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Aim To investigate the effect of salvianolic acid B (Sal B)on c-Jun N-terminal kinase (JNK)ac-tivation and apoptosis of INS-1 cells induced by inter-mittent high glucose.Methods INS-1 cells were pre-incubated with Sal B for 24 h,followed by exposure to intermittent high glucose (IHG,11.1 mmol·L-1 12 h,33. 3 mmol·L-1 12 h)for 72 h.Cell viability was assessed by MTT assay and cell apoptosis was evalua-ted by flow cytometry.Glucose induced insulin secre-tion capacity and intracellular reactive oxygen species (ROS)contents were measured by enzyme linked im-munosorbent assay (ELISA)and a fluorescent probe DCFH-DA,respectively.Levels of JNK activation and PDX-1 protein expression were determined by Western blot analysis.Results Sal B significantly alleviated IHG-induced cell injury and apoptosis,with glucose induced insulin secretion capacity improved evidently (P<0.05 or P<0.01).Preincubation with Sal B no-tably decreased intracellular ROS and JNK activation in INS-1 cells,while the level of PDX-1 protein was in-creased markedly (P<0.05 or P<0.01 ).Conclu-sion Sal B is capable of ameliorating IHG-induced cell injury and apoptosis in INS-1 cells,which might be derived from suppression of JNK activation and up-regulation of PDX-1 protein expression.
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AIM:To study the effects of sesamin (Ses) on attenuating renal injury in spontaneously hyperten-sive rats (SHR) and its relationship with PI3K/AKT/mTOR signaling pathway.METHODS:Spontaneously hypertensive rats were randomly divided into 4 groups:model (SHR) group, Ses low-dose (80 mg/kg) group, Ses high-dose (160 mg/kg) group and captopril (30 mg/kg) group.Another 7 WKY rats were given 0.5%sodium carboxymethylcellulose ( CMC-Na, the solvent was used to dissolve the drugs) as control group.Meanwhile, the rats in drug treatment groups were given the corresponding drugs.All animals were administered intragastrically once a day, and the blood pressure was measured every 2 weeks before and after the beginning of the administration.After 12 weeks, blood urea nitrogen ( BUN) , serum creatinine ( SCr ) , urine micro-albumin ( U-mAlb ) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD ) were measured.The pathological changes of the renal tissues were observed under microscope with HE and Masson staining.Ap-optotic rate of nephridial tissue was determined by TUNEL method.The protein levels of p-AKT, p-mTOR, 4EBP1, S6K1, Bcl-2 and Bax were detected by Western blot.RESULTS:Ses decreased the diastolic blood pressure of SHR, significantly ameliorated the pathological damage in the nephridial tissues.Compared with model group, Ses was obviously reduced the contents of SCr, BUN, U-mAlb, MDA and apoptotic rate of the kidney, decreased the protein levels of p-AKT, p-mTOR, 4EBP1, S6K1 and Bax, and increased the protein expression of Bcl-2 and SOD activity.CONCLUSION:The protective effects of Ses against renal injury in SHR may be related to decreasing blood pressure, increasing anti-oxidative stress, re-straining apoptosis and inhibiting over-activated PI3K/AKT/mTOR signaling pathway.
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The parabrachial nucleus (PB)is made up of gray matter around the Pons combination(BC),mainly consisting of glutamatergic,GABAergic and enkephalinergic neurons.PB is connected to hypothalamus and basal forebrain through a network of nerve fibers.Specific lesion of the entire parabrachial complex in animals leads to a deep coma.PB also projects to the non-rapid eye movement(NREM)-related regions including the ven-trolateral preoptic,and receives the projections from the parafa-cial zone.Activation of the GABAergic neurons in parafacial zone can promote NREM sleep,which indicates that PB partici-pates in NREM sleep.Furthermore,the lateral PB is actived when rapid eye movement(REM)sleep is deprived.In conclu-sion,PB participates in regulating wakefulness, NREM and REM sleep.This review summarizes the advances in the roles of PB in sleep-wake regulation.
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Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.
