| Objective: Renal interstitial fibrosis is caused by various reasons, renal tubular interstitial diseases of the final result is the development of all chronic kidney disease to end stage renal failure, a common pathway. Renal interstitial fibrosis development is a complex process that involves renal tubular epithelial and interstitial injury, cytokines and inflammatory mediators, inflammatory cell infiltration, fibroblast proliferation, extracellular matrix increase in a series of interrelated process involving the participation of multiple cytokines.Transforming growth factorβ1 (Transforming growth factor TGF-β1) is the most studied and most important factor-induced fibrosis. It can be produced by promoting a large number of matrix elements, as well as chemotaxis and activation of inflammatory cells, mediated by tubular epithelial cells to mesenchymal transdifferentiation, leading to glomerular sclerosis and tubulointerstitial fibrosis, ultimately, to end-stage renal Failure.Thrombospondin 1 (Thrombospondin-1 TSP - 1) as the endogenous angiogenesis inhibitor peptide important one, which can be anti-angiogenesis, which led to renal interstitial fibrosis. In recent years, the study found, TSP-1 can activate endothelial cells to secrete a potential TGF-β, thereby inhibiting endothelial cell growth. TSP-1 as a key body of transforming growth factorβ1 (TGF-β1) activation factor, the important role of kidney disease more and more attention.Vascular endothelial growth factor(Vascular endothelial growth factor VEGF), a nutritional, activation, and promote angiogenesis, the performance of the proliferation of endothelial cells has an indispensable role. In recent years, the study found, VEGF and the relationship between renal interstitial fibrosis is also relatively close. I collagen(type I collagen) is an important renal interstitial fibrosis of extracellular matrix components, I over-expression of collagen is the formation of renal interstitial fibrosis, glomerular sclerosis is an important part of the process. Sirolimus (rapamycin, RAP) is a macrolide produced by Streptococcus immunity against antibiotics, rapamycin is currently mainly used as an immunosuppressant after organ transplantation patients, including renal transplantation. Recent studies have found that rapamycin delayed the progress of CKD may also play a very useful role, it is likely to become the treatment of CKD, the progress of renal dysfunction as a potential drug.The topic to be adopted through the establishment of unilateral ureteral obstruction (unilateral urethral obstruction, UUO)-induced renal interstitial fibrosis, combined with immunohistochemistry and other means of detection, view Chalei Pa ADM on renal interstitial fibrosis organization TSP-1, VEGF, TGF-β1 and expression of collagen type I, and explore rapamycin on renal interstitial fibrosis in rats, prevention and treatment of renal interstitial fibrosis provide theoretical basis for trial.Methods: Select SD rats of clean grade 54 (male), weight (200±20) g, adaptive feeding after 1 week were randomly divided into three groups: control group (A group), UUO model group (model group, B group) and rapamycin treatment group (treatment group, C group), 18 rats in each group. Each group and 3,7,14 days after operation, respectively, were batched out the obstructed kidneys and divided into N3, N7, N14 group, n = 6.The B, C rats to Chloral hydrate (0.1ml/kg) intraperitoneal injection of anesthesia. Under sterile conditions, the back spine on the left side 1.5 cm, ribs 1 cm longitudinal incision line, layer by layer separation along the lower pole of left kidney to find the left ureter, retrograde for the prevention of infection, 1 in the left upper ureter / 3 of the ligation of the upper and lower, respectively, two, and then cut from. A group without ligation, cut ureter, with the former more than the process. Each group at 1 day before surgery administered orally 1 time a day, week, review the weight and adjust the amount of administration. The treatment group rapamycin 2 mg / kg / d orally, the control group and model group were gavaged with isometric saline.Eating free water during the experiment.Each group respectively after 3 days, 7 days, 14 days, 6 rats were randomly selected were remove the obstructed kidney in three batches, placed in fixative, respectively, using hematoxylin eosin (HE) staining, Masson staining The renal pathological changes, and was determined by immunohistochemistry in renal interstitial TSP-1, VEGF, TGF-β1 and collagen type I expression, image analysis system for semi-quantitative analysis.The results are mean±standard deviation (±s), said multi-factor analysis of variance, the application of statistical analysis software SPSS 13.0 for statistical analysis of experimental data, P <0.05 was considered statistically significant.Results: Light microscopy, HE staining no abnormal group A, B group can be seen in the tubules 3 days after mild expansion, renal interstitial infiltrating inflammatory cells seen; dilated renal tubules on day 7, showing renal tubular epithelial cell degeneration, Necrosis, renal interstitial inflammatory cell infiltration, interstitial width was significantly increased; more visible on day 14 of tubular atrophy, diffuse thickening of tubular basement membrane, shrinkage, with varying degrees of fault. A group of no abnormal Masson staining, B group 3 days after surgery shows slight tubular expansion, increased collagen fibers; after 7 days and 14 days, gradually increase the degree of tubular dilatation, collagen fibers increased significantly, interstitial Fibrosis evident. Immunohistochemistry results showed that: TGF-β1 in the A group had no or only trace amounts in renal tubular epithelial cells expressed; in the B group with prolonged obstruction, and its expression progressively increased, with the A group compared with both time points Significant difference (P <0.05); the C group, TGF-β1 expression compared with the same B were decreased (P <0.05), but still higher than A group (P <0.05) expression. TSP-1 was not expressed in the A group; in the B group of widely expressed in renal tubular epithelial cells, and with the obstruction time, the expression increased gradually, with the A group, was statistically significant (P <0.05); In the C group, TSP-1 expression in group B compared with the same period were decreased (P <0.05), but still higher than A group (P <0.05) expression.I collagen expression in the A group, only a smallamount of interstitial and kidney in a large vessel wall; in the B group ofwidely expressed in renal tubular and renal interstitial, and with theobstruction time, the expression increased gradually, with the A groupComparison was statistically significant (P <0.05); I collagen in the expressionof C group during the same period were decreased compared with B group (P<0.05), but still higher than the expression of A group (P <0.05).A group in theperiod of VEGF is widely expressed in glomerular visceral epithelial cells andtubular epithelial cells; in group B on day 3 expression was elevated comparedwith the A group was statistically significant (P <0.05), with Increased renalinterstitial disease, and its expression gradually decreased, the first 14 daysonly a little expression in renal tubular epithelial cells, compared with A, thefirst 7 days, 14 days were lower than the expression of A group (P <0.05); inthe C group, VEGF was expressed after 3 days compared with the same B nosignificant difference compared with the A group has increased significantly(P <0.05), and section 7 Days, the first 14 days the expression of VEGF werehigher than the same period the expression of group B (P <0.05), but werelower than A group (P <0.05).Conclusion: In the unilateral ureteralobstruction in rat renal interstitial TSP-1, TGF-β1 and collagen type Iexpression was significantly increased, and with obstruction of time,increasing the number of its expression, of renal interstitial fibrosis; while theobstruction of VEGF with time, gradually reduce the number of its expression,there renal interstitial fibrosis.Rapamycin inhibits renal fibrosis TSP-1,TGF-β1 and overexpression of collagen type I, and promote the expression ofVEGF, which can improve the morphological changes UUO rat kidneys,reducing tubular dilatation, and reduce tubulointerstitial collagen deposition,delayed renal interstitial fibrosis.
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