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Objective To investigate therapeutic effects of phlorizin on the early stage of diabetic retinopathy(DR)in diabetic db/db mice.Methods The 24 db/db male mice were divided into 3 groups of phlorizin-treated diabetic group(20mg/kg of phlorizin by intragastric gavage)(DMT,n =8),diabetic group(normal saline solution by intragastric gavage)(DM,n=8),with C57BLKS/J db/ m mice as the control group(CC,n=8)for ten weeks.After ten weeks,all mice were sacrificed and the retina was isolated.The specimen was embedded in paraffin wax and sliced.The sections were dyed with Sudan red and observed for retinal morphological change.Meanwhile,the expressions of GSK-3β and phospho-GSK-3β in retinas were determined by western blot.Results During the study,the CC group showed good condition.The DM group featured with polydipsia,polyphagia and a rapid increase of body weight.Phlorizin-treated diabetic mice displayed much better than the DM group.Compared with CC group,DM group showed cells proliferation in capillary endothelia and obvious thickening in basement membrane.After administration of phlorizin,the vascular lesion of central regions was remarkably improved.The expression level of phospho-GSK-3β protein was lower in DM group than in control group(76.2±15.8 vs.255.4 ± 10.7,t =16.30,P＜0.01)and was higher in Phlorizin-treated DM group(188.5±18.4)than in DM group(76.2± 15.8,t=8.05,P＜0.01).Conclusions Phlorizin decreases phospho-GSK-3β3expression in retina in db/db diabetic mice and suppresses the GSK-3βactivity,which leads to the protection of DR.
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<p><b>BACKGROUND</b>Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity. It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase. Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen (PCNA) plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis. Therefore, we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension. And PCNA might be involved in this process.</p><p><b>METHODS</b>Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group. Systolic blood pressure was recorded weekly. After four weeks of treatment, morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy. The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry, real time quantitative PCR, and Western blotting.</p><p><b>RESULTS</b>After 4-week treatment, there was no significant difference in systolic blood pressure compared with the control group, but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment.</p><p><b>CONCLUSIONS</b>These results suggest that ouabain induces alterations in the brain structure, and this effect is independent of blood pressure. PCNA might be involved in the repair process of ouabain-induced brain damage.</p>
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Animals , Male , Rats , Blood Pressure , Hypertension , Drug Therapy , Metabolism , Immunohistochemistry , Ouabain , Therapeutic Uses , Proliferating Cell Nuclear Antigen , Metabolism , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Sodium-Potassium-Exchanging ATPase , MetabolismABSTRACT
Objective To investigate the effect of hypertension on the large artery elasticity index (C1),the small artery elasticity index (C2) and the medial structure of the ascending aorta as well as the relationship between artery elasticity and the medial structure of the ascending aorta.Methods Sixty patients with CHD receiving coronary artery bypass graft surgery at our hospital were divided into two groups:30 patients in the hypertension group and 30 patients in the non-hypertension group.C1 and C2 were measured using the CVProfilor DO-2020 system.Sections of tissues taken from the anterior wall of the ascending aorta during the surgery were subjected to Masson's trichrome staining for the detection of vascular smooth muscle and collagen fibers and Weigert's resorcin-fuchsin staining for the detection of elastic fibers.The relative areas of vascular smooth muscle fibers,collagen fibers and elastic fibers of the ascending aorta were measured by a computer image analysis system under the light microscope.The linear correlations of C1 and C2 with the medial structure of the ascending aorta were analyzed.Results C1 in the non hypertension group was higher than that in thehypertensiongroup[11.9±1.8 (ml/mmHg×10) w 13.1±2.5 (ml/mmHg×10),t 2.22,P ＜0.05].In the media of the ascending aorta,the relative content of collagen fibers was higher,while the relative content of elastic fibers was lower in the hypertension group than in the non-hypertension group [(46.0±3.8)％ w (42.2±3.0)％,(17.5±3.5)％ vs.(19.3 2.7)％,respectively,t=4.24 and 2.20,P＜0.01 or 0.05].C1 was positively correlated with the relative content of elastic fibers but negatively correlated with the relative content of collagen fibers in both groups (r=0.52 and 0.39,respectively,P＜0.05 or 0.01).Conclusions The main pathogenic basis of hypertension-induced decline in arterial elasticity in CHD patients is increased collagen fibers and reduced elastic fibers with disorganization of the two types of components.C1 may accurately reflect the effect of hypertension on medial collagen fibers and elastic fibers in the ascending aorta.
