Protective effects of pioglitazone on endothelial function in rats with hypercholesterolemia

AIM: To investigate the effects of pioglitazone,a PPARγ agonist,on endothelial cell (EC) dysfunction in hypercholesterolemic rats.METHODS: 36 healthy male Wistar rats were assigned to one of the following groups randomly (six rats in each group): control,hypercholesterolemia (HC),and HC treated with pioglitazone 1.5 mg·kg^-1·d^-1,3 mg·kg^-1·d^-1,10 mg·kg^-1·d^-1 and 20 mg·kg^-1·d^-1 (HC＋PIO),respectively.EC function was determined by comparing vasorelaxation to ACh,an EC dependent vasodilator,and acidified NaNO₂,an EC-independent vasodilator.Maximal positive and negative values of the instantaneous first derivative of LVP (+dp/dt_max and dp/dt_max) were determined by MS2000 system.RESULTS: (1) Hypercholesterolemia caused a significant endothelial diastolic dysfunction (maximal relaxation to ACh: 50.51%±2.45% vs 99.78%±3.01% in control,P<0.01).(2) Treatment with pioglitazone relieved EC-dependent vasodilatation in a dose dependent manner,and 10 mg·kg^-1·d^-1 is the best dose.(3) Pioglitazone not only improved EC function,but also reduced cardiac functional injury induced by hypercholesterolemia.CONCLUSION: EC dysfunction induced by hypercholesterolemia can be directly extenuated by pioglitazone,which may effectively prevent from subsequent atherosclerosis and ischemic heart disease.     

Protective effects of tongxinluo,carvedilol and valsartan on microvascular endothelial function and integrity after late reperfused AMI in rabbits

AIM:To compare the protective effects of tongxinluo, a Chinese medicine, and carvedilol and valsartan on myocardium microvascular endothelial function and integrity after late reperfusion of acute myocardial infarction (AMI) in rabbits. METHODS:Forty-eight rabbits were randomly assigned to the following groups:(1) sham operated rabbits;(2) ischemia-reperfusion (I-R) controls;(3) tongxinluo (1.0 g·kg^-1·d^-1);(4) carvedilol (5 mg·kg^-1·d^-1);(5) valsartan (10 mg·kg^-1·d^-1) and (6) ticlopidine + aspirine (30 and 20 mg·kg^-1·d^-1, respectively) groups. After 3 d of drug treatment, the left coronary artery in the rabbit was ligated for 2 h and loosed subsequently for another 2 h. The serum levels of nitric oxide (NO₂^-/NO₃^-) and endothelin (ET) at baseline before AMI, 2 h after both AMI and reperfusion were examined. Also, the number of circulating endothelial cells (CEC), MI size and percentage myocardium focal bleeding incidence were determined 2 h after reperfusion. RESULTS:(1) The baseline level of NO₂^-/NO₃^- was significantly higher in tongxinluo group than that in other groups (all P<0.01), whereas the content of ET was not significantly different among the groups. 2 h after both AMI and reperfusion, NO₂^-/NO₃^- was significantly reduced (P<0.05, P<0.01) and ET was significantly increased in each group as compared with their baseline (P<0.05, P<0.01). Yet among the groups, NO₂^-/NO₃^- was still significantly higher and ET was significantly lower in tongxinluo-treated group than that in the other groups (P<0.05, P<0.01). (2) CEC number was significantly increased in I-R controls as compared with sham group (P<0.01), and was significantly reduced in the tongxinluo-treated groups as compared with I-R controls (P<0.05). (3) MI size was significantly reduced in the four treatment groups as compared with I-R controls (all P<0.01). (4) The percentage of myocardium focal bleeding incidence was significantly lower in tongxinluo and valsartan-treated groups than that in I-R controls (P<0.05, P<0.01). CONCLUSION:Tongxinluo as well as valsartan effectively protectsmyocardium endothelial function and integrity during AMI and late reperfusion,with the effects of tongxinluo being superior.     