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The aim of the present study is to investigate the protective effect of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension (PAH). PAH rats were induced by a single injection of monocrotaline (60 mg x kg(-1), sc) and were administered with chrysin (50 or 100 mg x kg(-1) x d(-1)) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle (RV) to left ventricle (LV) + septum (S) and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expressions of collagen I, collagen III, NADPH oxidase 4 (NOX4) and nuclear factor-kappa B (NF-κB) were analyzed by immunohistochemisty, qPCR and (or) Western blot. The results showed that chrysin treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by chrysin. The expressions of NOX4, NF-κB and MDA contents were obviously decreased, while the T-AOC was significantly increased in right ventricule from PAH rats with chrysin treatment. These results suggest that chrysin ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of NOX4 expression and antioxidant activity, and inhibiting NF-κB expression and collagen accumulation.
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Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-beta1, alpha-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-beta1, AR, alpha-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of alpha-SMA and collagen I induced by TGF-beta1, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-beta1-induced proliferation of fibroblasts, up-regulation of alpha-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.
Subject(s)
Animals , Rats , Airway Remodeling , Aldehyde Reductase , Asthma , Bleomycin , Blotting, Western , Bromodeoxyuridine , Collagen , Diabetic Neuropathies , Fibroblasts , Fibrosis , Flow Cytometry , Gene Expression , Negotiating , Pulmonary Fibrosis , Real-Time Polymerase Chain Reaction , RNA, Messenger , Transforming Growth Factor beta1 , Up-RegulationABSTRACT
The aim of the present study is to investigate the effects of sequoyitol (Seq) on expression of eNOS and NOX4 in aortas of type 2 diabetic rats. Type 2 diabetic rats induced by high fat and high sugar diet and low dose of streptozotocin (STZ, 35 mg x kg(-1)) and were administered Seq (12.5, 25 and 50 mg x kg(-1) x d(-1)) for 6 weeks. The fasting blood glucose (FBG) and body weight were tested. Acetylcholine (Ach) induced endothelium-dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Aortic morphological change was observed with HE staining. The level of serum insulin was measured by radioimmunoassay. The total antioxidative capacity (T-AOC), malondialdehyde (MDA) and NO levels in aortas were determined according to the manufacturer's instructions. In addition, the expressions of eNOS and NOX4 in aortas were measured by immunohistochemisty, real-time PCR or Western blotting. The results showed that Seq significantly decreased FBG and insulin resistance, and improved aortic endothelium-dependent vasorelaxation function. The expressions of NOX4 and MDA content were obviously decreased, while the expression of eNOS, the levels of NO and T-AOC increased significantly in aortas of diabetic rats with Seq treatment. In conclusion, Seq protects against aortic endothelial dysfunction of type 2 diabetic rats through down-regulating expression of NOX4 and up-regulating eNOS expression.
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This study is to observe the effects of sequoyitol on the expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver diseases. The model of high fat and high sugar diet as well as intraperitoneal injection of small dose of streptozotocin (STZ, 35 mg x kg(-1)) induced diabetic rat liver disease was used. After sequoyitol (50, 25 and 12.5 mg x kg(-1)) was administrated for 6 weeks, the contents of blood glucose (BG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), NO and insulin (Ins) were measured, liver p22 phox and p47 phox mRNA content was determined with real-time PCR and the expression of p22 phox and p47 phox protein was examined by Western blotting. In addition, pathological changes in liver were observed with HE staining. Sequoyitol could reduce the content of fasting blood glucose, ALT, AST, Ins and H2O2, restore insulin sensitive index (ISI) and weight, elevate liver tissue T-AOC and NO content, reduce the NADPH oxidase subunit liver tissue p22 phox and p47 phox mRNA and protein expression, as well as ameliorate liver pathologic lesions. The results showed that sequoyitol can ease the type 2 diabetic rat liver oxidative stress by lowering NADPH oxidase expression.
