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肾上腺髓质素对自发性高血压大鼠肾脏微小动脉的影响
引用本文:魏少民,张建忠,杨玲娣,常越,郭凤英,景丽. 肾上腺髓质素对自发性高血压大鼠肾脏微小动脉的影响[J]. 南方医科大学学报, 2014, 34(8): 1140-1144
作者姓名:魏少民  张建忠  杨玲娣  常越  郭凤英  景丽
作者单位:1. 宁夏医科大学基础医学院病理学系,宁夏银川750004;内蒙古阿拉善盟中心医院病理科,内蒙古巴彦浩特750306
2. 宁夏医科大学基础医学院病理学系,宁夏银川,750004
3. 宁夏回族自治区人民医院病理科,宁夏银川,750021
基金项目:教育部重点项目(项目编号:210242)教育部春晖计划项目(项目编号:2002100104)宁夏医科大学研究项目(项目编号:KF2010-26,XT2011009)
摘    要:
目的探讨肾上腺髓质素(Adrenomedullin, ADM)对自发性高血压大鼠(SHR)肾脏微小动脉的影响及与磷酸化细胞外调
节蛋白激酶1/2(ERK1/2)的关系。方法4周龄雄性SHR随机分为ADM治疗组(ADM组)和高血压对照组(SHR组),以WKY
大鼠作为空白对照,ADM组皮下注射ADM(1.0 nmol/kg·d,每周5 d)。采用组织学、组织化学、免疫组织化学和Western blot技
术,对比观察平均动脉收缩压、肾微小动脉组织学变化和磷酸化ERK1/2表达。结果从8周龄开始,SHR和ADM组血压开始升
高,16和24周龄平均动脉收缩压明显高于WKY组,ADM治疗组24周龄时平均动脉收缩压明显低于非治疗SHR组;在16和24
周龄,SHR组和ADM组大鼠肾脏微小动脉中膜/内径比值明显大于WKY组(P<0.05);ADM组大鼠肾脏微小动脉中膜/内径比
值的增幅略低于SHR组,其中外径小于40 μm动脉中膜/内径比值在24 周龄时明显小于SHR组(P<0.05)。免疫组织化学和
Western blot显示16和24周龄SHR和ADM组大鼠肾脏组织磷酸化ERK1/2表达显著高于WKY组(P<0.05),24周龄时ADM组
肾脏磷酸化ERK1/2表达显著低于SHR组(P<0.05)。结论较长时间使用ADM,在一定程度上能够减轻自发性高血压大鼠血
压升高程度,可能通过抑制ERK1/2的磷酸化减轻肾微小动脉的重构。


关 键 词:肾上腺髓质素  高血压  自发性高血压大鼠  微小动脉  细胞外调节蛋白激酶

Effect of adrenomedullin on renal arteriole remodeling in spontaneous hypertensive rats
WEI Shaomin , ZHANG Jianzhong , YANG Lingdi , CHANG Yue , GUO Fengying , JING Li. Effect of adrenomedullin on renal arteriole remodeling in spontaneous hypertensive rats[J]. Journal of Southern Medical University, 2014, 34(8): 1140-1144
Authors:WEI Shaomin    ZHANG Jianzhong    YANG Lingdi    CHANG Yue    GUO Fengying    JING Li
Abstract:
Objective To investigate the effect of adrenomedullin (ADM) on renal arteriole remodeling and phosphorylation of
extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in spontaneous hypertensive rats (SHR). Methods Male SHR (4
weeks old) were randomized into hypertensive group (SHR) and ADM-treated group (ADM) to receive subcutaneous saline
and ADM injections (daily dose of 1.0 nmol/kg, 5 days a week), respectively, with age-matched Wistar-Kyota (WKY) rats as the
blank control. The systolic blood pressure (SBP) was measured at the end of each week, and histological changes of the renal
arterioles were observed using HE and Weigert staining; the expression of P-ERK1/2 in the arterioles was detected with
immunohistochemistry and Western blotting. Results At 16 and 24 weeks of age, the rats in both SHR and ADM groups
showed significantly higher SBP levels than WKY rats (P<0.05), and at 24 weeks, SBP was significantly lower in ADM group
than in SHR group (P<0.05). The intima thickness/lumen diameter (IT/LD) ratio of the renal arterioles increased in both SHR
and ADM groups at 16 and 24 weeks as compared with that of WKY rats (P<0.05), and for arterioles with an outer diameter <40
μm, the IT/LD ratio was significantly lower at 24 weeks in ADM group than in SHR group (P<0.05). The renal expression of
p-ERK1/2, which increased significantly in SHR and ADM groups at 16 and 24 weeks (P<0.05), was significantly lower in ADM
group than in SHR group at 24 weeks (P<0.05). Conclusions Long-term ADM treatment can control SPB elevation in SHR rats
and reduce renal arteriole remodeling by inhibiting the phosphorylation of ERK1/2.
Keywords:adrenomedullin  hypertension  spontaneously hypertensive rat  arteriole  extracellular signal-regulated protein
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