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Objective To study the protective effect of Rhein on the kidney of type 2 diabetic rats induced by high fat diet.Methods A rat model of type 2 diabetes was induced by high fat diet combined with low dose streptozotocin 35 mg/kg.The diabetic rats were randomly divided into diabetes group, Low, middle and high rhein dose groups (50,100,150 mg/kg), metformin group (300 mg/kg) and normal control group.Blood glucose and urine micro albumin were measured at 0, 2, 4 and 8 weeks respectively.Serum creatinine, urea nitrogen, total cholesterol and triglyceride were measured at 8 weeks.HE staining was used to observe the pathological changes of renal tissue.Effects of rhein on the expression of transforming growth factor-β1 and Smad3 protein in renal tissue of diabetic rats were detected with Western Blot.Results The blood glucose and urine micro albumin in model group were significantly higher than those in normal control group.Each rhein dose group exhibited reduced blood glucose and urinary micro albumin in diabetic rats.The high rhein dose group showed significant reduction of blood glucose and urine micro albumin in diabetic rats (P<0.05).Compared with model group, rhein reduced the serum Cr, BUN, TC and TG values in each dose group, most significantly in the high rhein dose group (P<0.05).The obvious pathological changes of renal tissue in model group were observed with most improved changes in the high rhein dose group.The expression of TGF-β1 and Smad3 protein in renal tissue of diabetic rats decreased significantly (P<0.05).Conclusion Rhein has preventive effect on diabetic nephropathy.The mechanism may relate to the improvement of renal function, regulation of blood lipid and down regulation of TGF-β1 and Smad3 protein expression in renal tissue.
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Objective:To explore the clinical value of vestibular autorotation test (VAT) in the treatment for otogenic vertigo patients. Method:One hundred and twenty-nine definite otogenic vertigo patients were included. All patients underwent the VAT and caloric test (CT). The results were analyzed statistically. Result:In VAT examination, 89 (69.0%) cases were abnormal. In CT examination, 56 (43.4%) cases were abnormal. In the contrast test of VAT and CT, VAT results were abnormal in 47 (36.4%) patients and CT results were abnormal in 14 (10.9%) patients. The number of patients whose both VAT and CT results were abnormal was 42 (32.6%). The total number of patients with various abnormal results was 103 (79.8%). According to statistical analysis, the abnormal result rate of VAT was higher than that of CT. The abnormal result rate of both VAT and CT was higher than that of each single test. There was statistic significance in the difference (χ²=1.670, P<0.05). Conclusion:For otogenic vertigo patients, their abnormal result rate of VAT is higher than that of CT. VAT and CT can be mutually complementary. The combination of VAT and CT can help to understand the function of semicircular canal in the general and provide reference for the treatment of otogenic vertigo diseases.
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Objective:To investigate frequency and position characteristics of the vestibular dysfunction in vestublar neuritis patients. Method:Colaric test (CT), head impulse test (HIT), cervical vestibular evoked myogenic potential (cVEMP) and ocular vestibular evoked myogenic potential (oVEMP) were applied in 43 vestublar neuritis patients to assess their vestublar dysfunction. Superior vestublar nerve (S-VN), inferior vestibular nerve (I-VN), total vestibular nerve (T-VN) and each vestibular end organ incidence rate were calculated and statistically analyzed. Result:CT incidence rate (93.0%) was statistically higher than that of HIT (72.1%) (P<0.01). Total frequency incidence rate (72.1%) was statistically higher than that of low frequency (20.9%) (P<0.01). No high frequency only case was observed. The incidence rate of S-VN only, I-VN only and T-VN was 44.2%, 4.7% and 51.2% respectively. Among them, the incidence rate of I-VN was significantly lower than the others (P<0.01). The incidence rate of vestibular end organs was 17.4% (S-SCC), 44.2% (H-SCC), 20.9% (P-SCC), 39.5% (utricule) and 26.7% (saccule) respectively. The incidence rate of H-SCC was remarkably higher than the other semicircular canals (P<0.01). The difference between utricule and saccule was not statistically significant. Conclusion:The semicricular canal dysfunction in vestibular neuritis patients mainly involves total frequency of vestibular function, low frequency is more common than high frequency. Total vestibular nerve and single S-VN are mostly involved in vestibular neuritis.