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This study is to observe anti-lipotoxic effect of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet. Thirty-four complex model rats were induced by two-kidney, one-clip method and on high-fat and refined-carbohydrate diet for thirteen weeks. From the fifth week, intragastric administration of sesamin (120, 60 and 30 mg x kg(-1) x d(-1)) lasted for eight weeks. Blood pressure (BP), blood fat (BF), blood glucose (BG), free fatty acids (FFA), insulin (Ins), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined. Pathological changes of pancreas, perirenal fat and liver were semiquantitatively analyzed. In sesamin (120 and 60 mg x kg(-1) x d(-1)) group, it was found that there were decrease of levels of BP, BF, BG, TNF-alpha, IL-6 and FFA, improvement of insulin resistance and glucose tolerance, alleviation of body weight, humid weight of fat, liver and pancreas and their organ index, and reduction of islet cell hyperplasia and amount of lipid droplet vacuoles in lipocyte and hepatocyte. It is implied that sesamin had anti-lipotoxic effect and its mechanism may be closely associated with the amelioration of insulin resistance via reducing lipidoses in hepatocyte and inflammatory adipokines such as TNF-alpha and IL-6.
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Collective preparation for classes is a very effective teaching activity.It can maximize teaching effects,practically raise teacher's teaching enthusiasm for the course and improve teaching quality.Moderator of collective class preparation should be well familiar with the teaching program and content,dig into teaching material,look up for relative information,draw up standard original text then lead and organize whole preparation process for classes from the aspects of introducing teaching objective and content,analyzing teaching material,discussing the new content and progress,analyzing the relative excises,exploring the teaching methods and proposing the questions for discussion.
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AIM: To study the effect of sesamin on expression of inducible nitric oxide synthase(iNOS)and nitrotyrosine(NT)in rat liver tissue with metabolic syndromic hepatic steatosis. METHODS: The rat model of metabolic syndromic hepatic steatosis was induced by operation of two kidneys with one clip(2K1C)and high-fat. The rats taken from that successful model were randomly divided into model group and sesamin(120, 60, and 30 mg·kg~(-1)·d~(-1))groups. In addition, the sham-operated group was set up. The rats in treated group were given sesamin intragastrically everyday for 8 weeks. The levels of blood lipids(TC, TG and FFA)in serum were detected. The activity of SOD and MDA level in the liver homogenate were determined. The expressions of iNOS and NT proteins were detected by Western blotting analysis. The histopathological changes were observed by HE staining in the liver tissues. RESULTS: Compared to model groups, sesamin(120, 60 mg·kg~(-1))significantly inhibited the elevation of serum TC, TG, FFA, and MDA in liver homogenate(P<0.05), and increased the activity of SOD(P<0.05). It also decreased the protein expression of iNOS and NT(P<0.05), and ameliorated the degree of hepatic steatosis. CONCLUSION: Sesamin prevents and cures the metabolic syndromic hepatic steatosis. The mechanism is probably mediated through decreasing the protein expression of iNOS and NT, and alleviating the oxidative stress in addition to regulating the lipid metabolism.
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Aim To explore renoprotective effect of sesamin in metabolic syndrome rats.Methods Metabolic syndrome was induced by high-fat and refined-carbohydrate diet.Sesamin(120,60 and 30 mg?kg-1?d-1)and simvastatin(5 mg?kg-1?d-1)were given to the metabolic syndrome rats at 9th week,which lasted for 16 weeks.After 24 weeks,body weight,left kidney humid weight,blood sugar,blood fat,systolic blood pressure,renal function,and indexes of oxygenation and antioxygenation for renal cortex were measured.Pathological changes,collagen deposition and iNOS protein and nitrotyrosine expression of kidney were observed by HE-staining,Masson-staining and immunohistochemical method,respectively.Results Decreasein blood sugar,blood fat,blood pressure,and MDA,?OH and NO2-/NO3-in renal cortex was obviously observed in high-and middle-dosage sesamin groups;activities of T-SOD,CAT and GSH-Px in renal cortex was increased;expression of iNOS protein and nitrotyrosine in kidney was down-regulated;inflammatory cell infiltration and collagen deposition in renal glomerulus and renal interstitium were improved;glomerular sclerosis and renal interstitial fibrosis were reversed;renal function was ameliorated.Conclusion Sesamin played a role in antioxidative stress and had protective effect upon renal diseases in metabolic syndrome rats.
