| Objective: To explore the relationship on myocardial remodeling with myocardial cell hypertrophy, hyperplasia and stromal fibrosis ,to explore the relationship on AGES-RAGE and RAS,to explore the effect of AGES-RAGE and RAS on myocardial remodeling ,to explore the effect of combined treated with pyridoxamine and telmisartan on myocardial remodeling by investigating blood pressure, myocardial cells and extracellular matrix on rats, which were combined treated with Telmisartan and Pyridoxamine.Methods: 48 spontaneously hypertensive rats (SHR) were randomly divided into four groups as hypertension experimental group. Each group have 12 rats. Hypertensive control group (HC group) was fed distilled water 2ml/d once time per day. Telmisartan group (T group) was fed telmisartan 6mg/kg/d once time per day. Pyridoxamine group (P group)was fed pyridoxamine hydrochloride 200 mg/kg/d once time per day. Combination therapy group (TP group) was fed telmisartan 6mg/kg/d and pyridoxamine 200 mg/kg/d once time per day.There were 13 Wistar Kyoto rats (WKY) in the normal control group (NC group), which were fed distilled water 2ml/d once time per day. Systolic blood pressure (SBP)of rat's tail was measured every 2 weeks. After 16 weeks of treatment , IVST,LVPWTd,EF% were detected through echocardiogram in all rats. Serum AGEs were detected by competitive ELISA. Serum angiotensin II (AngII) were detected by radioimmunoassay . Serum nitric oxide (NO) and superoxide dismutase (SOD) were detected by chemical method. Myocardial weight ratio were calculated. The HE staining of myocardial tissue were detected by microscope. Collagen volume fraction (CVF) of myocardial collagen were calculated by Picrosirius-picric acid staining. Extracellular signal-regulated kinase 1,2 (ERK1, ERK2) were measured through immunohistochemistry. The mRNA level of myocardial RAGE and angiotensin type 1 receptor (AT1) were detected by real-time PCR.Main Results:1,The results of SBP Compared with the NC group ,the value of SBP was significantly higher (P <0.01) in HC group; Compared with the HC group , the value of SBP was lower (P <0.01) in T group and TP group,no significant difference in P group (P>0.05);There was no significant difference between T group and P group (P>0.05).2,Blood serum hormones detectionâ‘ Compared with the NC group ,the leve of serum No and SOD was lower in HC group (P <0.01). Compared with the HC group , the leve of serum No and SOD was higher in T group,P group and TP group (P <0.05). Compared with the T group , the leve of serum No was higher in TP group (P <0.05). Compared with the P group , the leve of serum SOD was higher in TP group (P <0.05).â‘¡Compared with the NC group ,the leve of AGEs was higher in HC group (P <0.01). Compared with the HC group , the leve of AGEs was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the leve of AGEs was lower in TP group (P <0.05).â‘¢Compared with the NC group ,the leve of AngII was higher in HC group (P <0.01). T group compared with the HC, the leve of serum was higher (P <0.05).P group compared with the HC serum AngII concentration was lower (P <0.05), TP group compared with the T group, the leve of serum was lower(P <0.05).3,Heart weight ratio:Compared with the NC group ,the heart weight ratio was higher in HC group (P <0.01). Compared with the HC group , the heart weight ratio was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the heart weight ratio was lower in TP group (P <0.05). Compared with the NC group ,the EF% was lower in HC group (P <0.01).4,Ultrasound results:Compared with the NC group ,the IVSTd and LVPWTd was higher in HC group (P <0.01). Compared with the HC group , the IVSTd and LVPWTd was lower in of T group,P group and TP group (P <0.05). Compared with the T group and P group , the level of IVSTd and LVPWTd was lower in TP group (P <0.05). T group, P group, TP, HC group EF% had no significant difference (P> 0.05).5,The results of microscope observation of myocardial tissue:Myocardial cells arranged in neat rows in NC Group. The cells had no significant hypertrophy with uniform nuclei size. The collagen fibers which were outside the cell was not obvious proliferation. The myocardial cells disordered and hypertrophy in HC group. The collagen fibers which were outside the cell was multiplication. Compared with the HC group, T group, P group and TP group make progress in the indicators of myocardial cells hypertrophy and fibers hypertrophy.6,The CVF resultsCompared with the NC group ,the CVF was higher in HC group (P <0.01). Compared with the HC group , the CVF was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the leve CVF was was lower in TP group (P <0.05).7,Immunohistochemical results:Compared with the NC group ,the leve of ERK1and ERK2 was higher in HC group (P <0.01). Compared with the HC group , the leve of ERK1and ERK2 was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the leve of ERK1and ERK2 was lower in TP group (P <0.05).8,Real-time PCR detection of myocardial AT1, RAGE mRNA results:Compared with the NC group ,the leve of AT1 and RAGE was higher in HC group (P <0.01). Compared with the HC group , the leve of AT1 and RAGE was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the leve of AT1 and RAGE was lower in TP group was (P <0.05).Conclusion:1, The hypertension pathological state induce the higher level of AGES in SHR compared with WKY.2,The hypertrophy of myocardial cells and the multiplication of I,III collagen is one of important factor in myocardial remodeling3, AGEs-RAGE and the RAS are interacted with each other through oxidative stress mediated by ERLK1/2.4, Combined treatment with pyridoxamine and telmisartan have no significant synergy in antihypertension, but they can improve the myocardial remodeling by reducing the level of AGES in SHR, improving the state of oxidative stress, inhibiting cardiac hypertrophy and inhibiting proliferation of collagen fibers. |
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