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Objective To observe the effect of external recombinant human basic fibroblast growth factor (rh-bFGF) on the skin and muscles.Methods 40 BALB/c mice of 6 weeks were randomly divided into skin and muscle groups.The skin group was randomly divided into group A and group B.The skin group was injected with 100U rh-bFGF and the same dose of saline in the chin.The muscle groups were randomly divided into C,D,E,and F,and the muscle group was injected into the left calf muscle in order of 200,400,800U rh-bFGF and the same dose of normal saline.The materal was taken at week 8.HE staining was used to observe the submental tissue and muscle fiber morphology.Two groups of muscle fibers,collagen and fibrous tissue were detected by trichrome stain.Immunohistochemistry was used to determine the blood vessel density of the chin and gastrocnemius.Results In week 8,10 mice in group A had a mass in the lower jaw,and the gastrocnemius of the groups C and D showed hypertrophy.Group A showed the thickness of epidermis,dermal papillary layer and mucosa,hair follicle and blood vessel quantity,glandular cavity,collagen and fiber content were sigificantly greater than that of group B (P＜0.05).In the groups C,D and E,the gastrocnemius muscle was significantly thicker than that of group F,and the thickening of group D was the most obvious (P＜0.05),and the contents of collagen and fiber in the groups C,D and E were significantly higher than that in group F.Conclusions Subcutaneous injection of rh-bFGF leads to submental skin thickening,vascular hyperplasia,increased diameter of hair follicle and higher collagen and fiber contents;intramuscular injection of it may induce the muscular hypertrophy and vascular proliferation.
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Objective To examine the association of arteriovenous fistula (AVF) blood flow (Qa) dynamics with inflammation state and its effect on cardiovascular diseases (CVD) in maintenance hemodialysis (MHD) patients.Methods Thirty MHD patients with AVF and twelve healthy people were enrolled in the study.Qa and cardiac output (CO) were measured by Transonic Hemodialysis Monitor HD 02.In MHD patients,pre-dialysis blood samples were taken before Qa monitoring.High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidimetry (Kyoma,Japan).Inflammatory factors IL-2,IL-6,IL-10,TNF were measured by Cytometric Bead Array (BDTM).Cardiovascular diseases morbidity was monitored prospectively within nineteen months follow-up period.Results There were no significant differences in age and sex between MHD patients and healthy people.The serum IL-6,IL-10,TNF and hsCRP were significantly higher in MHD patients than those in healthy controls [2.38 (1.86-4.69) vs 1.14 (0.27-1.18) ng/L,P＜0.01; 1.47 (1.19-2.10) vs 1.04 (0.00-1.23) ng/L,P＜0.01; 1.33 (1.05-1.56) vs 0.54 (0.00-1.24) ng/L,P＜0.05; 4.90 (1.58-7.45) vs 1.50 (0.63-1.90) mg/L,P=0.01].During the follow-up period,6 patients (20.0％) developed at least one episode of cardiovascular event.Qa,serum IL-6 and hsCRP levels were significantly higher in patients with CVD as compared to those without CVD [(1120±192) vs (893±189) ml/min,P＜0.05; 4.86 (2.96-7.85) vs 2.20 (1.80-3.10) ng/L,P＜ 0.01;11.75 (3.83-31.53) vs 4.45 (1.05-6.68) mg/L,P＜0.05].Binary Logistic regression analysis demonstrated that serum IL-6 was an independent and stronger risk factor for CVD morbidity [HR=1.943,95％CI (1.110-3.402),P=0.02].Spearman rank correlation analysis and liner regression analysis showed that Qa was positively correlated with serum IL-6 (β=0.492,P＜0.01).Path analysis suggested that Qa contributed to CVD mortality via the increase of serum IL-6.Conclusions AVF blood flow monitoring is important for MHD patients.IL-6 is an independent risk factor of CVD in MHD patients.AVF blood flow increases cardiovascular diseases morbidity in MHD patients via its promotion of IL-6 production.
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OBJECTIVE:To investigate the effects of calcium dobesilate on the ultrastructure of glomerular basement membrane(GBM)in diabetic rats.METHODS:30rats underwent unilateral nephrectomy,of whom,10were assigned to the normal control group(group NC),another20were induced to diabetic models(DM)by intraperitoneal injection of1%STZ,the models which have finished were divided into DM control group and calcium dobesilate group(group DD),each group admin?istered with distilled water and calcium dobesilate respectively,12weeks later,the change in the ultrastructure of kidneys and endogenous creatinine clearance rate(CrCl)in each group were observed.RESULTS:After12weeks,endogenous CrCl in group DD was significantly higher than that in group DM;Electron microscope showed that thickening of glomerular capillary basement membrane in group DD was less than that in group DM.CONCLUSION:Calcium dobesilate could improve the ul?trastructure in kidney of diabetic rats,prevent GBM thickening,and protect filtration barrier of renal glomerulus.