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Aim To observe the effects of benazepril and irbesartan on myocardial collagen in chronic heart failure ( CHF ) rats and the possible mechanisms. Methods CHF model in rats was made by partially banding abdominal aorta to induce pressure overload cardiac hypertrophy. The rats were given benazepril or/and irbesartan for 8 weeks. Systolic blood pressure ( SBP) was monitored by rat tail artery. The ultrastruc-ture of myocardium was detected by transmission elec-tron microscope. The content of myocardial hydroxyproline and amount of cross-linked collagen were measured by hydrolysis method. The expression of type Ⅰ and Ⅲ collagen protein in myocardium was investigated by immunohistochemistry. The expression of p-38 MAPK and p-p38 MAPK proteins was detected by Western blot. Results Compared with the model of CHF, there was no significant difference in SBP af-ter treatment. The content of hydroxyproline in myocar-dium, degree of cross-linked collagen, as well as ex-pression of type I collagen, type Ⅲ collagen and p-p38 MAPK proteins were significantly decreased after treatment with benazepril or irbesartan ( P <0. 05 ) , and the combined treatment of them had better effects. Conclusion There is a synergistic effect of attenua-ting the quantity and quality of myocardial collagen in CHF rats by combined use of benazepril and irbesar-tan, which may be related to the down regulation of p-p38MAPK protein expression.
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Objective:To evaluate the effects of platform switching and platform matching system on the marginal bone resorption a-round implant.Methods:Randomized controlled trials (RCTs)that compared marginal bone loss around platform-switched implants with platform matched prostheses were selected from PubMed,EMbase,CBM,CNKI and other electronic databases supplemented by hand search and retrospective collection of literature published or unpublished between 1 991 -201 4.The literature based on inclusion and exclusion criteria was screened by 2 revieweres independently,the quality of the included studies was evaluated,the data were extracted using RevMan 5.2 software for Meta-analysis.Results:1 4 studies with 1 331 implants were included.Meta-analysis showed that peri-implant bone resorption in the platform switching group was significantly less than that in the platform matching group[MD =-0.51 ,95% CI:(-0.72 -0.30),P 0.45 mm (unilateral)was more favorable to implant marginal bone preservation.Conclusion:The present data suggest that platform-switched technology is more conducive to implant bone preservation than platform-matched method.
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<p><b>OBJECTIVE</b>To investigate the effect of TiO₂nanotube arrays covalently modified by recombinant human bone morphogenetic protein- 2(rhBMP- 2) on the early bioactivity of mesenchymal stem cells (MSC) in vitro and to provide experimental evidence for the biochemical modification of titanium implants.</p><p><b>METHODS</b>In the experiment group, double titanium nanotube arrays were prepared by anodization, and were chemically grafted with rhBMP- 2. Mechanically polished pure titanium was used as blank control group, and titanium dioxide nanotubes was used as negative control A group, and titanium dioxide nanotubes + carbonyldiimidazole as negative control B group. Field emission scanning electron microscope (FE- SEM) and X- ray photoelectron spectroscopy (XPS) were used to detect the morphology and physicochemical properties of the experiment group, blank control group and the negative control group. Cell adhesion on the specimen surface of the experiment group, blank control group and negative control group on the 1st day was tested. Cell proliferation on the 1st, 3rd and 5th day and alkaline phosphatase activity on the 5th, 7th and 11th day was also tested.</p><p><b>RESULTS</b>FE- SEM showed that the surface of titanium nanotubes loaded with rhBMP- 2 possessed visible miliary particulate matter. XPS showed that nitrogen peak in the group of titanium nanotubes loaded with rhBMP-2 was significantly greater that those in the other groups. FE- SEM showed that the cells on the surface of the experimental group on the 1st day spread well, better than those in the control group and negative control group. Cell proliferation activity on the 1st day in different groups was not obvious (P>0.05), the A value of the experimental group on the 3rd and 5th day (3.295 ± 0.153, 3.823 ± 0.059) were significantly higher than those in the control group (2.479 ± 0.064, 3.131 ± 0.096) and negative control A group (2.715 ± 0.075, 3.371 ± 0.047) and negative control B group (2.756 ± 0.132, 3.637 ± 0.047) (P<0.05). Alkaline phosphatase activity on the 5th, 7th and 11th day in the experimental group (0.0477 ± 0.0287, 0.0615 ± 0.0016, 0.0667 ± 0.0018) were better than those in the control group, negative control A group and negative control B group (P<0.05).</p><p><b>CONCLUSIONS</b>Titanium nanotube arrays can be loaded with rhBMP-2 by biochemical methods and have good biocompatibility.</p>
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Humans , Alkaline Phosphatase , Metabolism , Bone Morphogenetic Protein 2 , Pharmacology , Cell Adhesion , Cell Proliferation , Materials Testing , Mesenchymal Stem Cells , Microscopy, Electron, Scanning , Nanotubes , Chemistry , Photoelectron Spectroscopy , Recombinant Proteins , Pharmacology , Surface Properties , Titanium , Chemistry , Transforming Growth Factor beta , PharmacologyABSTRACT
Objective:To evaluate the effect of different polishing instruments on the microstructure of composite resin.Methods:Specimens of 5 kinds of resins were randomly divided into three groups and were polished with Astropol(group A),Sof-Lex(group B) and Super-snap(group C)respectively(n=3 for each resin).Specimens of natural enamel surface were used as the controls(group D).The surface roughness(Ra)and microstructure of the specimens were evaluated by an atomic force microscope(AFM).Results:Ra value in group A was lower than that in group B(P=0.015);Z350 XT resin obtained the lowest Ra value among the 5 kinds of resin specimens(P0.05).Conclusion:Astropol polishing instrument is better than Sof-Lex;Z350 XT has better polish performance.The three polishing instruments are ef-fective in polishing the 5 composite resins.
