Expression of HIF-1alpha in 5/6-nephrectomized rat models of chronic kidney fibrosis.
- Author:
Hui XU
1
;
Xing LIU
;
Wangbin NING
;
Lijian TAO
Author Information
1. Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Connective Tissue Growth Factor;
genetics;
metabolism;
Fibrosis;
metabolism;
Hypoxia-Inducible Factor 1, alpha Subunit;
genetics;
metabolism;
Kidney;
pathology;
Kidney Diseases;
drug therapy;
etiology;
metabolism;
Male;
Nephrectomy;
Perindopril;
pharmacology;
therapeutic use;
RNA, Messenger;
genetics;
metabolism;
Random Allocation;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Central South University(Medical Sciences)
2009;34(4):308-312
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To determine the expression and effect of hypoxia-inducible factor 1alpha (HIF-1alpha) in chronic kidney fibrosis, and to observe the effect of perindopril on its expression.
METHODS:The rat models of chronic kidney fibrosis were induced by 5/6 nephrectomy, and 11 successful 5/6-nephrectomized rats were randomly assigned to 2 groups: a surgery group (n=6) and a treatment group (perindopril, n=5). A control group was induced by sham operation. Five weeks later, Picro-Sirius red stained was applied to measure collagen in the kidney, and Western blot was used to test HIF-1alpha protein; The expression of HIF-1alpha and CTGF mRNA in the kidney was analyzed by real-time PCR.
RESULTS:Picro-Sirius red stained revealed significant accumulation of collagens in the surgery group than the control group; and lower accumulation of collagens in the treatment group than the surgery group. Western blot showed higher deposit HIF-1alpha in the surgery group than the control group (P<0.01) and lower deposit HIF-1alpha in the treatment group than the surgery group (P<0.01). Real time PCR showed higher expression of HIF-1alpha and CTGF mRNA in the surgery group than the control group (P<0.01)and lower expression of HIF-1alpha and CTGF mRNA in kidney of the treatment group compared with the surgery group (P<0.01). The expression of CTGF had positive correlation with HIF-1alpha (r=0.68, P<0.01).
CONCLUSION:The HIF-1alpha may induce kidney fibrosis through CTGF. Perindopril may decrease the expression of HIF-1alpha and CTGF to ameliorate kidney fibrosis.