大鼠心肌肥厚时心脏心钠素、ras癌基因的表达

EXPRESSION OF ANP AND RAS GENE IN MYOCARDIAC HYPERTROPHY OF RATS

心钠素是由心肌细胞合成和分泌的一种循环激素，具有强大的利钠、利尿、舒张血管、抑制肾素—血管紧张素系统等作用，在高血压、心肾功能不全等疾病的发病过程中具有重要作用。本工作采用分子杂交技术，研究了心室超负荷、高血压心肌肥厚时，大鼠心肌心钠素基因以及ｒａｓ癌基因的表达。实验证明：ａ，部分结扎肾动脉上方的腹主动脉可明显升高血压和左心室／体重比值；血浆心钠素水平可由未结扎时的１２７．００士２１．８ｐｇ／ｍｌ升至结扎１周时的４６１．１０士１０２．９０ｐｇ／ｍｌ（Ｐ＜０．０１）。ｂ．Ｎｏｒｔｈｅｒｎｂｌｏｔ结果发现，心房心钠素ｍＲＮＡ在腹主动脉部分结扎后１周内没有明显的改变，两周时明显升高；心室心钠素ｍＲＮＡ在结扎１周时开始出现，４周时达到高峰。牛磺酸可明显促进心室心钠素ｍＲＮＡ的表达，肼苯哒嗪则明显抑制心室心钠素的转录。ｃ．应用心钠素限制性内切酶片段长度多态性分析，还发现遗传性高血压大鼠的染色体ＤＮＡ应用ＰｓｔＩ酶切后，较ＷＫＹ大鼠缺失一条３．０ｋｂ的片段。ｄ．部分结扎腹主动脉或注射α－肾上腺素能受体激动剂—新福林，可促进心肌ｒａｓ癌基因的转录。这种增加在结扎后４小时内即可发生，且可持续３周以上。其ｒａｓｍＲＮＡ的变化?

NP is a circulatory hormone synthesized and secreted by myocardial cells,It exerts as a powerful hor-mone with natriuretic, diuretic,vasodilatory effect and inhibits Renin-Angitensin system。It plays an impor-tant r le in the hypertension,heart dysfunction and renal dysfunction。This work reported here the gene ex-pression of cardiac ANP in heart pressure overload and myocardiac hypertrophy of rats in hypertensive state by using molecular hybridization。The results of the experiments indicated that:a)By abdominal aortic coarctation of the rats,blood pressure and left ventricular weight /body weight ratio increased significantly;plasma ANP level increased to 461.10±l02.90 pg/ml at the end of one week from unbanded l27.00± 2l.8 pg/ml( p<0.01).(b) Northern blot indicated that in the first week of banding, the atrial ANP mRNA was unchanged;whereas in the second week it increased significantly.Ventricular ANP mRNA occured in the first week of banding and reached the peak value in the forth week.Taurine could increase the expression ofANP mRNA significantly in the contrast,hydralazine significantly inhibited the ANP gene expressiion.(c)By the techniques of RFLPs analysis of ANP,we found that after the genomic DNA was digested wiht PstI,the spontaneously hypertensive rats missed a 3.0 kb fragment compared with their normal control WKY rats。The above results indicate that both the expression and transcription of ANP gene increased in myocardiac hy-pertrophy. In SHR there may have structural difference of ANP gene compared with WKY rats.(d) Using the method of molecular hybridization,we also found that the expression of cardial proto-oncogene ras in-creased both in abdominal aortic coarctation rats or the rats which were injected α-adrenergic receptor ago-nist nersynephrine. The increased expression occured after 4hours of banding and persisted at least 3 weeks. The change of ras mRNA level occured before that of ANP,suggestion that it may be a medium or initial fac-tor of both myocardiac hypertrophy and the expression of ANP gene.