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<p><b>OBJECTIVE</b>To investigate the effects of Ganoderma lucidum polysaccharides (GLPs) on advanced glycation end products (AGEs) and the receptor (RAGE) of aorta pectoralis in the T2DM rats, and explore the protective mechanism of GLPs on the aorta pectoralis.</p><p><b>METHOD</b>SD rats were fed with high-fat diet for 4 weeks and then were injected STZ (30 mg x kg(-1)) to induce the type 2 diabetic rats. Once the T2DM models were set successfully, rats were randomly divided into normal control group, diabetes model (DM) group, berberine (30 mg x kg(-1)) group, GLPs of low (GLPs-L), middle (GLPs-M) and high-dose (GLPs-H) group (GLPs were orally given 200, 400, 800 mg x kg(-1)). After 12 weeks' treatment, the content of fasting blood glucose and AGEs in serum were detected. The expressions of AGEs and RAGE in aortas pectoralis were measured both by immunohistochemistric assays and western-blot analysis.</p><p><b>RESULT</b>Compared with DM group, the content of blood glucose and AGEs in serum were significantly decreased in GLPs-H group and GLPs-M group (P < 0.01). Compared with DM group, the expressions of AGEs and RAGE in aorta pectoralis were decreased in other groups, especially in GLPs-H group (P < 0. 01).</p><p><b>CONCLUSION</b>GLPs could low blood glucose and protect aortas effectively. The mechanisms may be involved in down-regulation the expressions of AGEs and RAGE in aortal tissue.</p>
Subject(s)
Animals , Female , Male , Rats , Aorta , Metabolism , Pathology , Blood Glucose , Diabetes Mellitus, Type 2 , Metabolism , Pathology , Glycation End Products, Advanced , Metabolism , Plant Extracts , Pharmacology , Polysaccharides , Pharmacology , Random Allocation , Rats, Sprague-Dawley , Receptor for Advanced Glycation End Products , Receptors, Immunologic , Metabolism , Reishi , ChemistryABSTRACT
Objective To investigate the effect of hexosamine biosynthesis pathway on the development of insulin resistance induced by high fat diet.Methods Normal male SD rats were randomly divided into three groups:control(fed with normal chow),high fat(fed with high fat diet for 13 weeks),and rosiglitazone (intragastric administration with rosiglitazone for 5 weeks)groups.After 13 weeks,all the rats were sacrificed,serum and muscle triglycerides(TG),serum total cholesterol(TC),and serum and muscle free fatty acids(FFA) were measured.Insulin sensitivity wss evaluated by insulin sensitivity index(ISI)and glucose infused rat(GIR) with the hyperinsulinemic englycemic clamp technique.The flux of HBP in skeletal muscle was detected with the expression level of glutamine-fructose-6-phosphate transaminase(GFAT)mRNA(RT-PCR),the content of UDPGlcNAc(HPLC)and the level of O-GlcNAc glycosylation in skeletal muscle proteins(Western blot). Results Compared with control group,senlm TG,TC,FFA and muscle TG,FFA levels of high fat group increased(aII P<0.01).both ISI and GIR decreased(both P<0.01),and the leveIs of GFAT mRNA(0.51±0.05 vs 0.18±0.02),UDP-GlcNAc[(6.18±0.86 vs 2.42±0.36)nmol/g],and O-GIcNAc glycosylation of skeletal muscle proteins in high fat group were raised(all P<0.01).In rosiglitazone group,serum and muscle TG.FFA welc deceased(all P<0.01).insulin sensitivity was increased(P<0.05)and the flux of HBP[GFAT mRNA 0.27±0.03,UDP-GIcNAc(2.62±0.32)nmol/g]was reduced(all P<0.05)as compared with high fat group. Conclusions High fat diet-induced insulin resistance in rats is correlated with the increased flux of HBP in skeletaI muscle.which is decreased by rosiglitazone.
