[The improvement effects of Yiqi Huashi Tongluo Formula on oxidative stress and renal fibrosis of experimental CRF rats].

OBJECTIVE

Effects of Yiqi Huashi Tongluo Formula on oxidative stress and renal fibrosis of residual kidney were investigated in five/sixth nephrectomy rats.

METHODS

The rat model of chronic renal failure after nephrectomy was established by Platt method. Two weeks after the operation, the rats were randomly divided into model group, Yiqi Huashi Tongluo Formula (YHT) group, benazepril online (BH) group and sham group, with 8 rats in each group. Treatment was initiated once a day for 12 weeks after successful modeling. Animals were treated once a day with intragastric administration for 12 weeks. (Aqueous solution of free decoction granules in YHT group was 0.276 g/100 g·d. BH group benazepril hydrochloride tablet aqueous solution 0.09 mg/100 g·d gavage; sham group and model group were gavage with 1 ml/100 g normal saline). Urine was collected with a metabolic cage at the end of the 12th week, and urine protein content was detected for 24 hours. The rats were then anesthetized to extract blood from the abdominal aorta and the kidneys. The pathological changes of left kidney were observed by HE staining and Masson staining. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in kidney homogenate were determined by colorimetry. Western blot assay was used to detect the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), kelch-like ech-associated protein-1 (Keap1), NADPH oxidase 4 (Nox4), transforming growth factor-binding 1(TGF-β1), type I collagen (Collagen1) and Nrf2 in the nucleus in renal tissue.

RESULTS

Compared with sham group, model group rats had severe glomerular injury and obvious fibrosis. Levels of Scr, BUN, MDA and 24-hour urine protein excretion, protein expressions of Keap1, Nox4, TGF-β1 and Collagen1 were significantly increased (P＜0.01), while SOD activity and Nrf2 expression were significantly decreased (P＜0.01).Compared with the model group, the degree of glomerular lesion was reduced and fibrosis was less after YHT or BH intervention, and the levels of Scr, BUN, MDA, 24-hour urine protein excretion, protein expressions of Keap1, Nox4, TGF-β1 and Collagen1 were significantly decreased (P＜0.01), while SOD activity and Nrf2 expression were significantly increased (P＜0.01).

CONCLUSION

Through affecting the Nrf2/Keap1 signaling pathway and down-regulating the expression of TGF-β1 protein, Yiqi Huashi Tongluo Formula improved the oxidative stress damage and fibrosis degree of residual kidney in the model rats with renal failure.