Effects of different doses of L-dopa on rotational behavior and amounts of cells expressing D2 receptors in hemiparkinsonian rats

AIM：To observe the effects of different doses of L-dopa on the rotational behavior and amounts of cells expressing D₂ receptors in striatum in hemiparkinsonian rats.METHODS：A hemiparkinsonian model was established in rats by pretreatment with 6-hydroxydopamine.The D₂ receptor expression were detected by immunohistochemical staining.The numbers of rotations induced by apomorphine was counted within 30 min before and after L-dopa (10 mg·kg^-1·d^-1,50 mg·kg^-1·d-^-1 or 100 mg·kg^-1·d^-1,ip) was introduced to Parkinson’s disease (PD) model rats for 15 days.RESULTS：In successful PD model rats,the increased percentage of D₂ receptor in lesioned side compared with intact side was associated linearly with the numbers of rotations within 30 min (r=0.927,P<0.01).After high dose of L-dopa intervention to PD model,the numbers of rotations decreased significantly (P<0.05),the amounts of cells expressing D₂ receptor at the lesioned side striatum decreased significantly (P<0.01).CONCLUSION：After high dose of L-dopa intervention,rotation behavior of PD rats improves,and D₂ receptor is down-regulated significantly.     

The experimental study on mouse pristine hepatic fibrosis induced by different doses of alcohol

AIM: To explore the difference on formation mechanism and the pathology in the process of early liver fibration induced by two dose of ethanol. METHODS: 24 male KM mice were randomly divided into 3 groups which are control group, low dose of alcohol group and high dose of alcohol group, respectively. The mice treated with 8 g·kg^-1·d^-1 ethanol, 3 g·kg^-1·d^-1 ethanol by oral were killed 30 days later. The liver histomorphology,inflammation grade and fibration staging were observed and the areas of collagen per high power field were calculated by hematoxylin-feosin (HE) and Masson staining; the expression of Toll like receptor-4(TLR-4), α-smooth muscle actin (α-SMA) and content of transforming growth factor-β (TGF-β), nuclear factor-kappa B (NF-кB) protein, BMP and activin membrane-bound inhibitor (Bambi) mRNA were measured using immunohistochemistry, Western blotting, real-time quantitative polymerase chain reaction, respectively; apoptosis cell number was calculated by In Situ Nick-End Labeling (TUNEL). RESULTS: Different degree of fibration mice induced by ethanol appeared (P<0.01) and hepatic stellate cells (HSCs) in these mice liver were activated, meanwhile the apoptosis cell number increased too (P<0.01). The liver fibration at high dose group was more serious than that at low dose group mice, and the number of apoptosis cells showed the same trend as fibration, but the content of Bambi mRNA in high dose group down regulated compared to that in low dose group (P<0.05). On the other hand, the expression of TLR-4 enhanced in low dose group while decreased in high dose group compared to control group (P<0.01). CONCLUSION: The mechanism of early mouse liver fibration induced by two dose of alcohol is different. Apoptosis may be more responsible for the liver fibration induced by high dose alcohol than TLR-4 pass way, and there is a TLR-4 independent pathway to down-regulate the Bambi that probably is one of the reasons that the fibrosis is more serious in the high dose group.     

Influences of Vit-E on the mtDNA damage and Ca2+ homostasis of hippocampus and antioxidative ability in brain of aging mice induced by D-galactose

AIM: To study the influences of vitamin E (Vit-E) on the mtDNA damage and Ca²⁺ homeostasis in hippocampus and antioxidative ability in aging brain induced by D-galactose.METHODS: D-galactose (1 000 mg·k^-1·d^-1 ) was injected into mice hypodermically for 8 weeks to induce aging animal model, and Vit-E (100 mg·kg^-1; 250 mg·kg^-1) was administered for 6 weeks by ig at the 3rd week of making model. After Vit-E treatment for 8 weeks, water maze test was used to determine the ability of mice’s learning and memory. The activities of glutathione peroxidase (GSH-Px) and succinate dehydrogenase (SDH), the content of nitric oxide (NO) and activity of nitric oxide synthase (NOS) in the brain tissue were detected separately. Fura-2/AM, double-wave-length fluorospectrophotometer and PCR method were used to measure the concentration of calcium ion and mtDNA mutation in the hippocampus cells.RESULTS: Administration of Vit-E improved significantly the ability of learning and memory in model mice, inhibited the activity of NOS and decreased the amount of NO, and increased the activities of GSH-Px and SDH respectively in brain tissues, decreased the concentration of calcium ion (P<0.01, P<0.05), and prevented the damage of mtDNA in hippocampus.CONCLUSION: Vit-E can enhance the antioxidative ability, regulate the homeostasis of Ca²⁺ and inhibit the damage of mtDNA caused by oxidative stress in aging brain, and improve the ability of learning and memory in aging mice.     