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Objective To observe the effects of phlorizin on aorta of diabetes db/db mice and to explore its mechanism.Methods Sixteen diabetes db/db mice were randomized into two groups:untreated diabetic group (DM group) and diabetic group treated by phlorizin(DMT group) with eight db/m mice as normal control group(CC group).Phlorizin (20 mg/kg) was given in normal saline solution intragastrically to the mice of the DMT group for 10 weeks.Mice of the other two groups were given the same amount of saline solution intragastrically for 10 weeks.Animals were weighed weekly.At 10th weekend,all mice were fasted overnight and then sacrificed.Fasting blood was collected,and aortas were dissected.The blood samples were analyzed for fasting blood glucose (FBG),triglycerides (TG),total cholesterol (TC),Serum advanced glycation end products(AGEs)and malondialdehyde (MDA).Aortic tissue were examined microscopically.Results At 10th weekend,the weight (57.53±3.40)g and serum concentration of FBG(31.21±2.16) mmol/L,TG (0.39±0.12) mmol/L,TC(3.15±0.30)mmol/L,AGEs (0.28±0.04) AU/mg and MDA (15.18± 1.60)mol/L in DM group were increased than those in CC group (P＜0.01),and the weight(54.24± 1.28)g,FBG(29.17±1.41) mmol/L,TG(0.26±0.06) mmol/L,TC(2.71±0.26) mmol/L,AGEs (0.24±0.03) AU/mg and MDA(13.46±1.28)mol/L were lowered significantly in DMT group than those in DM group (P＜0.05 or P＜0.01).The severity of aorta damage in DMT group was less than that in DM group.Conclusions Phlorizin can protect the db/db mice from diabetic macrovascular complications,which may be attributed to its decreasing of blood glucose,TG,TC,and AGEs levels,and its antioxidant potential.
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Objective To observe the effect of grape seed proanthocyanidin extract (GSPE) on vascular remodeling in ouabain-induced hypertensive rats.Methods A total of 30 male SpragueDawley rats were randomized into 3 groups:control group (received 0.9％ 1 ml normal saline by intraperitoneal injection and oral gavage in the morning),ouabain treatment group (received 2 mg/kg ouabain by intraperitoneal injection and 0.9 ％ 1 ml normal saline by oral gavage in the morning),and GSPE treatment group (received 2 mg/kg ouabain by intraperitoneal injection and 250 mg Kg 1 d-1 GSPE by oral gavage in the morning).Blood pressure was determined before and 5 weeks after the treatment.The aortas were observed 5 weeks after the treatment.The mRNA and protein levels of nuclear factor-κB (NF-κB p65) and transforming growth factor-β1 (TGF-β1) in rat aorta were detected using real-time PCR and Western blot,respectively.Morphological observations were obtained by Hemotoxylin and Eosin staining and Electron microscope.Results The systolic blood pressure was significantly lower in GSPE treatment group than in ouabain treatment group [(133.6±6.0) mm Hg vs.(146.5±7.9) mm Hg,1 mm Hg=0.133 kPa,P＜0.01].Morphological observation showed that the thickening aortic intimal and structural disorder were found in the ouabain treatment group,and aortic intimal structural integrity were normal in the other two groups.The mRNA and protein levels of NF-κB p65 and TGF-β1 were significantly lower in GSPE treatment group than in the ouabain treatment group (NF-κBp65:2.77±0.58 vs.3.14±0.64,0.73±0.20 vs.0.93±0.21,both P＜0.05; TGF-β1:5.80±0.67 vs.6.09±0.95,0.42±0.14 vs.0.69±0.16,both P＜0.05).Conclusions GSPE may inhibit endogenous ouabain,and delay the process of elevated blood pressure and vascular remodeling by inhibiting NF-κ B p65 and (or) TGF-β3 1 pathways.
