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单核细胞趋化蛋白21 对高血压心肌纤维化的作用及其与转化生长因子2β的关系(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2004年第5期
页码:
417-420
栏目:
基础研究
出版日期:
2004-09-01

文章信息/Info

Title:
The role of mononuclear chemotaxis protein-1 on hypertensive rat myocardial f ibrosis and its relationship with transforming growth factor-β
作者:
王 斌赵连友郑强荪薛玉生李爱国姜艳华李言川于心亚尚福军陈军红杨静霄陈永清
第四军医大学唐都医院心血管内科,陕西西安710038
Author(s):
WANG Bin ZHAO Lian-you ZHENG Qiang-sun XUE Yu-sheng LI Ai-guo JIANG Yan-hua LI Yan-chuan YU Xin-ya SHANG Fu-jun CHEN Jun-hong YANG Jing-xiao CHEN Yong-qing
Department of Cardiology ,Tangdu Hospital ,Fourth MilitaryMedical University , Xi’an , Shaanxi 710038 ,China
关键词:
单核细胞趋化蛋白-1 转化生长因子-β心肌纤维化大鼠
Keywords:
mononuclear chemotaxis protein-1 transforming growth factor-β myocardial fibrosis rat
分类号:
R541. 3
DOI:
-
文献标识码:
A
摘要:
目的:研究单核细胞趋化蛋白21 (MCP21) 和转化生长因子2β(TGF2β) 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(L2NAME) 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RT2PCR 测定大鼠心脏组织内MCP21 与TGF2β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。7 d 组、14 d 组和28 d 组的胶原容积分数(CVF) 与对照组比较均有显著性差异( P < 0. 05) ;7 d 组、14 d 组和28 d 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. 05) 。③MCP21 mRNA 水平在给药后第3 d 有明显升高,随后逐渐下降。3 d 组、7 d 组,14 d 组和28 d 组的的MCP21 mRNA 的水平与对照组比较均有显著性差 异( P < 0. 05) 。④TGF2βmRNA 水平在慢性阻断NOS 后7 d 显著升高,随后维持于较高水平直至第28 d。7 d 组、14 d 组和28 d 组TGF2βmRNA 的水平与对照组比较均有显著性差异( P < 0. 05) ,3 d 组TGF2βmRNA 的水平与对照组比 较无显著性差异( P > 0. 05) 。结论: ①MCP21 和TGF2β均参与高血压心肌纤维化的发生发展。②MCP21 可能是高血 压心肌纤维化的启动因素,TGF2β可能对促进和维持高血压心肌纤维化起重要作用。
Abstract:
AIM: To investigate the effects of inflammatory factor mononuclear chemotaxis protein-1 (MCP-1) and transforming growth factor-β(TGF2β) on myocardial fibrosis during hypertension induced by Nω-nitro-L- arginine methyl ester (L-NAME) administration by observing the fibrosis in the rat heart and the expression of MCP-1 and TGF-βin the heart in order to study the role of inflammation in hypertensive myocardial fibrosis. METHODS : The model of hypertension was established by administration of L-NAME. Fibrosis was evaluated morphometrically. The charactistics of the cardiac muscle were observed with the histological method. MCP-1 and TGF-βwere determined by the reverse transcription polymerase chain reaction at the transcriptional level . RESULTS : ①Chronic inhibition of nitric oxide synthase (NOS) increased arterial pressure compared with the control group. ②Chronic inhibition of NOS caused significant interstitial fibrosis and perivascular fibrosis. Collagen volume fractions(CVF) of the 7-day group , 14-day group and 28-day group were 4. 45 %±0. 20 % , 5. 42 % ±0. 68 % and 7. 02 %±0. 82 % respectively , which were significantly different from that of the control group (3. 12 % ±0. 08 %) ( P < 0. 05) ; Perivascular collagen areas (PVCA) were 0. 85 % ±0. 09 % ,1.18 %±0. 16 % and 1. 52 %±0. 20 % respectively , which were significantly different from that of the control group (0. 51 % ±0. 05 %) ( P < 0. 05) . ③A markedly increased expression of MCP-1 mRNA was observed in the heart tissue on the 3rd day of the treatment and declined with the further L-NAME administration. The levels of MCP-1 mRNA of the 3-day group , 7-day group , 14-day group and 28-day group were 0. 82 ±0. 12 , 0. 38 ±0. 06 , 0. 31 ±0. 05 and 0. 22 ±0. 02 respectively , which were significantly different from that of the control group (0. 11 ±0. 01) ( P < 0. 05) . ④The expression of TGF-βmRNA was increased during chronic inhibition of NOS and sustained at the high level until the 28th day. The level of TGF-βmRNA were 1. 13 ±0. 08 , 1. 52 ±0. 17 and 1. 46 ±0. 12 respectively , which were significantly different from that of the control group(0. 18 ±0. 02) ( P < 0. 05) . There was no significant difference between the 3-day group (0. 21 ±0. 03) and the control group (0. 18 ±0. 02) ( P > 0. 05) . CONCLUSION: ①MCP-1 and TGF-βmay be involved in the fibrosis during hypertension. ②MCP-1 may play an important role in the initiating fibrosis during hypertension. ③ TGF-βmay play an important role in the chronic development of the myocardial fibrosis in essential hyperten2 sion.

参考文献/References

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[3 ] Yang XD , Zhao LY, Zheng QS , et al . Effects of arginine vasopressin on growth of rat cardiac fibroblasts : role of V1 receptor [J ] . J Cardiovasc Pharmacol , 2003 , 42 (1) : 132 - 135.

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[5 ] 赵连友,李宏伟,李 雪,等. 高血压病患者血管平滑肌一氧化氮合酶活性变化和精氨酸加压素对一氧化氮合成的影响[J ] . 中华医学杂志, 2000 , 80 (6) : 425 - 428.

备注/Memo

备注/Memo:
收稿日期:2003-12-22
更新日期/Last Update: 2004-09-01