摘要
目的 :探讨细胞增殖与细胞凋亡在高血压左室肥厚中的作用及血管紧张素Ⅱ 1型受体 (AT1受体 )拮抗剂在体干预对其影响。方法 :选用成年 12及 2 4周龄SHR和WKY大鼠 ,干预组SHR自 12周龄起每日胃管灌饲losartan ( 15mg·kg-1·d-1)至 2 4周龄止。称重法测量左室肥厚指数 ,免疫组化法检测PCNA的蛋白表达 ,TUNEL法原位检测细胞凋亡 ,半定量RT -PCR法检测fasmRNA表达。结果 :SHR左室肥厚指数、心肌细胞凋亡率显著多于同龄WKY(P <0 0 1) ,心肌成纤维细胞凋亡率显著低于同龄WKY(P <0 0 5 )。 12周龄SHR心肌细胞PCNA阳性率显著高于同龄WKY(P <0 0 5 ) ,心肌成纤维细胞阳性率在两组间无显著差异。 2 4周龄WKY和干预组SHR无PCNA阳性细胞检出 ,2 4周龄SHR偶见阳性心肌细胞。干预组左室肥厚指数、心肌细胞凋亡率显著低于同龄SHR组 ,成纤维细胞凋亡率显著高于同龄SHR组。各组大鼠心肌组织中fasmRNA表达量与细胞凋亡率呈正相关 (r=0 5 2 ,P <0 0 5 )。结论 :成年SHR左室肥厚的细胞学变化表现为心肌细胞的增殖 /凋亡的失衡 ,以及心肌成纤维细胞凋亡的减少。
AIM: To investigate the role of proliferation and apoptosis in hypertensive left ventricular hypertrophy (LVH) and the effect of AT 1 blockade with losartan. METHODS: Left ventricles (LV) from 12, 24-week-old SHR (SHR 12 , SHR 24 ), 24-week-old SHR treated with losartan (15 mg·kg -1 ·d -1 , SHR-L 24 ) during 12 weeks, and age-matched WKY rats (WKY 12 , WKY 24 ) were studied. Expression of PCNA was examined by immunohistochemistry. Apoptotic cells in LV sections were assessed by TUNEL method. Levels of fas mRNA were quantitated by RT-PCR. RESULTS: Compared with age-matched WKY, SHR 12 and SHR 24 showed increased LV hypertrophied index (HI), increased apoptotic index (AI) of myocytes ( P< 0.01), but decreased AI of fibroblasts ( P< 0.05). Moreover, SHR 12 exhibited increased PCNA labeling of myocytes ( P< 0.05) with similar positive rates of fibroblasts.It was also showed that losartan reversed HI, significantly reduced the AI of myocytes and significantly increased the AI of fibroblasts. RT-PCR disclosed that levels of fas mRNA positively correlated with the frequency of apoptosis in LV of either SHR or WKY ( r= 0.52, P< 0.05). CONCLUSION: The cellular changes of LVH in adult SHR manifest as the imbalance between proliferation and apoptosis of myocytes, and insufficient apoptosis of fibroblasts. The mechanisms of losartan on reversing LVH may be mediated through adjusting the abnormal amount of cells and the expression of fas gene.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2002年第2期120-123,共4页
Chinese Journal of Pathophysiology
基金
国家教委留学回国人员科研基金资助
关键词
心肌病
血管紧张素
高血压
细胞增殖
细胞凋亡
Cardiomyopathy, hypertrophic
Apoptosis
Receptors, angiotensin
Hypertension