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AIM: To study the renoprotective and synergistic effects of sesamin in combination with vitamin E on nephropathy in rats with the metabolic syndrome.METHODS: Nephropathy of metabolic syndrome in rats was induced by high-fat and high-carbohydrate diet.Sesamin(30 mg?kg-1?d-1),sesamin +vitamin E [(15+20) mg?kg-1?d-1),sesamin +vitamin E(30+20) mg?kg-1?d-1] and vitamin E(20 mg?kg-1?d-1) were given to rats with metabolic syndrome at 9th week and lasted for 16 weeks.After 24 weeks,the body weight,left kidney humid weight,blood glucose(BG),blood lipids(BL),systolic blood pressure(SBP), renal function,and indexes of oxygenation and antioxygenation for renal cortex were measured.Pathological changes,collagen deposition and iNOS protein and nitrotyrosine expression of kidney were observed by HE-stain,Masson-stain and immunohistochemical method,respectively.RESULTS:(1)In high-fat and refined-sugar diet group(HFS): the levels of BG,BL,SBP,and MDA,OH and NO2-/NO3-in renal cortex were increased;the activities of T-SOD, CAT and GSH-Px in renal cortex were decreased;the expressions of iNOS protein and nitrotyrosine in kidney were up-regulated;the inflammatory cell infiltration and collagen deposition in renal glomerulus and renal interstitium were severe;the glomerular sclerosis and renal interstitial fibrosis were obvious;the renal function was deteriorated.(2)In sesamin +vitamin E [(30+20) mg?kg-1?d-1] group: the decreases in BG,BL,SBP,MDA,OH-and NO2/NO3-in renal cortex were obviously observed;the activities of T-SOD,CAT and GSH-Px in renal cortex were increased;the expressions of iNOS protein and nitrotyrosine in kidney were down-regulated;the inflammatory cell infiltration and collagen deposition in renal glomerulus and renal interstitium were improved;the glomerular sclerosis and renal interstitial fibrosis were reversed;the renal function was ameliorated.The therapeutic effect of sesamin +vitamin E[ (30+20) mg?kg-1?d-1] surpassed that of using sesamin or vitamin E alone(P
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AIM: To investigate effects of salvia miltiorrhiza injection on acute myocardial ischemia and hemorheology. METHODS: The acute myocardial ischemia model and blood stasis model were established with high dose adrenaline subcutaneous injection and being socked in ice water. The effect of salvia miltiorrhiza injection on the electrocardiogram J point and T ware of acute myocardial ischemia and the hemorheology of rat blood stasis model were observed. RESULTS: As compared with model groups, middle and high dose groups of salvia miltiorrhiza injection could obviously inhibit the rising of J point and T wave of the ischemic electrocardiogram, all dose groups of salvia miltiorrhiza injection could prevent the ascending of blood viscosity and fibrinogen and hematocrit. CONCLUSION: salvia miltiorrhiza injection can effectively decrease blood viscosity and improve circulatation of coronary artery, and protect ischemic myocardium.
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AIM:To explore the effects of sesamin on blood glucose,blood lipids and vascular cell adhesion molecule-1(VCAM-1)protein expression of aorta in rats with metabolic syndrome.METHODS:A high-fat,refined-carbohydrate diet was given to rats to induce metabolic syndrome for 24 weeks.Sesamin(120,60,30 mg?kg-1?d-1)were given to the metabolic syndrome rats at the ninth week by intragastric administration,which were lasted for 16 weeks.Then,the body weight and abdominal fat of all rats were weighed and the levels of blood lipid,blood glucose,the total anti-oxidation capacity(T-AOC)and the hydrogen peroxide concentration in the serum were determined.In addition,the pathological change and the VCAM-1 protein expression of aorta were observed by H-E staining and immunohistochemical method respectively.RESULTS:Compared with those in model group,the body weight and abdominal fat of sesamin(120,60 mg?kg-1?d-1)groups were obviously decreased,the levels of serum TG,TC,LDL-C and blood glucose were markedly decreased and the level of HDL-C was increased.The VCAM-1 protein expression of aorta was depressed.The pathological change was improved;The T-AOC and hydrogen peroxide concentrations of serum and aorta were decreased.CONCLUSION:Sesamin can obviously descrease the levels of blood lipid,blood glucose and depress the VCAM-1 protein expression of aorta,improve the pathological change of aorta and protect against the progression of atherosclerosis.