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<p><b>OBJECTIVE</b>To investigate the effect of Ganoderma lucidum polysaccharides (GLPs) on hemodynamic and antioxidation in the T2DM rats.</p><p><b>METHOD</b>SD rats were fed high-fat diet for 4 weeks and then were injected STZ (30 mg x kg(-1)) to induce the type 2 diabetes mellitus (T2DM). Once the T2DM models were set successfully, rats were randomized into six groups: normal group (NG), group of diabetes mellitus (DMG), groups of low dosage (GLPs-LG), middle dosage (GLPs-MG), high dosage (GLPs-HG) and berberine (BerG). They received GLPs with different dosages (200, 400, 800 mg x kg(-1)) and berberine (30 mg x kg(-1)) continually for 16 weeks. At 16th weekend, the following indices of rats were measured respectively: blood glucose, hemodynamic including LVSP, LVEDP, dp/dt(max) and -dp/dt(max) and the contents of NO, SOD, MDA, GSH-Px, CAT in cardiac tissue. Besides, myocardial ultrastructure was observed by electron microscope.</p><p><b>RESULT</b>Both the middle dosage and the high dosage of GLPs could low blood glucose effectively, and they could reduce LVEP but increase -dp/dt(max). Meanwhile, they could activate GSH-Px, CAT, SOD, NO, but reduce MDA in cardiac tissue and improve the myocardial ultrastructure. Compared to the DM group, the middle dosage, high dosage of GLPs and berberine showed significant improvement. Compared to the berberine group, the middle dosage showed the same effect, but the high dosage was more effective than berberine.</p><p><b>CONCLUSION</b>There is a confirmed action of GLPs in improving the hemodynamic and antioxidation in cardiac tissue of T2DM rats.</p>
Subject(s)
Animals , Female , Male , Rats , Antioxidants , Metabolism , Catalase , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Glutathione , Metabolism , Hemodynamics , Hypoglycemic Agents , Chemistry , Therapeutic Uses , Malondialdehyde , Metabolism , Microscopy, Electron, Transmission , Myocardium , Metabolism , Nitric Oxide , Metabolism , Polysaccharides , Therapeutic Uses , Rats, Sprague-Dawley , Reishi , Chemistry , Superoxide Dismutase , MetabolismABSTRACT
AIM: To investigate the alteration of the vascular response to contracting material and the endothelium dependent vascular relaxation (EDVR) at different stages of type Ⅱ diabetes rats. METHODS: Type Ⅱ diabetes rat model was established by high-energy diet and lower dose of STZ. At 12th and 20th weekends after injecting STZ, the vascular reactivities to phenylephrine (PHE) and KCl and the EDVR induced by Ach were measured respectively in the isolated aorta rings. RESULTS: At 12th weekend after injecting STZ, the response to PHE increased, the reactivity to KCl kept unchanged, and the EDVR was damaged lightly. But at the 20 th weekend after injecting STZ, the response to PHE increased further and the reactivity to KCl markedly reinforced, and the EDVR was obviously damaged. CONCLUSION: The response of great vessels to contracting material increased, but the EDVR attenuated at different stages of type Ⅱ diabetes rats. These changes are further reinforced along with the developing of disease duration.
