive rat can be obviously reduced.

The invention relates to the technical field of medicament, and provides an animal model of hypertension and a construction method and application of the animal model. The animal model of hypertensioncan be used for studying pathogenesis of the hypertension and rules of occurrence and development of complications. The construction method includes: on the basis of a spontaneously hypertensive rat,feeding high-sugar and high-fat diets to the model rat, wherein every high-sugar and high-fat diet comprises, by weight, 47.9-49 parts of normal feed, 2-5 parts of cholesterol, 20-25 parts of streptozotocin, 20-25 parts of lard oil, 0.1-5 parts of sodium tauroglycocholate and 10-15 parts of yolk powder; after feeding the rat for 12 weeks, constructing a hypertensive rat model. Biochemical criterions of the constructed hypertensive rat model include systolic pressure, diastolic pressure, blood glucose and blood fat, and blood fat inspection indexes include serum total cholesterol, triacylglycerol, high-density lipoprotein and low-density lipoprotein. The construction method of the animal model is simple to operate, convenient to control and high in model forming rate.

The invention discloses an intermittent preparation method of camellia meal protein antihypertensive peptide. The method comprises the steps: (1) preparing camellia meal protein solutions with the mass concentration of 3.0-6.0 percent by using camellia meal protein with low denaturalization; (2) performing enzymolysis on mixed enzyme of alkaline protease, flavourzyme and trypsase; (3) performing enzymolysis on neutral protease and papain; (4) performing enzymolysis on acid protease to obtain crude enzyme fluid; (5) performing flash evaporation and inactivation; (6) standing and centrifuging; (7) performing vacuum condensation on supernate at low temperature; (8) performing equilibrium dialysis desalination processing on the supernate; (9) filtering by using an ultrafiltration membrane, gathering filtering liquid, freezing and drying to obtain the camellia meal protein antihypertensive peptide. The camellia meal protein antihypertensive peptide prepared by using the intermittent preparation method has ash content of less than 1.0 wt%, protein recovery rate of more than or equal to 93.0 wt% and ACE inhibition rate of more than 90.0 percent, and has an obvious antihypertensive effect on spontaneously hypertensive rats (SHR).

The invention provides application of salvianolate in preparation of kidney protective agent drugs. A study on effects of injection-use salvianolate on acute myocardial perfusion in acute myocardial infarction direct PCI (percutaneous coronary intervention) and prognosis founds that: subjects using the injection-use salvianolate, compared with other group subjects, after use of a contrast agent, may not have severe kidney injuries, and the injection-use salvianolate has a kidney protective effect. The invention also provides the application of magnesium lithospermate B in preparation of the kidney protective agent drugs. Effects of the magnesium lithospermate B on kidney microcirculation and overall hemorheology are studied through use of spontaneously hypertensive rats. Experiments prove that the magnesium lithospermate B in physiological and pathological states both can dose-dependently improve kidney cortex microcirculation, and show that the kidney protective effect of the magnesium lithospermate B is realized through direct improvement of the kidney microcirculation, so that the salvianolate and the magnesium lithospermate B can be used for preparation of the drugs for the prevention and treatment of the kidney injures caused by the contrast agent. The application of the salvianolate in preparation of the kidney protective agent drugs has great clinical application value.

The invention relates to a traditional Chinese medicine composition for controlling hypertension and protecting hypertension target organ against damage, and the traditional Chinese medicine composition is prepared from the following raw material medicines: rhizoma chuanxiong, bupleurum, coptis root, notopterygium, radix saposhnikoviae, prunella spike, cyathula root, polygonatum, concha haliotidis, fried radix scutellariae and herba taxilli. The invention also provides the application of the traditional Chinese medicine composition. The advantages of the traditional Chinese medicine composition are that: the traditional Chinese medicine composition can significantly improve blood pressure indexes of pre hypertension patients, significantly reduces systolic pressure and diastolic pressure level of spontaneously hypertensive rats (SHR), and more important, has significant protective effect against target organ damage in heart, brain and kidney. The traditional Chinese medicine composition used in hypertension early intervention can not only delay the process of hypertension, more important, has the protective effect against target organ damage in hypertension, can be clinically and widely popularized, delays target organ damage, and improves the life quality of the patients.

