单核细胞趋化蛋白-1对高血压心肌纤维化的作用及其与转化生长因子-β的关系

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目的 :研究单核细胞趋化蛋白 1(MCP 1)和转化生长因子 β(TGF β)对高血压心肌纤维化的影响 ,探讨炎性反应在高血压心肌纤维化发生发展中的作用。方法 :用左旋硝基精氨酸甲酯 (L NAME)喂饲建立高血压模型。用组织学的方法评估心肌纤维化的程度和RT PCR测定大鼠心脏组织内MCP 1与TGF β的mRNA水平。 结果 :①慢性阻断一氧化氮合酶 (NOS)活性显著升高大鼠尾动脉血压。②慢性阻断NOS活性可引起心脏间质纤维化和血管周围纤维化。 7d组、14d组和 2 8d组的胶原容积分数 (CVF)与对照组比较均有显著性差异 (P <0 .0 5 ) ;7d组、14d组和 2 8d组的血管周围胶原面积 (PVCA)与对照组比较均有显著性差异 (P <0 .0 5 )。③MCP 1mRNA水平在给药后第 3d有明显升高 ,随后逐渐下降。 3d组、7d组 ,14d组和 2 8d组的的MCP 1mRNA的水平与对照组比较均有显著性差异 (P <0 .0 5 )。④TGF βmRNA水平在慢性阻断NOS后 7d显著升高 ,随后维持于较高水平直至第 2 8d。 7d组、14d组和 2 8d组TGF βmRNA的水平与对照组比较均有显著性差异 (P <0 .0 5 ) ,3d组TGF βmRNA的水平与对照组比较无显著性差异 (P >0 .0 5 )。结论 :①MCP 1和TGF β均参与高血压心肌纤维化的发生发展。②MCP 1可能是高血压心肌纤维化的启动因素 ,TGF β可能对? Objective: To investigate the effects of monocyte chemoattractant protein 1 (MCP 1) and transforming growth factor beta (TGF-β) on myocardial fibrosis in hypertensive rats and to explore the role of inflammatory response in the development of hypertensive myocardial fibrosis. Methods: Hypertensive model was established by feeding L-NAME. The extent of myocardial fibrosis was assessed by histological methods and the mRNA levels of MCP 1 and TGFβ in rat heart tissue were determined by RT-PCR. Results: ① Chronic blockade of nitric oxide synthase (NOS) activity significantly increased the tail arterial pressure in rats. ② chronic block of NOS activity can cause cardiac interstitial fibrosis and perivascular fibrosis. Collagen volume fraction (CVF) in 7d group, 14d group and 28d group were significantly different from those in control group (P <0.05). Perivascular collagen area (PVCA) in 7d group, 14d group and 28d group ) Compared with the control group were significantly different (P <0. 05). ③ The level of MCP1 mRNA increased significantly on the 3rd day after administration, and then decreased gradually. The levels of MCP 1 mRNA in 3d, 7d, 14d and 28d groups were significantly different from those in control group (P <0.05). ④TGF β mRNA levels were significantly increased at 7 days after chronic blockade of NOS, and then maintained at a high level until the 28th day. The levels of TGFβ mRNA in 7d group, 14d group and 28d group were significantly different from those in control group (P <0.05). The levels of TGFβ mRNA in 3d group were not significantly different from those in control group (P> 0.05). 0 5). Conclusion: ①MCP 1 and TGF β are involved in the occurrence and development of hypertensive myocardial fibrosis. ② MCP 1 may be the initiating factor of hypertensive myocardial fibrosis, TGF β may be?
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