ABSTRACT
Objective To observe the influence of Yishen Huoxue prescription on expressions of vascular endothelial growth factor-2 (VEGF-2) and Notch4 in rats with unilateral ureter obstruction (UUO).Methods Ninety-six male Sprague-Dawley (SD) rats were randomly divided into sham operation group, UUO model group, losartan group, and Yishen Huoxue group, with 24 rats in each group. The rat models of renal fibrosis were reproduced by using UUO method, and they were treated by Yishen Huoxue herb prescription or losartan intra-gastric administration respectively for therapeutic interference. In the sham operation group, simply the unilateral ureter was separated from the near-by tissues and then the abdomen incision was stitched. The blood was collected on 7, 14 and 21 days after operation for determination of blood urea nitrogen (BUN) and serum creatinine (SCr). Kidney tissues specimens were harvested, and microvessed desity (MVD), the protein expression levels of VEGF-2 and Notch4 in the kidney were detected. Results Compared with UUO model group, BUN and SCr in both treatment groups were significantly decreased with significant difference (allP 0.05). The expression levels of VEGF-2 and Notch4 in sham operation group at each time point were in normal range; with the time extension, the expressions of VEGF-2 and Notch 4 protein were slightly increased, and the descent degree of MVD in kidney was aggravated gradually in UUO model group. The VEGF-2 and Notch4 protein expressions in kidney tissues of the two treatment groups were significantly increased compared with those in model group, the expression of VEGF-2 (A value) reached the highest level on the 14th day after operation (VEGF-2 levels in sham operation, model, Yishen Huoxue Herb prescription and losartan groups were 0.18±0.09, 4.73±0.72, 7.27±1.35, 8.11±1.64 on the 14th day, and they were 0.19±0.07, 4.05±0.88, 7.10±1.12,7.79±1.53 on 21th day, respectively), later representing a tendency of slight decrease, and Notch4 protein expression (A value) peaked on the 21st day (0.62±0.35, 9.08±1.52, 14.48±3.14, 15.54±3.38 in above four groups, allP < 0.05). The degrees of decrease in renal MVD (microvessel/mm2) in the both treament groups was significantly less than that in model group (45.20±6.25, 25.34±4.67, 30.23±4.20, 32.26±4.36 on the 7th day, 46.07±6.22, 20.06±3.98, 26.88±4.36, 26.95±4.11 on the 14th day, 45.18±6.10, 17.79±3.72, 21.71±4.25, 21.68±4.41 on the 21st day in above four groups,P < 0.05 orP < 0.01). There were no statistically significant differences in the above values between Yishen Huoxue herb group and losartan group.Conclusion Traditional Chinese medicine benefiting qi for activating blood circulation therapy (Yishen Huoxue herb prescription) has obvious improving effect on the microvascular injury in the process of renal fibrosis that possibly is related closely to the drug regulation on VEGF/Notch signaling cascade.