Effects of atorvastatin on the experimental autoimmune myocarditis in Lewis rats

AIM:To test the hypothesis that atorvastatin affects T cell-mediated autoimmunity through modulating the balance of Th1/Th2 and reduces the severity of EAM. METHODS:Myocarditis was induced in Lewis rats by injection of porcine cardiac myosin. High-dose (10 mg·kg^-1·d^-1) or low-dose (1 mg·kg^-1·d^-1) atorvastatin or vehicle was administered orally for 3 weeks. On day 21, echocardiography was examined and the severity of myocarditis was detected by histopathological evaluation. Levels of serum IFN-γ, IL-2, IL-4 and IL-10 were measured by ELISA. RESULTS:Cardiac function and histological severity of myocarditis were improved in the two atorvastatin-treated groups. Treatment with atorvastatin decreased the levels of Th1 cytokine (IFN-γ, IL-2) and increased the levels of Th2 cytokine (IL-4, IL-10). CONCLUSION:These results suggest that HMG-CoA reductase blockade may be a promising new strategy for the treatment of autoimmune myocarditis.     

Rifampicin protects rats against rotenone-induced dopaminergic neurons damage

AIM:To investigate the protective effect of rifampicin on rotenone-induced apoptosis of dopaminergic neurons and expression of α-synuclein in rats. METHODS:Highly selective lesions and high expression of α-synuclein in nigrostriatal dopaminergic neurons in rats were induced by chronic subcutaneous exposure to rotenone at dose of 1.5 mg·kg^-1·d^-1 for 3 weeks. At the same time, rifampicin was administered at dose of 30 mg·kg^-1·d^-1 by intragastric administration for 3 weeks. The changes of behavior, pathology and immunoreactivity of TH and α-synuclein in SNc were observed. RESULTS:Obvious changes of behavior, pathology and TH immunoreactivity in SNc were observed in male SD rats injected subcutaneously with rotenone and rifampicin protected rats against these toxic effects induced by rotenone. CONCLUSION:Rifampicin has extensive protective effects against rotenone-induced neurotoxicity, which is related to inhibiting the expression and aggregation of α-synuclein.     

Effect of atorvastatin on ventricular remodeling in spontaneous hypertension rats

AIM：To explore the effect of atorvastatin on cardiac remodeling in spontaneous hypertension rats (SHR).METHODS：Twelve spontaneous hypertension rats were divided randomly into two groups：group of atorvastatin (atorvastatin 50 mg·kg^-1·d^-1) and group of SHR (0.5% mucilage of arabic gum,10 mL·kg^-1·d^-1).Additionally,six male Wistar-Kyoto rats (0.5% mucilage of arabic gum,10 mL·kg^-1·d^-1) were selected as control group.Systolic blood pressure was assessed with the tail-cuff method.After six weeks,entire heart,and left ventricle were weighed.The left ventricular weight index was calculated and myocardial hydroxyproline and collagen protein concentration were measured.The serum high sensitivity CRP (hs-CRP) was measured by nephelometry.The localization of vascular cell adhesion molecule (VCAM) in myocardium was investigated by immunohistochemistry assays.The level of NF-κB mRNA expression was detected with in situ hybridization.Ultrastructure in cardiac muscle was also observed under transmission electron microscope.RESULTS：The expression of myocardial VCAM and NF-κB in SHR group was stronger than that in WHY group.Compared with SHR group,entire heart weight,left ventricular weight,left ventricular weight index,serum hs-CRP,myocardial hydroxyproline and collagen protein concentration was decreased,the expression of myocardial VCAM and NF-κB in SHR group was weaker than that in atorvastatin treatment group.The myocardial pathological change such as incomplete karyotheca in cardiac muscle cells,no clear of transverse striation and the mess in myofibril alignment,and hyperplasy in interstitial collagen fibre were observed in SHR group and these changes were improved in atorvastatin treatment group.CONCLUSION：The cardiac remodeling in SHR is improved by atorvastatin.The molecular mechanism may be related to its down-regulating the expression of VCAM protein and NF-κB and inhibiting myocardial chronic inflammation.     

