天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (5): 370-374.doi: 10.11958/20193104

• 实验研究 • 上一篇    下一篇

SHR大鼠肾组织AngⅡ和TGF-β/Smads水平变化与肾纤维化的关系及依那普利干预效果

陈万里 1，2，李慧慧 1，2，朱振宇 1，2，黄安安 2，3，柳占彪 1，齐新 2△
  

  1. 1天津中医药大学研究生院（邮编301617）；2天津市人民医院心脏科；3南开大学医学院

  • 收稿日期:2019-10-17 修回日期:2020-03-31 出版日期:2020-05-15 发布日期:2020-06-24
  • 通讯作者: 齐新 E-mail:qixinx2011@126.com
  • 作者简介:陈万里（1993），男，硕士在读，主要从事高血压致肾损害方面研究
  • 基金资助:
    天津市科委慢性疾病防治科技重大专项（16ZXMJSY00060）

Relationship between changes of Ang II and TGF-β/Smads levels and renal fibrosis in SHR rats and the intervention effect of Enalapril

CHEN Wan-li1, 2, LI Hui-hui1, 2, ZHU Zhen-yu1, 2, HUANG An-an2, 3, LIU Zhan-biao1, QI Xin2△ #br#   

  • Received:2019-10-17 Revised:2020-03-31 Published:2020-05-15 Online:2020-06-24
  • Contact: QI Xin E-mail:qixinx2011@126.com

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摘要： 摘要：目的 探讨依那普利对自发性高血压大鼠（SHR）肾组织血管紧张素Ⅱ（AngⅡ）和TGF-β/Smads通路相关因
子mRNA表达的影响。方法 20只雄性SHR随机分成模型组和依那普利组；另取雄性Wistar-Kyoto（WKY）大鼠10只
作为对照组。依那普利组给药剂量为1.05 mg/ （kg·d），每日1次灌胃，持续10周，模型组和对照组灌胃等量生理盐水。
每2周监测1次血压，10周后处死动物并取材。使用脲酶法检测各组大鼠血尿素氮（BUN）水平，采用酶联免疫吸附测
定（ELISA）i法检测各组AngⅡ、血清胱抑素C（CysC）、尿微量白蛋白（mALB）水平，Masson染色观察大鼠肾组织病理变
化，实时荧光定量PCR检测肾组织中AngⅡ、转化生长因子β1（TGF-β1）、Smad2、Smad3、Ⅰ型胶原（CollagenⅠ）和Ⅳ型
胶原（CollagenⅣ）的mRNA相对表达量。结果 给药前（0周），与对照组相比，模型组和依那普利组大鼠收缩压与舒张
压均显著升高（P＜0.05）；与模型组比较，依那普利组收缩压与舒张压差异无统计学意义（P＞0.05）；药物干预后，与模
型组比较，依那普利组的收缩压与舒张压均显著下降（P＜0.05）。与对照组比较，模型组AngⅡ、BUN、CysC和尿mALB
水平明显升高（P＜0.05）；肾组织出现大量蓝色胶原纤维沉积，同时AngⅡ、TGF-β1、Smad2、Smad3、CollagenⅠ和Collagen
Ⅳ的mRNA相对表达量明显升高（P＜0.05）。与模型组相比，依那普利组肾组织胶原纤维沉积程度明显减轻，血清及肾
组织中上述指标均明显下降（P＜0.05）。结论 依那普利可对SHR起到稳定的降压作用，并通过降低AngⅡ的水平、抑
制TGF-β/Smads信号通路的表达，减轻肾纤维化，改善高血压导致的肾损伤。

关键词: 依那普利；大鼠, 近交SHR；血管紧张素Ⅱ；转化生长因子β；肾纤维化

Abstract: Abstract: Objective To investigate the effect of enalapril on angiotensin (Ang) Ⅱ and TGF-β/Smads in renal tissue
of spontaneously hypertensive rats (SHR). Methods A total of 20 male SHRs were randomly divided into model group and
enalapril group. Ten male Wistar Kyoto rats (WKY) were taken as control group. The dosage of enalapril was 1.05 mg/(kg·d),
once a day, for 10 weeks. The model group and the control group were given the same amount of normal saline. Blood
pressure was monitored every two weeks regularly. After 10 weeks animals were killed and tissue samples were collected.
Urease method was used to detect the blood urea nitrogen (BUN) content. Enzyme-linked immunosorbent assay (ELISA) was
used to detect the contents of Ang Ⅱ, serum cystatin C (CysC) and urinary microalbumin (mALB). Masson staining was used
to observe the renal pathological changes. Real-time PCR was used to detect the relative mRNA expressions of Ang Ⅱ ,
transforming growth factor β1(TGF-β1), Smad2, Smad3, CollagenⅠ and Collagen Ⅳ. Results Compared with the control
group, the systolic and diastolic blood pressures increased significantly in the model group and enalapril group (P＜0.05).
There were no significant differences in the systolic and diastolic blood pressures between the model group and enalapril
group (P＞0.05). After drug intervention, compared with the model group, the systolic and diastolic blood pressures
decreased significantly in enalapril group (P＜0.05). Compared with the control group, the levels of Ang Ⅱ, BUN, CysC and
urinary mALB were significantly increased in the model group (P＜0.05). A large number of blue collagen fibers were
deposited in renal tissue, and the relative mRNA expressions of Ang Ⅱ, TGF-β1, Smad2, Smad3, Collagen Ⅰ and Collagen
Ⅳ were significantly increased (P＜0.05). Compared with the model group, the level of collagen deposition was significantly
reduced in renal tissue, and the above indexes in serum and kidney decreased significantly in enalapril group (P＜0.05).
Conclusion Enalapril has a stable hypertensive effect on SHR, and it can alleviate renal fibrosis and improve renal injury
caused by hypertension by lowering Ang Ⅱ level and inhibiting the expression of TGF-β/Smads signaling pathway.

Key words: Enalapril, rats, inbred SHR, angiotensinⅡ, transforming growth factor beta, renal fibrosis