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AIM: To study the expression of type Ⅰtransforming growth factor ?(T?R-Ⅰ)in renal cortex in streptozotocin-induced type Ⅱ diabetic mellitus and the regulation of valsartan. METHODS: The rat models of type Ⅱ diabetic rats were made. At the end of the 20th weeks,the kidneys were taken out to measure the expression of T?R-ⅠmRNA by RT-PCR. RESULTS: The expression of T?R-ⅠmRNA in diabetic rats without any therapy ( 0.72? 0.14) was higher than that in control ( 0.26? 0.12) (P
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Aim To investigate the myocardial hypertrophy,the expression of transforming growth factor ?1(TGF-?1),Smad3 and Smad7 proteins in spontaneous hypertensive rats(SHR)and the effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril and candesartan for 12 weeks.The tail arterial pressure was measured every two weeks.At 12 th weekend,cardiac configuration,heart mass index,area of cadiocytes,concertrations of AngⅡin plasma and myocardium,expressions of TGF-?1、Smad3 and Smad7 proteins were measured respectively.Results The arterial pressure,wall thickness,heart mass index,area of cardiocytes and the expressions of TGF-?1,Smad3 proteins increased in SHRs but were attenuated after the treatment of benazepril or candesartan.After the combined treatment,the synergistic effect could be observed.The levels of cardiac tissue and plasma AngⅡwere reduced.The expressions of Smad 7 were up-regulated after the treatment of benazepril or candesartan,while they were stable after the combined use.Conclusion There is a synergistic effect of attenuating myocardial hypertrophy in SHRs by combined use of benazepril and candesartan.It may be related to the regulation of Ang Ⅱ,decreasing the expressions of TGF-?1 and Smad3.
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Aim To investigate the effects of anisodamine on the pressure of portal vein of experimental liver fibrosis and its mechanisms of action. Methods The experimental liver fibrosis model was produced by CCl_4. The preventive group was treated ten weeks with anisodamine 7.0 mg?kg~(-1) ip once everyday. All therapeutic groups were treated six weeks with anisodamine 7.0 mg?kg~(-1) or 14.0mg?kg~(-1) ip once everyday. After CCl_4 injection for ten weeks, the pressure of portal vein,the content of NO in livers, and liver iNOS and eNOS mRNA expressions were detected with different methods.Results The pressure of portal vein was significantly reduced in anisodamine preventive group and anisodamine therapeutic groups. The liver content of NO and the expression of iNOS and eNOS were all inhibited by the treatment of anisodamine.Conclusion Anisodamine reduced the expressions of iNOS and eNOS to synthesis of NO in liver. As a result, the pressure of portal vein of fibrosis rats decreased. So Portal hypertension of liver fibrosis may be improved by anisodamine in patients.
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Aim To investigate effects of moxonidine on hemodynamics in anesthetized rats. Methods The indexes of hemodynamics were examined by catheterization of arteries in anesthetized Wistar rats. Results DBP, +dp/dt_ max, -dp/dt_ max,t-dp/dt_ max ,V_ pm and V_ max were significantly declined in dose-dependent manner after administration, but HR and SBP didn't change significantly. Conclusion These results showed that antihypertensive effects of moxonidine were related to inhibition of systolic and diastolic functions of myocardium.Furthermore,the antihypertensive effects of moxonidine were associated with reduction of peripheral vascular resistance.
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Aim To investigate the alteration of the nitric oxide (NO), the expression of nitric oxide synthase (NOS) mRNA at different stages of the cardiomyopathy in type 2 diabetes rats, and the protective effects of valsartan. Methods Type 2 diabetes model was established by high-energy diet, lower dose of STZ treated SD rat. The treatment period of valsartan was 8 weeks. At 12th and 20th weekend after injection of STZ, cardiac function, heart weight index, concentrations of NO in myocardium and plasma, expressions of iNOSmRNA and eNOSmRNA were measured respectively.Results From 12th week to 20th weekend, the left ventricular systolic and diastolic function was decreased and the heart weight index was increased in diabetes control group (DC group) compared with normal control group (NC group). The levels of the cardic tissue and plasma NO were higher at 12th weekend and lower at 20th weekend in DC group than that in NC group. The expression of iNOSmRNA in cardiac tissue was obviously up-regulated at 12th or 20th weekend while the expression of eNOSmRNA was down-regulated at 20th weekend in diabetes rats. All these abnormalities were partially attenuated by valsartan. Conclusion The abnormal change of the NO and expression of NOSmRNA might be related to the cardiomyopathy in type 2 diabetes. Valsartan might play a protective role in the myocardial disease.
