Expression alteration of HIF-1α and HSP47 in rats with chronic renal tubulointerstitial fibrosis after irbesartan treatment combined with statin

袁静; 雷泓; 査艳; 杨霞; 沈燕; 胡英; 谢莹; 曾雯

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Expression alteration of HIF-1α and HSP47 in rats with chronic renal tubulointerstitial fibrosis after irbesartan treatment combined with statin

更新时间：2026-01-09

- Expression alteration of HIF-1α and HSP47 in rats with chronic renal tubulointerstitial fibrosis after irbesartan treatment combined with statin
- Journal of Army Medical University Vol. 36, Issue 1, Pages: 42-45(2014)
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  CLC： R-332;R693.2;R972.4
- Published：2014
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袁静,雷泓,査艳,杨霞,沈燕,胡英,谢莹,曾雯.UUO大鼠在厄贝沙坦联合他汀干预下对HIF-1α与HSP47表达的影响[J].陆军军医大学学报(原第三军医大学学报),2014,36(01):42-45.

　Yuan Jing,Lei Hong,Zha Yan,Yang Xia,Shen Yan,Hu Ying,Xie Ying,Zeng Wen.Expression alteration of HIF-1α and HSP47 in rats with chronic renal tubulointerstitial fibrosis after irbesartan treatment combined with statin[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(01):42-45.
袁静,雷泓,査艳,杨霞,沈燕,胡英,谢莹,曾雯.UUO大鼠在厄贝沙坦联合他汀干预下对HIF-1α与HSP47表达的影响[J].陆军军医大学学报(原第三军医大学学报),2014,36(01):42-45. DOI：

　Yuan Jing,Lei Hong,Zha Yan,Yang Xia,Shen Yan,Hu Ying,Xie Ying,Zeng Wen.Expression alteration of HIF-1α and HSP47 in rats with chronic renal tubulointerstitial fibrosis after irbesartan treatment combined with statin[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(01):42-45. DOI：

摘要

目的探讨低氧诱导因子-1α（hypoxia-inducible factor 1α

HIF-1α）及热休克蛋白47（heat shock protein 47

HSP47）在单侧输尿管梗阻（unilateral ureteral obstruction

UUO）大鼠模型中的表达，分析血管紧张素Ⅱ受体拮抗剂厄贝沙坦（Angiotensin Ⅱ receptor blocker

ARB）联合他汀对其表达的影响。方法应用单侧输尿管结扎手术建立UUO大鼠模型，将健康成年的雄性SD大鼠随机分为：模型组（

=10）、假手术组（

=10）、厄贝沙坦60 mg/L组（n=10）、洛伐他汀20 mg/L+厄贝沙坦60 mg/L组（

=10）。术前2 d给药，模型组、假手术组仅予5 mL生理盐水灌胃。观察4组大鼠第2周肾组织病理学改变，应用原位杂交和蛋白印迹检测HIF-1α、HSP47在肾小管间质中的表达。结果 UUO造模后2周与假手术组比较，模型组肾组织有高水平HIF-1α mRNA，并出现HIF-1α蛋白高表达，主要分布在小管间质细胞的细胞质；HIF-1α mRNA的表达与HSP47 mRNA的表达呈正相关（r=0.715，P0.05）。HIF-1α蛋白表达部位及程度与HSP47一致，厄贝沙坦60 mg/L治疗组、洛伐他汀20 mg/L＋厄贝沙坦60 mg/L治疗组大鼠肾小管间质细胞的HIF-1α mRNA和蛋白、HSP47 mRNA表达显著减少（P0.05）。结论厄贝沙坦联合洛伐他汀治疗可能通过降低UUO大鼠HIF-1α与HSP47在肾小管间质中的表达而发挥肾脏保护作用。

Abstract

Objective To determine the expression of hypoxia-inducible factor 1α (HIF-1α) and heat shock protein 47 (HSP47) in rats with chronic kidney fibrosis

and changes of the expression after the treatment of statins and Angiotensin Ⅱ receptor blocker

irbesartan. Methods

A total of 40 healthy adult male rats were divided into 4 groups

that is

unilateral ureteral obstruction group (UUO

=10)

sham operation group (

=10)

lovastatin (20 mg/L) and irbesartan (60 mg/L) intervention group (

=10)

and irbesartan intervention group (

=10). Normal saline and corresponding drugs were given to corresponding rats in 2 d before operation. In 2 weeks after operation

the renal tissues were observed for histopathological changes. In situ hybridization was applied to measure collagen in the kidney

and Western blotting was used to detect the expression of HIF-1α and HSP47 in the renal tubulointerstitium. Results In 2 weeks after UUO operation

HIF-1α mRNA and protein were highly expressed in the cytoplasm of renal interstitial cells in UUO group than in sham operation group. The expression of HIF-1α mRNA was positively correlated with that of HSP47 mRNA (r=0.715

P0.01). Meanwhile

the level of HIF-1α mRNA and protein

and HSP47 mRNA was also down-regulated （

0.05）

especially after union treatment of lovastatin and irbesartan. Conclusion Combined treatment of lovastatin and irbesartan may decrease the expression of HIF-1α and HSP47 in tubulointerstiltium to protect kidney in rat models of developing nephritis.

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