复合离子盐对两肾一夹高血压大鼠左心室心肌肥厚和纤维化的影响及其机制的初步探讨

Effects and mechanism of compound ion salt on myocardial hypertrophy and fibrosis of two kidney-one clamp renal hypertensive rat

目的研究复合离子盐对两肾一夹高血压大鼠左心室心肌肥厚和纤维化的影响并初步探讨其发生机制。方法将80只Wistar大鼠喂含8%普通盐饲料1周后,70只行二肾一夹经典造模,10只行假手术。将造模成功的大鼠随机分为5组:复合离子盐组、缬沙坦组、环孢菌素A组、普通加碘盐组和假手术组。12周后,测量并比较各组收缩压、左心室质量与胫骨长度比值(Lvw/TL)、胶原总面积/图象总面积(CVF)、心钠素(ANP)、左心室磷酸酶mRNA、c-fosmRNA表达水平,以及左心室磷酸酶mRNA与Lvw/TL、CVF和ANP的相关性。结果复合离子盐组ANP、CVF、Lvw/TL水平显著低于普通加碘盐组,ANP(72.71±34.98)ng/g vs(231.89±32.51)ng/g(P<0.01);CVF(15.73±1.40)%vs(18.60±2.20)%(P<0.01);Lvw/TL(26.33±3.95)g/m vs(34.15±6.55)g/m(P<0.01)。缬沙坦组ANP、CVF、Lvw/TL水平显著低于普通加碘盐组,ANP为(66.63±31.34)ng/g vs(231.89±32.51)ng/g(P<0.01);CVF(8.16±0.80)%vs(18.60±2.20)%(P<0.01);Lvw/TL(24.82±2.68)g/m vs(34.15±6.55)g/m(P<0.01)。环孢菌素A组ANP、CVF、Lvw/TL水平显著低于普通加碘盐组,ANP(127.80±31.08)ng/g vs(231.89±32.51)ng/g(P<0.01);CVF(16.47±2.06)%vs(18.60±2.20)%(P<0.01);Lvw/TL(29.83±4.99)g/m vs(34.15±6.55)g/m(P<0.05);复合离子盐组左心室CVF水平显著高于缬沙坦组(P<0.01);环孢菌素A组ANP、CVF水平显著高于缬沙坦组(P<0.01);复合离子盐组ANP水平低于环孢菌素A组(P<0.05)。普通加碘盐组左心室磷酸酶mRNAc、-fos mRNA表达水平显著高于假手术组,磷酸酶mRNA 0.96±0.12 vs 0.62±0.06(P<0.01),c-fos mRNA 140.98±19.41 vs 92.11±17.89(P<0.01);复合离子盐组、缬沙坦组、环孢菌素A组左心室磷酸酶mRNAc、-fos mRNA水平显著低于普通加碘盐组,磷酸酶mRNA 0.82±0.10、0.69±0.08、0.62±0.09 vs 0.96±0.12(P<0.01),c-fos mRNA 128.84±15.95、106.92±14.71、107.31±13.96 vs 92.11±17.89(P<0.01);复合离子盐组左心室磷酸酶mRNA、c-fos mRNA水平显著高于缬沙坦组(P<0.05或<0.01);Lvw/TL,ANP和CVF与磷酸酶mRNA表达水平呈显著正相关(r=0.735、0.580、0.676,均P<0.01)。结论复合离子盐能够改善高血压性心肌肥厚,其作用机制同降低磷酸酶mRNAc、-fos mRNA表达水平相关。

Objective To study the effects and mechanism of compound ion salt on myocardial hypertrophy and fibrosis of two kidney-one clamp renal hypertensive rat.Methods After duplicating the model of two kidney-one clamp renal hypertensive rats,we treated the rats with compound ion salt,valsartan and cycloslporine（CsA） in different groups respectively for 12 weeks.We detected and compared 12 indexes such as systolic blood pressure,Lvw/TL,CVF,ANP,calcineurin mRNA,c-fos mRNA and so on.Results Compared with common salt,compound ion salt had significant effects on ameliorating and retroconversing the left ventricuar remodeling process caused by hypertension,Lvw/TL（26.33±3.95） g/m vs（34.15±6.55） g/m（P0.01）,CVF（15.73±1.40）% vs（18.60±2.20）%（P0.01）,ANP（72.71±34.98） ng/g vs（231.89±32.51） ng/g（P0.01）.Calcineurin mRNA 0.82±0.10 vs 0.96±0.12（P0.01）;Compared with common salt,valsartan also had similar effects,Lvw/TL（24.82±2.68） g/m vs（34.15±6.55） g/m（P0.01）,CVF（8.16±0.80）% vs（18.60±2.20）%（P0.01）,ANP（66.63±31.34） ng/g vs（231.89±32.51） ng/g（P0.01）,calcineurin mRNA0.69±0.08 vs 0.96±0.12（P0.01）,c-fos mRNA 106.92±14.71 vs 140.98±19.41（P0.05）.With regard to the effects on ameliorating and retroconversing the left ventricular remodeling process caused by hypertension,CsA had displayed significant effects comparing to common salt,CVF（16.47±2.06）% vs（18.60±2.20）%（P0.01）,Lvw/TL（29.83±4.99） g/m vs（34.15±6.55） g/m（P0.05）,ANP（127.80±31.08） ng/g vs（231.89±32.51） ng/g（P0.01）.Calcineurin mRNA 0.62±0.09 vs 0.96±0.12（P0.01）,c-fos mRNA107.31±13.96 vs 140.98±19.41（P0.01）.Compared with valsartan,compound ion salt＇s effects on ameliorating and retroconversing the left ventricular remodeling process caused by hypertension were weaker,CVF（15.73±1.40）% vs（8.16±0.80）%（P0.01）.Calcineurin mRNA was 0.82±0.10 vs 0.69±0.08（P0.01）,c-fos mRNA was 128.84±15.95 vs 106.92±14.71（P0.05）.Conclusion Compound ion salt can ameliorate the left ventricular remodeling process caused by hypertension,its mechanism had correlation to decrease the level of calcineurin mRNA,c-fos mRNA.