| Objective:To study the protective and therapeutic effect of Panax notoginseng saponin (PNS) on renal tubulointerstitial fibrosis in rats with Chronic Renal Ischemia injury induced by renal artery stenosis (RAS) in rats. Chronic renal ischemia is the first signal of the renal interstitial fibrosis. Chronic renal ischemia,as the independent factor, can cause tubu-Lointerstitial injury and renal interstitial fibrosis, that was attracted by more and more people. A large number of studies demonstrated that renal interstitial fibrosis(RIF) is the common pathway that renal disease developed to the end stage renal failure. The degree of the injury in tubule interstitium was correlated with the degree of decline in renal function ,the injury in tubule interstitium play an important factor in the process of renal diseases. So, more and more people attached importance to tubule interstitium.Compared with western medicine, traditional chinese medicine had prioritry in the treatment of cronic disease,so in renal diseases.The effect of traditional chinese medicine and its extract on renal interstitial fibrosis was studied by more people in recent years, Panax notoginseng saponins was the more effective than others. The rats were ligated to establish the model of chronic renal ischemia in this study,PNS was injested to rats to effect renal interstitial fibrosis in rats with chronic renal ischemia,The main purpose of this study aimed to study the protective and therapeutic effect of Panax notoginseng saponin (PNS) on renal interstitial fibrosis in rats with chronic renal ischemia,explore its possible mechanism and provide a theoretical basis for PNS interfering chronic renal ischemia.Methods:Sixty-five sprague-dawley(SD) rats were randomly divided into 3 groups: Sham operation group, Operation group, Panax notoginseng treated group. Renal artery stenosis (RAS) of the rats were ligated to establish the model of chronic renal ischemia. After operation, PNS 50 mg.kg–1.d–1 was injested into the abdomens of the rats in PNS treated group,the same of distilled water as same dose as the PNS was injested into the abdomens of the sham operation group and the operation group.On days 7,14,28 and 45, 5 rats elected in different groups were killed.Hematoxylin and eosin (HE) staining and Masson staining were applied to explore histological and pathological changes in the renal interstitium.Α-smooth muscle actin(Α-SMA) was detected by immunohistochemistry. The concentrations of IL-2 and PDGF in serum were respectively detected by immunofluorescence assay and ELISA method.Results:The degree of tubular damage and renal interstitial fibrosis,the expression ofα-SMA and the levels of serum PDGF-BB in the operated rats were significantly increased as compared with those of the sham operation group(P<0.01) ;The PNS-treated rats had less degree of tubular damage renal interstitial fibrosis at different time points(p<0.05 or p<0.01), less levels of PDGF-BB in serum on days 28,45(P<0.01) and less expression ofα-SMA in interstitium on days 14,28,45 (p<0.05 or p<0.01)than those of the operation group. The IL-2 level of the sham operation group maintained relatively stable throughout the experiment while that of the operation group and the PNS-treated group showed a great increase on day 7(P<0.01) and then decreased to the level of the sham operation group and dropped again on day 45(P<0.05). The level of serum IL-2 of the PNS-treated group was higher than that of the operation group on day 7 (P<0.05),it has not distinction statisticaly at other times. HE staining showed that inflammatory cell infiltration,the renal interstitial edema,the renal tubular expansion and the renal tubular atrophy in PNS treated group were decreased at different time points compared with those in the operation group. Correlation analysis:Correlation analysis was performed between the degree of renal interstitial fibrosis and the expression ofα-SMA, the levels of serum PDGF-BB.There was a significant positive correlation between the collagen deposition measured by Masson Trichrome staining and the expression ofα-SMA, the levels of serum PDGF-BB.Conclusion: Panax notoginseng saponin may prevent fibrotic process of renal interstitium in chronic renal ischemia rat model by blocking tubular epithelial-myofibroblast transdifferentiation, suppressing serum level of PDGF-BB and inhibiting the increasing of the serum IL-2 level in the early stage.
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