Expression of connective tissue growth factor following Sodium Ferulate in rats with unilateral ureteral obstruction / 中国组织工程研究

ABSTRACT

BACKGROUND: Connective tissue growth factor (CTGF) is a kind of factor that can mediate downstream action of transforming growth factor-β 1 (TGF- β 1). The upregulation of connective tissue growth factor expression plays an important role in pathological changes of renal interstitial fibrosis.OBJECTIVE: To explore the effect of Sodium Ferulate on the expression of CTGF mRNA and protein in rats with unilateral ureteral obstruction (UUO) and pathological changes of renal interstitial fibrosis, and to compare with Losartan.DESIGN: Randomized and controlled animal trial.SETTING: Department of Nephrology, West China Hospital of Sichuan University, and College of Public Health, Sichuan University.MATERIALS Twenty-four healthy adult male SD rats were selected from the Experimental Animal Center of Sichuan University. Sodium Ferulate was provided by Sichuan Hengda Pharmacy Co, Ltd (No. 050302); rabbit anti-rat CTGF by Santa Cruz; Western blotting by BioRAD, USA; DNA Engine OpticonTM real-time fluorescent quantitation PCR device by MJ Research, USA.METHODS: The experiment was performed at Research Laboratory of Clinical Medicine (grade BSL-1), College of Public Health, Sichuan University from May to December 2006. Twenty-four healthy rats were randomly divided into 4 groups (n=6) UUO model group, Sodium Ferulate group, Losartan group, and sham-operation group. According to the previous protocol, UUO models were established in UUO model group, Sodium Ferulate group, and Losartan group, and the other rats were subjected to sham operation. From the first day after UUO, Sodium Ferulate group was intragastrically (i.g.)administrated with 150 mg/kg/d Sodium Ferulate; Losartan group was administrated ig. with 20 mg/kg/d. Losartan; UUO and sham operation groups were administrated i.g. with matching normal saline. All rats were executed 14 days after UUO to harvest partial renal tissues. All experimental procedure was accorded with animal ethical standards.MAIN OUTCOME MEASURES: The mRNA and protein expressions of CTGF were quantified by real-time PCR and Western blot. The pathological changes of renal interstitial tissues were observed by hematoxylin/eosin (HE) and Masson staining.RESULTS: Twenty-four rats were included in final analysis. Fourteen days after UUO, CTGF mRNA and protein expressions in UUO model group were significantly increased compared with sham operation group, but the expressions in Sodium Ferulate group were significantly lower than model group (P < 0.05). Compared with Losartan treated group, there was no significant difference (P > 0.05). HE and Masson staining showed inflammatory cell infiltration and tubular and interstitial changes as well as collagen deposition in renal interstitial tissues on day 14 after UUO. Sodium Ferulate obviously improved the renal pathological changes in UUO rats (P < 0.05), and the effect was similar to Losartan (P > 0.05).CONCLUSION: Sodium Ferulate inhibits UUO-induced renal interstitial fibrosis. This action, similar to the effect of Losartan, might be due to downregulation of CTGF expression.