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Reno-protective effects of Ligustrazine and its action on expression of hypoxia-inducible factor-1α in rats with unilateral ureteral obstruction

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Author:
No author available
Journal Title:
Chinese Journal of Biomedical Engineering
Issue:
3
DOI:
10.3760/cma.j.issn.1674-1927.2015.03.003
Key Word:
川芎嗪;输尿管梗阻;缺氧诱导因子1,α亚基;肾;Ligustrazine;Ureteral obstruction;Hypoxia-inducible factor 1,α subunit;kidney

Abstract: Objective To investigate the reno-protective effects of Ligustrazine and its action on expression of hypoxia-inducible factor-1 α (HIF-1 α) in rats with unilateral ureteral obstruction.Methods Sixty healthy,6-week-old male SD rats were randomly divided into the treatment group,model group,and sham operation group (n=20 each).The treatment group was processed with modeling of unilateral ureteral obstruction,and was given the Ligustrazine by injection;the model group was processed with modeling alone,and was given the same dose of normal saline by infusion;the sham operation group only underwent surgical isolation of ureter,without ligation.At 7 and 14 d after the operation,10 rats in each group were randomly selected to be determined for serum creatinine,urea nitrogen,and urine β2-microglobulin.At 7 and 14 d after the operation,10 rats in each group were executed.The rats in model group and the treatment group were harvested for the kidneys on the obstructed side,and those in sham operation group were harvested for the kidneys on the operated side.The harvested kidneys were subjected to pathomorphological analysis.The expression of HIF-1α in renal tissues was determined by immunohistochemistry and Western blotting.Results After the Ligustrazine treatment at 7 d,there were no statistically significant differences in the serum creatinine,urea nitrogen,and urinary β2-microglobulin content of rats between the model group and the treatment group,but these were higher compared with those in the sham operation group (all P<0.05).After the Ligustrazine treatment at 14 d,the serum creatinine,urea nitrogen and urinary β2-microglobulin content of rats continued to be higher in the model group and the treatment group compared with those in the sham operation group (all P<0.05),but these levels were significantly lower in the treatment group compared with those in the model group (all P<0.05).After the Ligustrazine treatment at 7 and 14 d,no significant pathological changes,degeneration of epithelial cells,and interstitial inflammatory cells were found in the kidneys of the sham operation group.After the Ligustrazine treatment in the model group,renal tubular ectasia,lymphocyte infiltration,and hyperplasia of fibrous tissues were found at 7 d,and renal tubular epithelial cell atrophy or necrosis,lumen ectasia,massive lymphocyte and mononuclear macrophage infiltration,and significant hyperplasia of fibrous tissues were found at 14 d in renal interstitium.After the Ligustrazine treatment in the treatment group at 7 d,lymphocyte infiltration,hyperplasia of fibrous tissues,and focal bleeding were found.After the Ligustrazine treatment in the treatment group at 14 d,hyperplasia of interstitial fibrous tissues and inflammatory cell infiltration were significantly improved and the interstitial bleeding lesions were decreased,compared with those in the treatment group at 7 d and the model group at 7 and 14 d.The expression of HIF-1α in renal tissues of rats in the model group and the treatment group after the Ligustrazine treatment at 7 d and 14 d was significantly increased compared with that in the sham operation group.There was no statistically significant difference in the HIF-1 αt expression in renal tissues of rats between the treatment group and the model group after the Ligustrazine treatment at 7 d,whereas the HIF-1 α expression in the treatment group was significantly decreased compared with that in the model group at 14 d (immunohistochemistry 7 d:11.12±3.10,19.70±4.10 vs 2.66±0.88,14 d:7.64±3.11 vs 35.44±5.01 vs 2.82±0.73;Western blotting 7 d:13.12±3.23,20.70±3.14 vs 2.82±1.18,14 d:7.66±3.67 vs 31.41±2.11 vs 2.52±0.13;all P<0.05).Conclusion Ligustrazine can improve the renal function in rats with unilateral ureteral obstruction,and down-regulate the expression of renal HIF-1α,which can be used as an adjuvant therapy for obstructive nephropathy.

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