The invention discloses an application of des-O-methyllasiodiplodin in preparation of a medicament for treating hypertension. Experimental studies show that the des-O-methyllasiodiplodin can well reduce caudal arterial blood pressure, central aortic systolic blood pressure, central aortic diastolic blood pressure, central aortic mean blood pressure and pulse wave velocity of spontaneously hypertensive rats (SHR), improve the artery elastic function, reduce the aortic media thickness and vascular wall collagen fibers and increase the inside diameters of blood vessels, and has a good effect of preventing and treating the hypertension. Obvious adverse response is avoided in the experimental process, and the des-O-methyllasiodiplodin is expected to be developed into a new-generation safe and effective medicament for preventing and treating the hypertension.

The invention discloses a method for measuring the concentration of 7 blood inflow ingredients in an eucommia extract. The method comprises the following steps: firstly preparing a standard control solution by using geniposidic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, pinoresinol diglucoside and terpineol monoglucoside; preparing an internal standard solution by using puerarin; then establishing an analysis method for simultaneous measuring the concentration of 7 ingredients in the eucommia extract in rat plasma by using an HPLC-ESI-MS/MS analysis; and the result shows that the measurement method disclosed by the invention has the advantages of wide linear range, high sensitivity and low limit of quantification, and can be used for accurately and reliably measuring the concentration of the 7 ingredients in the eucommia extract in the rat plasma extracted at 15 different time points after a spontaneously hypertensive rat is gavaged with the eucommia extract at the same time, and can be used for providing a technical support for the researches on the pharmacokinetic characteristics of the 7 ingredients in the eucommia extract.

The invention discloses a compound capable of reducing blood pressure and relaxing blood vessels and application of the compound. The compound has a structure as shown in a formula I which is described in the specification, and can be synthesized and produced on a large scale as a monomeric compound with a clear chemical structure. Experiments prove that arterial blood pressure of spontaneously hypertensive rats can be effectively reduced and the mesenteric microarterial blood vessels of the rats can be relaxed by singly giving the compound (Kanglexin) disclosed by the invention, and the effect is remarkable. The compound disclosed by the invention can be prepared into tablets, powder, capsules, granules, suspensions, injections and the like together with pharmaceutically acceptable carriers, and can be used for relaxing blood vessels and reducing blood pressure in an independent administration mode or a combined treatment mode. The invention provides a new technical means for the treatment of hypertension.

This invention relates to a novel gene that shows tissue specific expression and increased expression in a low calcium concentration medium. Low renin hypertension is characterized by decreased levels of serum ionized calcium in the presence of increased levels of parathyroid hormone. It is hypothesized that hypertensive factor(s) are co-secreted with PTH in SHR, a model of low renin hypertension, the parathyroid hypertensive factor being one of them. As a negative calcium balance is present in spontaneously hypertensive rats (SHR), we searched for gene(s) involved in this dysregulation. A cDNA library was constructed from the SHR parathyroid gland which is a key regulator of serum ionized calcium. From 7 overlapping DNA fragments, a 1100-bp novel cDNA containing an open reading frame of 224 codons was reconstituted. This novel gene, named HCaRG (Hypertension-related, Calcium-regulated Gene), was negatively regulated by extracellular calcium concentration and its basal mRNA levels were higher in hypertensive animals. The deduced protein showed no transmembrane domain, 67% a helix content, a mutated calcium-binding site (EF-hand motif), 4 putative ‘leucine zipper’ motifs and a nuclear receptor-binding domain. At the subcellular level, HCaRG had a nuclear localization. We cloned the human homolog of this gene. Sequence comparison revealed 80% homology between rats and humans at the nucleotide and amino acid sequences. Tissue distribution showed a preponderance in the heart, stomach, jejunum, kidney (tubular fraction), liver and adrenal gland (mainly in the medulla). HCaRG mRNA was significantly more expressed in adult than in fetal organs, and its levels were decreased in tumors and cancerous cell lines. We observed that after 60-min ischemia followed by reperfusion, HCaRG mRNA declined rapidly in contrast with an increase in c-myc mRNA. Its levels then rose steadily to exceed baseline at 48 h of reperfusion. HEK293 cells stably transfected with HCaRG exhibited much lower proliferation, as shown by cell count and 3 H-thymidine incorporation. Taken together, our results suggest that HCaRG is a nuclear protein potentially involved in the control of cell proliferation.