CAJ | 학술논문

目的：对比研究肾上腺髓质素(Adrenomedullin ADM)对自发性高血压大鼠(spontaneously hypertensive rat SHR)心脏重构的影响及与ERK1/2活化的关系。方法：4周龄雄性SHR随机分为SHR组和SHR-T组,同周龄WKY大鼠作为正常对照。SHR-T组皮下注射ADM(每周5天,1.0nmol/(kg.d)),SHR组皮下注射等体积生理盐水,WKY组不作处理。在第4、8、16和24周龄时间点分别处死动物(每组4只),提取心脏做H.E染色和P-ERK1/2免疫组化染色。结果：SHR组和SHR-T组从8周龄开始血压显著升高,明显高于WKY组(P<0.01),ADM治疗至24周龄时,血压明显低于SHR组；随着大鼠周龄增加,SHR组和SHR-T组大鼠心脏/体重比值逐渐增大。16周龄后,SHR组和SHR-T组的心脏/体重比值大于WKY组(P<0.05),24周龄SHR-T组大鼠的心脏/体重比值小于SHR组(P<0.05)；随着大鼠周龄增加, SHR和SHR-T组大鼠相对左心室壁厚度呈增加趋势,24周龄SHR组大鼠相对左心室壁厚度大于同周龄WKY组(P<0.05)。SHR-T组大鼠相对左心室壁厚度在16周龄后增幅放缓,24周龄时小于SHR组(P<0.05)；随着大鼠周龄的增加p-ERK1/2在大鼠心肌中的阳性表达逐渐增加,24周龄SHR组大鼠心脏p-ERK1/2的表达率显著高于WKY组(P<0.01),24周龄SHR-T组大鼠心脏p-ERK1/2的表达率显著低于SHR组(P<0.05)。结论：ADM可一定程度减缓自发性高血压大鼠血压的升高和心脏重构,p-ERK1/2的表达量的降低可能参与了ADM发挥其保护作用。
목적：대비연구신상선수질소(Adrenomedullin ADM)대자발성고혈압대서(spontaneously hypertensive rat SHR)심장중구적영향급여ERK1/2활화적관계。방법：4주령웅성SHR수궤분위SHR조화SHR-T조,동주령WKY대서작위정상대조。SHR-T조피하주사ADM(매주5천,1.0nmol/(kg.d)),SHR조피하주사등체적생리염수,WKY조불작처리。재제4、8、16화24주령시간점분별처사동물(매조4지),제취심장주H.E염색화P-ERK1/2면역조화염색。결과：SHR조화SHR-T조종8주령개시혈압현저승고,명현고우WKY조(P<0.01),ADM치료지24주령시,혈압명현저우SHR조；수착대서주령증가,SHR조화SHR-T조대서심장/체중비치축점증대。16주령후,SHR조화SHR-T조적심장/체중비치대우WKY조(P<0.05),24주령SHR-T조대서적심장/체중비치소우SHR조(P<0.05)；수착대서주령증가, SHR화SHR-T조대서상대좌심실벽후도정증가추세,24주령SHR조대서상대좌심실벽후도대우동주령WKY조(P<0.05)。SHR-T조대서상대좌심실벽후도재16주령후증폭방완,24주령시소우SHR조(P<0.05)；수착대서주령적증가p-ERK1/2재대서심기중적양성표체축점증가,24주령SHR조대서심장p-ERK1/2적표체솔현저고우WKY조(P<0.01),24주령SHR-T조대서심장p-ERK1/2적표체솔현저저우SHR조(P<0.05)。결론：ADM가일정정도감완자발성고혈압대서혈압적승고화심장중구,p-ERK1/2적표체량적강저가능삼여료ADM발휘기보호작용。
Objective: Comparative study the protect effect of Adrenomedullin(ADM) on cardiac remodeling of SHR and It's relationship with activation of ERK1/2. Methods:The 4-week-old male spontaneously hypertensive rats (SHR) were randomly divided into SHR group and SHR-T(SHR treatment) group, age matched WKY rats served as normal controls. Subcutaneous injection of ADM (SHR-T,5 days/week, 1.0 nmol / (kg.d)), SHR group subcutaneous injection of an matched volume of saline. No special treatment to control WKY group. The animals (n=4) were sacrificed at 4,8,16 and 24 weeks of age and the heart was collected for HE staining and p-ERK1/2 immunohistochemical staining. Results: Beginning from 8 weeks of age, blood pressure of SHR group and SHR-T group increased, significantly higher than WKY group (P<0.01). After treatment of ADM for 24 weeks, blood pressure of SHR was significantly lower than the untreated SHR group. The heart/body weight ratio of the SHR group and SHR-T group rat increased gradually with the age increase, greater than age-matched WKY group after 16 weeks of age (P<0.05). However, the heart/body weight ratio of 24-week-old SHR-T group of rats is less than the SHR group (P<0.05). With the age increase, the relative left ventricular wall of SHR and SHR-T rats become thickness comparing with the WKY rats. The relative left ventricular wall thickness of 24-week-old SHR rats greater than the same week-old WKY group (P<0.05). The relative left ventricular wall thickness of SHR-T growth slower after 16 weeks of age, less than untreated SHR group at 24 weeks of age (P<0.05). The positive expression of p-ERK1/2 in the myocardium gradually increased as the rats grow, and at 24-week-old SHR rats, the expression was significantly higher than WKY group (P<0.01). However, the cardiac p-ERK1/2 expression rate at 24-week-old SHR-T group was significantly lower than that in SHR group (P<0.05). Conclusion:To a certain extent, ADM might can slow the increase of blood pressure and cardiac remodeling in SHR. Reduction of p-ERK1/2 expression might be involved in the protective effect of ADM.