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To observe the effects of calcium dobesilate on the expression of glomerular tissue inhibitor of metalloproteinase 1 (TIMP1), collagen Ⅳ, and ultrastructure of glomerular basement membrane in diabetic rats, rats model of diabetes was established by unilateral nephrectomy and intraperitoneal injection of 1% STZ (55 mg/kg), and rats were administered calcium dobesilate 100 mg/kg (DD group) or distilled water (DM group) respectively. 12 weeks later, the changes in the renal ultrastructure and creatinine clearance rate (Ccr) were examined in each group. The expression of glomerular TIMP1 and collagen Ⅳ were studied by immunohistochemical staining. Our results showed that after 12 weeks, the Ccr in DD group increased and was significantly higher than that in DM group. Electron microscopy showed that thickness of glomerular capillary basement membrane (GBM) in Group DD was less than that of DM group. No hyperplasia of collagen fibers was found, and the distance between the holes of endothelial cells in DD group was not as even as that in the normal group, but more even than that of DM group, and podocyte processes was still in order. Immunohistochemical staining of glomeruli showed that expression of TIMP1 and collagen Ⅳ in DD group were significantly less than those of DM group DM. It is concluded that calcium dobesilate can improve diabetic nephropathy by inhibiting the over- accumulation of collagen Ⅳ and calcium dobesilate may also contribute to diabetes by inhibiting the expression of TIMP1.
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The role of HO-1 inducer, hemin, in chronic renal failure (CRF) rats and its possible mechanism of action was studied. 5/6 subtotal nephrectomy was performed to establish chronic renal failure model. Rats were randomly assigned to 4 groups: sham-operated group, CRF group, ferrous gluconate group and hemin group. At the 10th week after operation, serum creatinine, BUN, RBC, HGB and HCT were measured. Renal pathologic changes were observed. RT-PCR and immunohistochemistry were used to detect the expression and distribution of HO-1. RT-PCR and radioimmunoassay was used to determine the expression of ET-1 in the kidney and plasma. The results showed that as compared with CRF group, serum creatinine and BUN in hemin group were reduced significantly and nephrogenic anemia was improved markedly. Glomerular mesangial proliferation and interstitial lesion were also ameliorated significantly. Hemin not only increased the expression of HO-1 but also reduced the expression of ET-1 in the kidney. The level of ET-1 protein in the plasma was also reduced after hemin treatment. Most of these indexes were not obviously changed in ferrous gluconate group. It was suggested that through inducing the expression of HO-1 and reducing the level of ET-1 in the kidney and plasma, hemin plays an important protective role in 5/6 subtotal nephrectomized rats.
Subject(s)
Animals , Male , Rats , Endothelin-1 , Genetics , Heme Oxygenase-1 , Genetics , Hemin , Pharmacology , Kidney , Pathology , Kidney Failure, Chronic , Pathology , Nephrectomy , Random Allocation , Rats, Sprague-DawleyABSTRACT
OBJECTIVE:To study the effects of Carthamus tinctorius on oxidative stress of kidney in rats with type 2 diabetes mellitus. METHODS:Type 2 diabetes mellitus rat model was developed successfully by unilateral nephrectomy and giving high lipid and high glucose diet and low dose streptozotocin (STZ). Then the model rats were randomly divided into four groups:control group,model group,low-dose and high-dose Carthamus tinctorius groups. After treatment for 12 weeks,biochemical indicators,urinary albumin excretion rate (UAER),the activities of superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) and the content of malonaldehyde (MDA) in the renal tissue,and the mRNA gene expressions of both P22phox and P47phox in renal cortex were measured. RESULTS:Compare with model group,Carthamus tinctorius-treated groups (high-dose and low-dose) showed no significant difference in blood glucose level,but much significant decrease in levels of serum creatinine,urea nitrogen and UARE,significant increase in SOD and GSH-PX activities,much significant decrease in MDA content and significant downregulation of mRNA expressions of both P22phox and P47phox. CONCLUSION:Carthamus tinctorius-treatment can mitigate the oxidative stress of renal cortex to play protective effect on kidney and delay the development of diabetic nephropathy.