妊娠相关蛋白-A对自发性高血压大鼠左室肥厚的影响及γ-干扰素的干预作用  

Effect of the PAPP-A on left ventricular hypertrophy and the intervention of γ-interferon in the spontaneously hypertensive rat

作　　者：范剑峰[1] 郑春华[1] 汤圣兴[2] 高招波[1] 万明勇[1] 张春花[1] 张雪梅[1] 

机构地区：[1]南昌市第一医院(南昌大学第三附属医院)心血管二科,南昌330003 [2]皖南医学院附属弋矶山医院心内科

出　　处：《临床心血管病杂志》2011年第3期223-226,共4页Journal of Clinical Cardiology

摘　　要：目的:观察γ-干扰素(INF-γ)对自发性高血压大鼠(SHR)左心室肥厚(LVH)及妊娠相关蛋白-A(PAPP-A)的影响和干预作用。方法:SHR随机分为γ-干扰素高剂量组(SHR-H),中剂量组(SHR-M),低剂量组(SHR-L)和SHR对照组(SHR-C)(每组7只)。SHR-H、SHR-M、SHR-L分别用不同剂量的INF-γ干预8周。SHR-C组和7只正常大鼠对照组注射0.9%氯化钠溶液。观察治疗前、治疗第4周、第8周各实验大鼠尾动脉血压及血浆PAPP-A含量。实验第8周处死大鼠,称取大鼠左心室质量(LVM),计算左心室质量指数(LVMI);采用HE染色观察心肌的组织学变化;采用Western blot分析各实验大鼠心肌组织PAPP-A的表达。结果:①开始治疗前,SHR各组血压及PAPP-A浓度显著高于正常大鼠对照组(P<0.05)。SHR-H组使用INF-γ4周后、SHR-M组使用INF-γ8周后血压及PAPP-A浓度明显低于同时期的SHR-C组(P<0.05),但仍高于正常大鼠对照组(P<0.05)。②SHR各组LVM,LVMI都明显高于正常大鼠对照组(P<0.05)。与SHR-C组比较:使用INF-γ后SHR-H组LVM,LVMI明显下降(P<0.05)。③HE染色大鼠心肌组织可见正常大鼠对照组心肌细胞排列正常,间质无明显增生;SHR组心肌细胞体积增大,细胞排列紊乱;各用药组相对改善,以高剂量组最为明显。④PAPP-A与LVMI的相关分析显示PAPP-A与LVMI呈正相关(R=0.911,P<0.05)。⑤通过Westernblot检测可知:不同剂量INF-γ干预组和SHR-C组大鼠心肌组织PAPP-A表达水平显著高于正常大鼠对照组(P<0.05)。不同剂量INF-γ干预8周后,SHR-H组和SHR-M组大鼠心肌组织PAPP-A表达水平显著低于SHR-C组(P<0.05)。结论:PAPP-A在SHR心肌组织大量表达,INF-γ抑制PAPP-A的表达,具有剂量依赖性。Objective：To observe the effect of pregnancy-associated plasma protein-A（PAPP-A） on left ventricular hypertrophy（LVH） and the intervention of γ-interferon（INF-γ） in the spontaneously hypertensive rat（SHR）.Method：Twenty-eight SHR were randomly divided into 4 groups（n=7）： high-dose group（SHR-H）,middle dose group（SHR-M）,low-dose group（SHR-L） and the SHR control group（SHR-C）.SHR-L,SHR-M and SHR-H were injected INF-γ respectively for 8 weeks.SHR-C group and WKY group [7 Wistar-Kyoto（WKY） rats were selected as WKY control group（WKY,n=7）] were injected normal saline for 8 weeks.The tail arterial systolic blood pressure（SBP） of the rats and the level of PPAP-A were measured at the time of pre-therapy, 4 week of the treatment and 8 week.At the eighth week,they were sacrificed.We weighed the left ventricular of the hearts and calculated the left ventricular weight index.We observed the morphological changes in myocardial tissue with HE staining.The expression of PAPP-A protein was analysed by Western blot.Result：①At the time of pre-therapy,the different of SBP and PAPP-A was significantly higher in all SHR group than WKY group（P0.05）.After 4 weeks,SBP and PAPP-A in SHR-H group and after 8 weeks,SBP and PAPP-A in SHR-M was significantly lower than SHR-C group of the same time（P0.05）;but significantly higher than WKY group（P0.05）.②LVW and LVMI in all SHR group was significantly higher than WKY group（P0.05）.LVW and LVMI was decreased significantly after using high doses of INF-γ.③To observe HE stained sections by optical microscope： the normal myocardial cells,non-mesenchymal cells hyperplasia in WKY group.Myocardial cells and fibers was disorder in SHR group.This change of histology was inhibited in all group by usingINF-γ with the most effective in high-dose group.④The correlation analysis of PAPP-A and LVMI showed that they had a significant positive correlation（R=0.911,P0.05）.⑤Comparison with WKY group,the expression of PAPP-A in

关 键 词：高血压 妊娠相关蛋白-A 左室肥厚 Γ-干扰素 

分 类 号：R544.1[医药卫生—心血管疾病]