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ObjectiveTo elucidate the clinical application value of intravascular ultrasound(IVUS) in assessing intermediate lesions and the relationship between serum levels of fractalkine,CD36 and LP-PLA2and severity of coronary artery atherosclerosis.MethodsOne hundred and twenty patients with unstable angina underwent coronary angiography.Then the patients were divided into two groups:severe lesion group (lumen diameter stenosis greater than 70％,including 40 patients),and the intermediate lesion group lumen diameter stenosis(50％～70％,80 patients).IVUS were performed in all patients to analysis the coronary lesions.Concentrations of CD36,fractalkine and LP-PLA2 were measured by means of ELISA.Results IVUS found that 74％ intermediate lesion patients had soft lipid plaques,while 48％ severe lesion patients had lipid plaques ( P＜0.01 ).Patients with severe lesion had larger plaque burden and vascular remodeling index than those of patients with intermediate lesions(P＜0.05～0.01).There were 59 patients(74％) in the intermediate lesion group underwent PCI.IVUS also found the PCI patients had larger plaque burden and vascular remodeling index.Concentration of CD36 was significantly higher in severe lesion group than that of intermediate lesion group (P＜0.05).ConclusionsIVUS could further clarify the characteristics of the intermediate and severe lesions,and provide guidance for PCI treatment.Plasma CD36 level could be used to predict pathological severity of coronary atherosclerosis.
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Objective To investigate the association between carotid-femoral pulse wave velocity (cfPWV) and composition of the ascending aorta in patients with coronary heart disease (CAD),Methods The study population comprised 60 consecutive CAD patients who underwent coronary artery bypass graft (CABG) surgery in Qilu Hospital of Shandong University.cfPWV vas measured using an automatic device (Complior,Artech,France).A quantitative study was conducted on ascending aorta specimens by histological observation (Masson staining and weigert's resorcin-fuchsin staining) and computer image analysis.Bivariate analyses were performed to study the association between composition of the ascending aortic media and cfPWV.Results cfPWV of the CAD patients was higher (14.2±2.0) m/s than that of the normal subjects.On Masson's-stained specimen slides,disorganization of smooth muscle and focal accumulations of collagen (44.1 ± 3.9)％ were visible alongthe medial aorta of the CAD patients.Weigert's-stained cross sections of the ascending aortic media in CAD patients frequently exhibited focal breakdown or discontinuous segments of elastic fibers(18.4±3.2)％,cfPWV had a positive correlation with relative contents of collagen in the ascending aorta(r=0.68,P＜0.01)and a negative correlation vith relative contents of elastin in the ascending aorta (r=-0.59,P＜0.01),but no relation with relative contents of smooth muscle(r=0.01,P＞0.05).Conclusions The reduced aortic elasticity in CAD patients can be partly ascribed to decreased elastin,increased collagen,and their disorganization.cfPWV can reflect the quantitative changes of collagen and elastin in the ascending aortic media in CAD patients.
