| Objective: To explore the relationship of vascular cell proliferation and apoptosis on vascular remodeling,to explore the relationship on AGES-RAGE and RAS, to explore the effect of AGES-RAGE and RAS on vascular remodeling , to explore the effect of combined treated with pyridoxamine and telmisartan on vascular remodeling by investigating blood pressure, vascular cell proliferation and apoptosis 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 12 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 , 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. The HE staining of myocardial tissue were detected by microscope. AI was detected by TUNEL. Extracellular signal-regulated kinase 1,2 (ERK1, ERK2)and PI 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 SBPCompared 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 level of serum No and SOD was lower in HC group (P <0.01). Compared with the HC group , the level of serum No and SOD was higher in T group,P group and TP group (P <0.05). Compared with the T group and P group , the level of serum No and SOD was higher in TP group (P <0.05).â‘¡Compared with the NC group ,the level of AGEs was higher in HC group (P <0.01). Compared with the HC group , the level of AGEs was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the level of AGEs was lower in TP group (P <0.05).â‘¢Compared with the NC group ,the level of AngII was higher in HC group (P <0.01). T group compared with the HC, the level of serum was higher (P <0.05).P group compared with the HC group the level of serum AngII concentration was lower (P <0.05), TP group compared with the T group, the level of serum the level of serum was lower(P <0.05).3,The results of microscope observation of myocardial tissue:VSMC arranged in neat rows in NC group. The cells had no significant hypertrophy compared with uniform nuclei size. Vessel wall intima was Smooth and internal elastic plate arranged rule. Extracellular collagen fiber was not obvious hyperplasia. VSMC of HC group cell arranged disorder. The cell hypertrophy, Vessel wall intima was coarse. elastic plate was fracture, and (or) bending.Extracellular collagen fibers hyperplasia. Compared with the HC group, T group, P group and TP group make progress in the indicators of cell proliferation, apoptosis, vascular intimal integrity and the proliferation of collagen fibers .4,The AI results:Cmpared with the NC group ,the level of AI was lower in HC group (P <0.01); Compared with the HC group , the level of AI was higher in T group,P group and TP group (P <0.05). Compared with the T group and P group , the level of AI was higher in TP group (P <0.05).5,Immunohistochemical results:Compared with the NC group ,the level of PI was higher in HC group (P <0.01); AS compared with the HC group , the level of PI was lower in T group,P group and TP group (P <0.05). AS compared with the T group and P group , the level of PI was lower in TP group (P <0.05). Compared with the NC group ,the level of ERK1,ERK2 was higher in HC group (P <0.01); Compared with the HC group , the level of ERK1,ERK2 was lower in T group,P group and TP group (P <0.05). Compared with the T group and P group , the level of ERK1,ERK2 was was lower in TP group (P <0.05).6,Real-time PCR detection of myocardial AT1, RAGE mRNA results:Compared with the NC group ,the level of AT1 mRNA of HC group was higher (P <0.01); Compared with the HC group , the level of AT1 mRNA of T group,P group and TP group was lower (P <0.05). Compared with T group and P group , the level of AT1 mRNA of TP group was was lower (P <0.05). Compared with the NC group ,the level of RAGE mRNA was higher in HC group (P <0.01). Compared with the HC group , the level of RAGE mRNA was lower in T group,P group and TP group (P <0.05). The level of RAGE mRNA between TP group and T group was not statistical significance.Conclusion:1, The hypertension pathological state induce the higher level of AGES in SHR compared with WKY. 2,The vascular cell proliferation and apoptosis is one of important factors in vascular remodeling.3, 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 vascular remodeling by reducing the level of AGES in SHR, improving the state of oxidative stress, conniving apoptosis and inhibiting proliferation . |
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