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AIM:To explore the effect of sesamin on blood fat,blood glucose and vascular remodeling in rats fed with high-fat,refined-sugar diet.METHODS:A high-fat,refined-sugar diet was given to rats for 24 weeks.Sesamin(120,60,30 mg?kg-1?d-1)was given by intragastric administration to the rats at 9th week,which lasted for 16 weeks.After 24 weeks,blood glucose,blood fat,blood pressure,activity of total anti-oxidation capacity(T-AOC)and concentration of hydrogen peroxide in serum and aorta were determined.Changes of histology and collagen fibers were observed in aorta by HE and Masson' staining,respectively.Immunohistochemical method was used to examine iNOS protein expression in aorta.In mesenteric arteries,media thickness(M),luminal radius(L)and ratio of media to lumen(M/L)were measured.RESULTS:Compared to model group,sesamin(120,60 mg?kg-1?d-1)obviously decreased the levels of blood glucose,blood fat,blood pressure and concentration of hydrogen peroxide in serum and aorta.Sesamin also markedly enhanced the activity of T-AOC in serum and aorta and reduced collagen deposition and iNOS protein expression in the vascular wall.In addition,proliferation of intima and vascular smooth muscle cells were improved.In mesenteric arteries,sesamin lessened M and M/L and increased L of mesenteric arteries.CONCLUSION:Sesamin ameliorates disorders of glucose and lipid metabolism and inhibits vascular remodeling in rats caused by chronic high-fat,refined-sugar diet.
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AIM: Two models of experimental myocardial ischemia were set up to observe the protection of Danshen glucose injection against ischemia in rats. METHODS: Models of experimental acute myocardial ischemia were made by ligature or medication (pituitrin) to check the indices of ECG, hemodynamics, and morphology. RESULTS: A dosage of Danshen glucose injection 4.0 g/kg, 8.0 g/kg was given to rats by intravenous injection; the rats had undergone a thirty-minute ligatute of coronary left anterior descending branch, and used as a model of ischemic reperfusion. The observations showed that Danshen glucose injection exerted a recovery effect on heart rate, blood pressure, internal pressure of left ventricule and its peak/trough rate (?dp/dt max ), and ST segment (electrocardiogram). The injection markedly reduced the myocardial infarct size of the coronary-ligatured rats. The injection benefited the rats with pituitrin (iv) induced acute myocardial ischemia to reverse and T-wave fall. CONCLUSION: Danshen glucose injection has a protective and therapeutic action on the experimental myocardial ischemia of rats.
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Aim To investigate the difference of aortic function between renal hypertension rat(2K1C) and renal hypertensive-hyperlipidemia rat(RHHR).Methods Animals were divided into 3 groups: the sham-operated group,RHHR and 2K1C model groups.The vascular function test was performed in vitro.The response of aortic ring to phenylephrine(PE),acetylcholine(ACh) and sodium nitroprusside(SNP) was measured.Then aortic ring was incubated with nitricoxide synthase inhibitor N-nitro-L-arginine-methyl-ester(L-NAME) and its response to Ach was observed.Results The contraction in response to PE was augmented in the two model groups.ACh-induced vasorelaxation was reduced in both model groups,and such relaxation was more depressed in RHHR than that in 2K1C.The ability of relaxation evoked by NO was impaired in two model groups.SNP elicited complete relaxation in three groups,but the sensitivity to SNP was more decreased in RHHR than those in sham-operated and 2K1C groups.Conclusion These findings suggest that the vasodilation function of aorta is more impaired in RHHR than that in 2K1C group.The decrease in utilization of vascular smooth muscle to NO induced by hyperlipidemia may contribute to the main cause.