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Aim To investigate the effects of pumpkin polysaccharide(PP) on Fas、Fas-L、Bcl-2 and Bax expression in the pancreas of diabetic rats.Methods Rats were injected intraperitoneally(ip) with streptozocin(STZ) 60 mg?kg-1 to induce diabetic model.The diabetic rats were given PP 150 mg?kg-1,300 mg?kg-1,600 mg?kg-1.The blood sample were taken after three weeks.Blood glucose was measured by glucose oxidase method;The expression of the Fas and Fas-L have been determined by using immunohistochemistry(S-P method);The expression of Bax mRNA and Bcl-2 mRNA were checked up by Reverse transcription PCR(RT-PCR).Results PP could decrease the level of blood glucose in streptozotocin-induced diabetic rats;After three weeks,The expressions of the Fas and FasL in ? cell of streptozotocin-induced diabetic rats were obviously lower;The expression of Bax mRNA was obviously down-regulated,the expression of Bcl-2 mRNA was obviously up-regulated,and the ratio of Bcl-2/Bax was advanced after the diabetic rats were given PP.Conclusions PP could decrease the level of blood glucose of the diabetic rats.The mechanism was related to decreasing the expressions of the Fas and FasL and regulating the expressions of Bcl-2 and Bax in the pancreas of diabetic rats.
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Aim To investigate the relationship between oxidative stress and the aortic endothelial cells injury in type 2 diabetes rats,as well as the effect of valsartan. Methods The type 2 diabetic models were induced by low dose of streptozotocin (STZ) with high-energy diet.12 weeks after injecting STZ, rats were randomly divided into three groups: normal control, diabetes control and valsartan (24 mg?kg-1?d-1, 8 weeks, ig.) treated diabetes. At the 12th and 20thweek end, such indices as the endothelium-dependent vasodilation and the shape of aorta endothelium, the serum contents of SOD, GSH-Px , MDA and NO, and the level of NOS gene expression in aorta were measured. Results ① At the 12th weekend,in the diabetes group, the relaxation of aortic rings to low concentration of Ach declined, the aortic endothelial cells intumesced, contents of serum SOD, GSH-Px, MDA and NO significantly increased, the expression of iNOS mRNA in aorta obviously up-regulated while the expression of eNOS mRNA showed no change. ② At the 20th weekend,in the diabetes control group, the dilatory reactivity of aortic rings decreased to each concentration of Ach, the aortic endothelium appeared degenerative and necrotic, activities of SOD and GSH-Px decreased as well as the content of NO, the content of MDA increased continuously, and the iNOS mRNA expression up-regulated while eNOSmRNA expression down-regulated. Valsartan could regress the aggravation and improve contents of serum SOD, GSH-Px, MDA, NO and NOS mRNA of the aorta. Conclusion The oxidative stress and abnormality of NO participate the process of aortic endothelial cell injury. Valsartan plays a protective role partially through enhancing antioxidation effect and adjusting NO production.
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The phospholipase A2 ( PLA2 ) is one of the main constituents of the bee venom. Its hypotensive effect and mechanism are studied in this report.In the anaesthetized rats and cats, the PLA2 of the bee venom given intravenously caused a quick and profound fall in the arterial blood pressure.The results of this study indicate that its hypotensive effect is mainly concerned with releasing the endogenous histamine. If the antagonists of H1 and H2 receptor are administered together, its hypotensive action will be countered.
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Aim To investigate the effect of irbesartan and spironolactone on expressions of connective tissue growth factor(CTGF),P-p38MAPK proteins during vascular remodeling in renovascular hypertensive rats(RHR).Methods Renovascular hypertension was induced by two kidney one clip(2K1C)operation.8 weeks later,RHRs were given irbesartan or(and)spironolactone for 8 weeks.After 8 weekstreatment,the morphometric measurements were performed in the mesenteric arterioles.Concertration of carboxyterminal propeptide of typeⅠprocollagen(PⅠCP)and N-terminal propeptide of type Ⅲ procollagen(PⅢNP)in blood serum was measured by enzyme linked immunosorbent assay method,and the media collagen area was assessed by collagne-specific Picro-sirius red staining with computerized video processing.Expressions of collagen type I,CTGF,P-p38MAPK proteins were detected using immunohistochemistry respectively.Results The arterial systolic pressure was attenuated significantly after the treatment of irbesartan,and this effect could not be enhanced by spironolactone.The media thickness over lumen ratio,media cross-sectional area over luminal area ratio of mesenteric arterioles,concertration of PⅠCP and PⅢNP,media collagen area,and expression of collagen typeⅠwere significantly increased in RHRs but ameliorated by irbesartan and spironolactone.Meanwhile,the expressions of CTGF,P-p38MAPK proteins were up-regulated in RHRs but blunted significantly after the treatment of irbesartan and spironolactone.The combined treatment had the synergic effects.Conclusions There is a synergistic effect of attenuating extracellular matrix(ECM)producing and amelioration of vascular remodeling(VR)by combined use of irbesartan and spironolactone.It maybe related to the expressions of CTGF and P-p38MAPK proteins down regulated by these two drugs.