| Objective:To investigate the effects of dual blockage of rennin-angiotensin system (RAS) for Shh and Ptchl protein expression of the Shh pathway family members and its target gene VEGF on renal in experimental diabetes nephropathy rats, to investigate the role of Shh pathway in the pathogenesis of diabetes nephropathy. Methods:Using renal specimens (paraffin embedded tissue) from successful established modeling of SD rat with experimental diabetes nephropathy (DN) through injected low dose streptozotocin and fed with high fat and sucrose diets to male SD rats. Then, the rats were divided into five groups, the normal control group (group A), simple diabetic nephropathy model rats (group B), DN rats were treated with benazepril (10 mg·kg-1·d-1×8 weeks intragastrically) (group C) or irbesartan (30 mg·kg-1·d-1×8 weeks, intragastrically) (group D) or benazepril combined irbesartan (the dosage of drugs used as mentioned above) (group E). Then all rats were killed after 8 weeks and renal tissues were embedded in paraffin. The Image Pro Plus 6.0 (IPP) image analysis system was used for determined the expression of proteins based on immunohistochemical stained color. The data of parameters was analyzed by SPSS 18.0 analysis software. The quantitative data were expressed as the mean ± standard deviation (x±s). One-way ANOVA test was used for comparison of prameters between groups of rats. The correlation between protein expression of components was analyzed by the Spearman rank correlation analysis, and P<0.05 for the difference was considered as statistically significant. Results:Ptchl and Shh proteins were mainly expressed in rat renal tubular epithelial cells, VEGF protein was existed in glomerular endothelial cells and renal tubular epithelial cells. (1) The protein expression levels of Shh and Ptchl in renal tissue of group A, C, D and E group were significantly higher than group B (P<0.05). Compared with the group A, the expression of Shh, Ptchl in group C, D and E were increased (P<0.05), respectively. Compared with the group C and group D, the expression levels of Shh and Ptchl protien were elevated in group E (P<0.05). But it was not found significantly difference between the expression levels of above molecules in group C and D (P>0.05). (2) The expression level of VEGF protein in kidney tissue of group B was significantly higher than group A (P<0.01). Compared with the group B, the expression of VEGF in group C, D and E were decreased profoundly (P<0.05), respectively. Compared with the group C and group D, the VEGF expression level was decreased obviously in group E (P<0.05), respectively. However, it was not showed that significantly difference between the group C and D (P>0.05). Conclusions:It is demonstrated that ACEI and ARB drugs can significantly reduce the expression of VEGF protein throuth blocking the renin-angiotensin system, and increase the expression of Shh and Ptchl protiens in renal tissue of diabetes nephropathy. The abnormal activation of Shh signaling pathway might be involved in pathophysiological mechanism of diabetic nephropat-hy. |
PDF Full Text Request