Protective effect on hepatic insulin resistance of Astragalus polysaccharide in the high fat-fed mice model

AIM: To investigate the effect and mechanism of Astragalus polysaccharide (APS) on the amelioration of hepatic insulin resistance in high fat-fed mouse model.METHODS: C57BL/6J mice (n=26) were divided into three groups randomly: C group (an animal model for control,n=10);IR group ( an animal model of insulin resistance,n=8) and IA group (an animal model in high-fat diet with APS treatment for12 weeks,700mg·kg^-1·d^-1,ig).High-fat diet was used to induce the formation of insulin resistant.The parameters and insulin sensitivity of the animals were observed.The pathological features of the liver were presented through microscope and TEM.The expression changes of hepatic GSK3β were measured by Western blotting.RESULTS: In this study,the fat-fed mouse model of insulin resistance was established successfully.The mice in IA group responded to the 12-week APS therapy with a significant decrease in the level of blood glucose,plasma insulin,body weight,hepatic TG/FFA and improved glucose tolerance compared with those in IR group.In addition,the expression and the activity of GSK3β were lower in IA group (vs IR group，P<0.05).We also found the hepatic steatosis could be significantly alleviated with APS therapy.CONCLUSION: These results indicate that APS prevents the occurrence of insulin resistance and the hepatic steatosis induced by high-fat diet,at least in part by inhibiting the expression and activity of the hepatic GSK3β.     

Effects of thalidomide on the expression of NF-κB and TNF-α in experimental hepatic fibrotic rats

AIM: To study the effects of thalidomide on the expressions of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α) in rat liver fibrosis.METHODS: The fibrosis of rat liver was induced by intraperitoneal injection of carbon tetrachloride thrice weekly.Meanwhile thalidomide (10 mg·kg^-1·d^-1 or 100 mg·kg^-1·d^-1) was given daily by the intragastric route for 8 weeks.Serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),prealbumin (PA),hyaluronic acid (HA) and laminin (LN),and hydroxyproline (HYP) contents in the liver,NF-κB p65 and α-smooth muscle actin (α-SMA) protein in the liver,IκBα and TNF-α protein in cytoplasm and NF-κB p65 protein in nucleus and TNF-α mRNA levels in the liver were studied.RESULTS: Compared with the model group,the Knodell score,serum ALT,AST,HA,LN levels and HYP contents in liver,NF-κB p65 protein in nucleus and α-SMA protein in the liver,and TNF-α mRNA and protein in the liver of rats given high dose of thalidomide were decreased significantly (P<0.01).Meanwhile PA level and IκBα protein in cytoplasm were elevated significantly (P<0.01).CONCLUSION: Thalidomide exerts its effect on the down-regulation of NF-κB-induced TNF-α via inhibiting dissociation and degradation of IκB and prevents liver fibrosis in rats.     

Astragali radix extract ameliorates renal resistance to atrial natriuretic peptide in rats with experimental nephrotic syndrome

AIM: To study the effects of astragali radix extract (ARE) on renal resistance to atrial natriuretic peptide (ANP) in rats with experimental nephrotic syndrome. METHODS: Male Sprague-Dawley rats were randomly divided into normal control, adriamycin nephropathy (ADR), ADR treated with ARE (2.5 g· kg^-1· d^-1) and ADR treated with benazepril (10 mg· kg^-1· d^-1). After 6 weeks, rats received intravenous infusion of 2% body weight isotonic saline. Urinary cGMP excretion (U_cGMPV), plasma ANP level, renal PDE5 activity and protein expression were also detected. RESULTS: ARE increased U_NaV while ACEI was not natriuretic. Nephrotic rats had a blunted natriuretic response and reduced rate of U_cGMPV after volume expansion despite higher plasma ANP concentration. ARE increased U_cGMPV and restored partly natriuretic response to volume expansion. The activity and protein abundance of renal PDE5 were high in nephrotic rats. ARE significantly reduced the PDE5 activity and protein expression. CONCLUSION: ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDE5.     