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Objective To identify the mechanisms of oral administered rapamycin on the prevention of restenosis after stent implantation with intravascular ultrasound (IVUS) and pathology.Methods Twenty-four New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were given a diet of 1 ％ cholesterol for 8 weeks.Then,the rabbits were divided into three groups:the bare metal stent group(BMS group),the bare metal stent with oral rapamycin group(BMS + RAPA group) and the rapamycin eluting stent group(DES group).Rabbits in the RAPA and BMS + RAPA groups received a daily oral dose of rapamycin(0.5 mg/kg),whereas rabbits in the DES group received no drugs.All the rabbits were euthanized after the 4-week intervention.Serum lipids were measured.IVUS and pathologic studies were performed.The minimal luminal diameter (MLD),external elastic membrane (EEM) area,lumen area (LA),and plaque area(PA),plaque burden(PB) were measured.Mammalian target of rapamycin(mTOR) expression level was examined by immunohistochemistry.Results After the 4-week intervention,there was no significant difference of serum lipid levels among the three groups.IVUS showed that oral administration of rapamycin in the BMS + RAPA groups showed similar effects in reducing PA and PB as the DES group,which all were better than the BMS group.The BMS + RAPA and DES groups showed much more MLD and less lumen reduction,compared with the BMS group( P ＜0.05).Level of mTOR expression of the BMS + RAPA group and DES group was significantly lower than that of BMS group.Conclusions Oral administration of rapamycin demonstrates the same effect in the reduction of plaque burden and stent restenosis as the rapamycin eluting stent.Inhibition of mTOR by rapamycin involves in the stent restenosis.
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Objective To explore the relationship between morphological features of carotid arterial atherosclerosis plaque and various cardiovascular risk factors in the aged.Methods The 321patients who underwent cerebral angiography were classified into two groups:256 patients with carotid arterial atherosclerosis and 65 patients without plaque.The relationships between carotid arterial plaque and cardiovascular risk factors including age,gender,cholesterol(TC),triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol(LDL-C),C-reactive protein(CRP),homocysteine (HCY),hypertension,diabetes,smoking and drinking were analyzed.The relationships between morphological features,including the stenosis degree,surface fairing of plaque,and cardiovascular risk factors were analyzed.After 1 year follow-up,the prospective cardiovascular and cerebrovascular events were analyzed in the two groups.Results Carotid atherosclerosis was connected with cardiovascular risk factors such as TC,LDL-C,uric acid,CRP,hypertension,diabetes,smoking and drinking.Positive correlation was showed between the stenosis degree of carotid artery and age,smoking and diabetes.Closely correlation was showed between surface fairing of carotid arterial plaque and LDL-C,CRP,smoking and diabetes.The stenosis degree of carotid artery only showed positive correlation with cerebrovascular events,but the morphological features of surface fairing of carotid arterial plaque equally showed positive correlations with cerebrovascular events and cardiovascular events.Conclusions The development of carotid arterial atherosclerosis plaque in the aged is closely related to cardiovascular risk factors.Morphological features of carotid arterial plaque may respond the level of general atherosclerosis better than stenosis degree,and it is also in close correlation with cerebrovascular events and cardiovascular events.
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Objective To investigate the changes of capacitive arterial compliance(C1) and oscillatory arterial compliance (C2) in elderly patients with the coronary atherosclerosis and the coronary heart disease (CHD)and to study the association between Gensini Score and C1 or C2.MethodsElderly subjects (160 cases) were divided into three groups according to the results of selective coronary angiography: the normal,the coronary atherosclerosis and the CHD group. C1 and C2 were measured using a DO-2020 cardiovascular profiling instrument.The stenosis severity of coronary artery diseases was assessed using a scoring system called Gensini score. Bivariate analyses were performed to study the association between Gensini Score of coronary artery and each of C1 and C2.Results C2 in the coronary atherosclerosis group was significantly lower than that in the normal group, and higher than in CHD group. C1 had no statistically difference among the three groups. Gensini integral in the coronary atherosclerosis versus the CHD groups were ( 5.4+2.6) vs.( 51.3+ 32.1), respectively (t= 10.574, P＜0.01). Gensini Score in the coronary atherosclerosis group had no relation with C1, and was negtively correlated with C2. ConclusionsC2 is decreased in the early stages of the coronary artery atherosclerosis in elderly patients, and may help the identification of early coronary atherosclerosis.
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0.05) during the experiment. The TC of middle dose GSPE group was marked ly different compared with that of normal group(P