| Background:Ischemic nephropathy induced by atherosclerotirenal arterial stenosis (ARAS) is an important cause of end stage renal failure. The key reason of the progression of ARAS is "hypoxia-microvascular abandoned-tubule-interstitial fibrosis". The progress is the main mechanism of the associated with atherosclerosis, the microvascular endothelial damage process waste-hypoxia caused by tubular interstitial fibrosis.Current drug optimization (Optimal medicine treatment, OMT) treatment is not able to completely prevent the occurrence of ESRD patients, and vascular remodeling did not show the advantage of OMT, so to explore Chinese medicine treatment of ARAS has important practical significance. We always studied its pathogenesis, syndrome of traditional Chinese medicine, and clinical choice for reasons the kidney qi and dispelling the lishi slow decaying treatment ARAS, preliminary clinical trials show that the party can delay the progress of ARAS patients renal function.This study is based on with past clinical work to carry out the deep research of traditional Chinese medicine treatment of ARAS.Objection:This study observatied the influence of the Huanshuai oral liquid on atherosclerotic renal artery stenosis (ARAS) in mice kidney on the expression of hypoxia-inducible factor (HIF-la) and tubular epithelial cell growth factor (TGF-β) by the light microscope, immunohistochemistry and RT-PCR technique which was from genetic to organization,then to explor the influence of the mechanism of the Huanshuai oral liquid on hypoxia-microvascular waste-renal interstitial fibrosis in ARAS.Methods: The ARAS mice model was established by high fat feed and uninephrectomy in internationally recognized model of atherosclerosis-apolipoprotein E gene defects (ApoE-/-) mice.The Left nephrectomies ApoE-/-mice were divided into TCM group(Huanshuai recipe oral liquid), western medicine group, model group, and normal control group (the wild type mice (C57BL/6j). Two weeks after the abolition, all mice were given medicine for12weeks.Renal function,blood fat,Atherosclerosis and renal interstitial fibrosis were assessed at12weeks after taken medicine via HE,Masson to observe the stenosis of the renal artery,the immunohistochemical method to detect the expression of the Ⅳ collagen type,alpha smooth muscle actin (a-SMA)andⅧ factor related antigen (vWF),and RT-PCR to detect the expression of hypoxia-inducible factor (HIF-1a) and transforming growth factor (TGF-β),then.Western-blot technique to observe the expression of vascular endothelial growth factor (VEGF).Conclusion:1.The influence of Huanshuai recipe oral liquid on renal function and blood lipids:(1)Serum creatinine and urea nitrogen:The difference between model group and wild group was statistically significant (P<0.05),this means model group mice’s renal function significantly lower than normal mice.The western medicine group compared with model group (P<0.05), suggesting that after treatment of western medicine, western medicine group experienced renal function improved significantly, the western medicine treatment is effective.The difference between Chinese traditional medicine group and model group was statistically significant (P <0.05), suggesting after the traditional Chinese medicine therapy, Chinese medicine group experienced renal function improved significantly, traditional Chinese medicine treatment is effective.Compared the traditional Chinese medicine to the western medicine group there was no statistically significant difference (P>0.05), showing that in this experiment, the two groups in reducing the serum creatinine and urea nitrogen were no significant difference.(2)Triglyceride and total cholesterol:The difference about serum TG, CHO between model group and wild mice was statistically significant (P<0.05), the model group mice serum TG, CHO obviously higher than normal mice.The difference about serum TG, CHO between Traditional Chinese medicine group and model group mice was statistically significant (P<0.05), Chinese medicine treatment can obviously reduce the mice serum TG and CHO.The difference about serum TG, CHO between western medicine group and model group was no statistically significant (P>0.05).2.The influence of Huanshuai recipe oral liquid on the renal artery andkidney tissues:(1)Renal artery:The model group renal artery stenosis was significant under microscopical observation, and there were a large number of foam cells in subcutaneous, patch up fiber and fiber cap.The stenosis of Chinese traditional medicine group renal artery was significantly reduce.The statistics analysis:The difference between the model group and wild statistically significant (P<0.05).The difference between the Traditional Chinese medicine (TCM) and the model group was statistically significant (P<0.05),and the difference between the western medicine and the model group was statistically significant (P<0.05), that is to say, Chinese and western medicine can both reduce the damage of renal artery.the difference between the Traditional Chinese medicine and western medicine group was statistically significant (P<0.05), indicated that taking herbal medicine to improve renal artery damage is superior to western medicine.(2)Kidney tissues:Masson staining:The wild group of renal interstitial renal tubular has no atrophy and interstitial fibrosis, no inflammatory cell invasion.The model group renal interstitial fibrosis is obvious and great quantities inflammatory cells distributed in renal interstitial.Western medicine group of renal interstitial has more inflammatory cells than the wild group, renal tubule and interstitial damage is not obvious.The renal interstitial of Chinese traditional medicine group shew a small amount of inflammatory cells,and the kidney damage is not obvious.3.The detection of HIF-1α and TGF-β by RT-PCR Compared with the wild in the control group,The expression of HIF-1α and TGF-β of the model group was significantly higher (P<0.05).The Chinese traditional medicine group compared with model group, The expression of HIF-1α and TGF-β decreased (P<0.05).Immunohistochemical to detecte IV collagen,alpha smooth muscle actin (alpha SMA), and vWF:The Chinese traditional medicine group compared with the model group, the expression of collagen type IV and alpha SMA, vWF were increased,and the difference was statistical significance (P<0.05).Western blot to observe the expression of VEGF in the kidney tissue:VEGF expression compared "with the wild group,the model group decreased significantly (P<0.05);Compared the model group with the Chinese traditional medicine group, VEGF decreased (P<0.05);Compared the Traditional Chinese medicine with the western medicine group, there was no significant differences.Conclusion:1.Huanshuai recipe oral liquid can obviously improve the renal function of the ApoE-/-mice,and decrease serum creatinine,urea nitrogen,the serum triglyceride and total cholesterol.2.Huanshuai recipe oral liquid can significantly improve renal artery stenosis.3.Huanshuai recipe oral liquid can obviously desease the level of the fibrosis factors,such as TGF-beta, alpha SMA, collagen type Ⅳ, HIF-1alpha,and at the other hand,can raise the level of VEGF, and inhibit the capillaries wasting. |
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