Therapeutic effect of sodium arsenite on rheumatoid arthritis in rats

AIM:To study the molecular mechanism of rheumatoid arthritis (RA) and the effects of sodium arsenite on AP-1 and MIP-1. METHODS:32 Wistar female rats were randomly divided into 4 groups: normal control (C), arthritis (A), low concentration of sodium arsenite (LSA) and high concentration of sodium arsenite group (HSA).The LSA group and the HSA group were treated with sodium arsenite (0.5 mg·kg^-1·d^-1 and 1.0 mg·kg^-1·d^-1) through abdominal cavity injection for 20 days. The normal control group and the model group were treated with saline (0.2 mL/d). The AP-1 and MIP-1α expression of synovium in four groups were determined by immunohistochemistry. Light microscope was used to observe the synovium with HE staining. RESULTS:Compared with C group, the expression of AP-1 and MIP-1α in the synovium up-regulated in A group (P<0.01) and were inhibited by sodium arsenite treatment (P<0.05), especially in HSA group. CONCLUSION:The activated AP-1 and MIP-1α play an important role in the development of rheumatoid arthritis. Sodium arsenite down-regulated the expression of AP-1 and MIP-1α and may have some therapeutic effects in RA.     

Effects of DEHP on testosterone synthesis in fetal Leydig cells of newborn male rats

AIM: To observe the effects of diethylhexylphthalate(DEHP) on testosterone synthesis in fetal Leydig cells(FLC) of newborn male rats.METHODS: The pregnant rats were exposed to DEHP at dose of 10 mg·kg^-1·d^-1, 100 mg·kg^-1·d^-1 or 750 mg·kg^-1·d^-1(body weight) by gavage from gestation 12 days(GD 12) to postnatal 1 day(PND 1) respectively. The serum level of testosterone was detected by chemiluminescence. The morphology of FLC from the testes was observed under light microscope and transmission electron microscope. The mRNA expression of steroidogenic acute regulatory protein(StAR) and insulin-like growth factor I(IGF-I) was detected by real-time PCR(ΔΔCT). RESULTS: The serum testosterone level in low dose group was significantly higher than that in control, middle and high dose groups. The serum testosterone level in middle and high dose groups was significantly lower than that in control group(P<0.05). Light microscopy showed the aggregative cluster distribution of FLCs in low dose group, while manifested as tumor-like hyperplasia of FLCs in middile dose group and high dose group. Under electron microscope, the FLC in low dose group showed oval-shape or long spindle-shape, the lipid particles were decreased, but smooth endoplasmic reticulum and mitochondria were increased in cytoplasm. In middle and high dose group, the FLC were spindle or oval-shaped, showed large or small, nuclear large, round, rich in cytoplasm and cell aggregation, the cytoplasm was rich lipid particles with deep-stained, smooth endoplasmic reticulum and mitochondria were expanded. Compared to control group, the mRNA expression of StAR in low, middle and high dose group was decreased. The mRNA expression of StAR in high dose group was decreased more significantly(P<0.01) as compared to that in control group, while the mRNA expression of IGF-I in low dose group and middle dose group was increased, but that only in low dose group was increased more significantly as compared to control group(P<0.01). CONCLUSION: DEHP has toxic effect on FLC and changes the morphology and steroidogenic capacity in testicular FLC. The low dose of DEHP elevates the gene expression of IGF-I, and IGF-I stimulates the production of testosterone by FLC. The high dose of DEHP may inhibit the gene expression of StAR to reduce the serum levels of testosterone.     

Protective effects of total saponins of panax notoginseng on myocardial hypertrophy and fibrosis induced by isoproterenol in rats

AIM: To investigate the protective effects of total saponins of panax notoginseng (PNS) on myocardial hypertrophy and fibrosis induced by isoproterenol (ISO) in rats.METHODS: Myocardial hypertrophy and fibrosis model of rats were induced by injection of ISO (5 mg·kg^-1·d^-1,sc) for 7 days.From day 2,the rats were administered with PNS at dose of 25 and 50 mg·kg^-1·d^-1,ip for 14 days,the control and ISO model group were received saline injection.Then,the heart-weight (HW),left ventricular weight (LVW),the ratio of HW/BW and LVW/BW (LVI) were measured;the hydroxyproline and malondialdehyde (MDA) and angiotensin (AngII) content of left ventricle.The level of nitric oxide (NO),nitric oxide synthase (NOS),superoxide disrnutase (SOD) and glutathione peroxidase (GSH-Px) activities in left ventricle were determined by spectrophotemetry and radioimmunoassay,respectively.RESULTS: Compared with NS control group,the ratio of HW/BW,LVW/BW and the content of hydroxyproline,AngII,MDA and iNOS activity in the left ventricle were significantly increased.The cNOS,SOD,GSH-Px activities and NO content were obriously decreased in the ISO model group.After treatment with PNS,the left ventricular NO content,cNOS,SOD and GSH-Px activities were markedly higher than those in ISO model group.The content of MDA,AngII and iNOS activities and the ratio of HW/BW,LVI were significantly lower than those in ISO model group.CONCLUSION: PNS reverses the myocardial hypertrophy and fibrosis induced by isoproterenol in rats.This effect may be related to eliminating the oxygen free radicals and raising NO level.     

Effect of pioglitazone on glucose metabolism and PPAR-γ expression in lipid-infused rats

AIM: To investigate the effect of pioglitazone (Pio) on glucose metabolism and peroxisome proliferators-activated receptor (PPAR)-γ expression in free fatty acid (FFA) -induced insulin resistance in rats. METHODS: A hyperinsulinaemic-euglycaemic clamp and ［3-3H］-glucose tracing technique were used in awake rats. Glucose metabolism in vivo and PPAR-γ in adipose tissue expression were assessed with elevation FFA by lipid infusion over 4 h in rats pretreated with or without Pio.RESULTS: During steady-state of clamp, there was a significant increase in plasma FFA in two lipid-infused groups, compared to control rats (P<0.01). The glucose infusion rates (GIR) in Pio-treated rats (P/L group), compared with controls, were significantly reduced ［(20.6±0.4) mg·kg^-1·min^-1 vs (33.6±0.6)mg·kg^-1· min^-1, P<0.01］, whereas the GIR was lower in the lipid group (L group) than that in the P/L group［(12.6±0.8) mg·kg^-1·min^-1 vs (20.6±0.4) mg·kg^-1·min^-1, P<0.01］. The hepatic glucose production (HGP) was significantly suppressed (85%) ［(18.3±2.1)mg· kg^-1·min^-1 (basal) vs (2.7±2.4)mg· kg^-1·min^-1, and (17.5±2.6) mg· kg^-1·min^-1 vs (2.6±1.0)mg· kg^-1·min^-1］, all P<0.01 during clamp in control and P/L groups. The suppressive effect of insulin on HGP was significantly blunted in L group［(17.3±2.1)mg· kg^-1·min^-1 vs (15.8±1.5)mg· kg^-1·min^-1］. The rate of glucose disappearance (GRd) was significantly reduced in two lipid-infused rats compared with controls［(26.6±1.6)mg· kg^-1·min^-1 and (23.2±0.9)mg· kg^-1·min^-1 vs (37.7±2.6)mg·kg^-1·min^-1,P<0.01］. The PPAR-γ expression of adipose tissue in P/L group was significantly upregulated. CONCLUSION: Lipid-infusion induces an acute insulin-resistance in vivo. Pio treatment upregulates the PPAR-γ of adipose tissue and suppresses HGP. Pio can protect partly against lipid-induced insulin resistance.     

Effects of angiotensionⅡon metalloproteinases and matrix in hypertrophied myocardium from infarcted rats

AIM: To investigate the roles of angiotensionⅡ (AngⅡ) receptors (AT₁, AT₂) antagonists on matrix metalloproteinases (MMPs) and extracellular matrix (ECM) system in septal myocardium from infarcted rats.METHODS: The model of rat myocardium infarction (MI) was established by permanent ligation of the left coronary artery. The treatments of the AT₁ receptor antagonist valsartan (10 mg·kg^-1·d^-1) or AT₂ receptor antagonist PD123319 (30 mg·kg^-1·d^-1) were started 7 days prior to surgery. On day 14 after MI, protein levels of MMP-2, 3, 9, fibronectin (FN), tenascin-C (TN-C) in interventricular septum (IS) were determined. The distributions of FN and TN-C were also determined by immunofluorescence.RESULTS: Pathological changes of IS on day 14 after MI showed typical myocardial hypertrophy. Protein expressions of MMP-2, 3, 9 and TN-C of IS in banding group were higher than those in sham-operation group (P<0.01). The expressions of TIMP-1 and FN were lower than those in sham-operation group (P<0.01). Protein expressions of MMP-2, 3, 9 and TN-C in valsartan group were obviously lower than those in banding and PD123319 groups (P<0.01). TIMP-1 and FN protein expressions in valsartan group were higher than those in banding and PD123319 groups (P<0.01). No difference between banding and PD123319 groups was observed (P>0.05).CONCLUSION: AngⅡis involved in myocardium remodeling in infarcted rats, which is mediated via AT₁ receptor to degrade matrix by MMPs. The heart protection of AT₁ receptor antagonists may relate to inhibition of MMPs.     

Effects of local application of simvastatin on osteoporotic fracture healing in rats

AIM: Many studies have documented an anabolic effect of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, on undisturbed bone. Reports of their effects on fractured skeleton were limited. A study was therefore conducted to check the effects of statins on fracture healing. METHODS: Simvastatin (10 mg·kg^-1·d^-1) was injected subcutaneously to tissue overlying the site of fractured tibiae of ovariectomized rats for a treatment period of 5 d. Vehicle reagent was used as control. Healing quality was evaluated at 1, 2 and 4 weeks after fracture. RESULTS: Compared with vehicle group, callus cross section area in simvastatin treated rats were significantly enlarged by 21.3% (P<0.05) at 1 week and by 21.5% (P<0.05) at 2 weeks. New woven bone was relatively substantive and arranged more tightly and regularly at 2 and 4 weeks, and maximal load was increased by 57.5% (P<0.05) at 2 weeks and by 31.4% (P<0.05) at 4 weeks. Histomorphometrically, simvastatin was associated with a significant (P<0.05) increase in mineralization width (MLW), mineralization volume (MLV) and mineral apposition rate (MAR). CONCLUSION: Current study suggests that local application of simvastatin promotes fracture healing in ovariectomized rats.     

Influence of Weimaining on the cell cycle of murine Lewis lung carcinoma

AIM:To investigate the anti-tumor effect of Weimaining (WMN) on a murine Lewis lung carcinoma (3LL) and the influence on the cell cycle. METHODS:The inhibitory rate of WMN in 3LL growth was detected by replicating the model of 3LL. The effect of the drug on 3LL cell cycle and the influence of the drug on the expression of cyclin D1 protein were investigated by flow cytometry and immunohistochemical staining. RESULTS:The results showed that the inhibitory rate of drug in 3LL is 19.14%, 33.59%, 40.63% and 51.56% respectively at dosage ranging from 100,150, 200 and 250 mg·kg^-1·d^-1. The drug inhibits tumor growth in a dose-dependent manner. The drug arrests 3LL cells in G₀-G₁ phase and decreases the expression of cyclin D1 protein. CONCLUSION:WMN inhibits the growth of 3LL cells in vivo by decreasing the expression of cyclin D1, blocking the cells in G₀-G₁ phase and preventing the cells transition from G₁ to S phase while DNA is replicated.