| Objective:By observing the tanshinone type ⅡA sulfonate red cell membrane of adriamycin nephrosis rats,24h urine protein quantitative detection, biochemical indexes such as plasma albumin, low density lipoprotein cholesterol triglycerides,creatinine; Whole blood viscosity, plasma viscosity was showed to learn index; The red cell membrane sial ic acid content, MDA content, kidney pathological way form; Kidney Col-Ⅳ, FN, TGF-β1, PAI-1 protein expressio; Kidney tissues, MMP-9 and TIMP-1、PAI-1, TGF-β1 mRNA expression, and to explore its mechanism.Methods:Spyware doctor 80 male rats were randomly divided into blank group, model group, positive control group, tanshinone Ⅱ A low dose group, tanshinone Ⅱ A high dose group. With adriamycin one-time tail intravenous dose of 6.5mg/kg, copy adriamycin nephrosis model, building 21 days after each dose group were given corresponding dose of intraperitoneal injection of drugs. Positive medicine control group (reduced glutathione for injection 170mg/kg/d-1). Tanshinone Ⅱ A high dose group (7mg/kg/d-1), low dose group (3.5mg/kg/d-1) intraperitoneal injection, the model group with distilled water, each group respectively for 2 weeks.24h urine protein quantitative detection, biochemical indexes such as plasma albumin, low density lipoprotein cholesterol (ldl-c), triglycerides, creatinine.Whole blood viscosity, plasma viscosity was showed to learn index; The red cell membrane sialic acid content, MDA content, kidney pathological way form. By observing immune histochemical method kidney Col-Ⅳ, FN, TGF-β1, the influence of PAI-1 protein expression; The PCR method is adopted to observe nephropathy rat kidney tissues, the influence of MMP-9 and TIMP-1、PAI-1、TGF-β1 mRNA expression.Results:1. Tanshinone type ⅡA sulfonate can reduce adriamycin nephrosi s rats plasma vi scosi ty, whole blood viscosity, sialicacid content, MDA content, compared with model control group with significant difference (P<0.05). Whole blood viscosity and plasma viscosity in blank group rats and compared, whole blood viscosity in the 30s-1,60s-1 under the shear rate and the model group were significantly lower (P<0.05), tanshinone Ⅱ A sulfonate whole blood viscosity in treatment group compared with model group significantly reduced, including tanshinone Ⅱ A low dose group is close to blank.2. The building between groups of rats after 24 h urine protein quantitative increases, reduced plasma albumin in model group, low density lipoprotein cholesterol (hdl-c), elevated triglycerides, creatinine and urea nitrogen. Tanshinone Ⅱ A treatment group of 24 h urine protein quantitative detection has decreased, compared with model group, positive control group (P<0.05); Tanshinone type IIA sulfonate can reduce the red cell membrane adriamycin nephrosis rats MDA content.3. Each group in the rat kidney pathological changes: the blank group:glomerular morphology neat, did not see cystic cavity expansion, renal tubular epithelial cell cytoplasm nucleus is normal. Did not see interstitial inflammatory cells, blood cells glomerular exist. Glomerular capillary loops and opening is good, the foot process form is normal, no fusion, sertoli cell degeneration, mesangial cells and matrix hyperplasia, mesangial area without electron dense deposit. Model group:mesangial area have fog immune complex deposition, microvilli degeneration, such as mitochondria vacuoles degeneration, lysosome increased, podocyte foot process fusion, open bad glomerular capillary loops, renal tubular change is not obvious, not complete mitochondrial membrane, glycogen particles. Positive medicine control group:foot process fusion, segmental fusion, vascular cavity expansion is bad, podocyte foot process fusion, microvilli degeneration, such as mitochondria vacuoles degeneration. High dose groups:light foot process change compared with model group (segmental fusion or a small amount of fusion), a small amount of mist immune complex mesangial area. Tubular epithelial hyperplasia of lysosomes, high tubular mitochondria is normal. No obvious broadening mesangial area, glomerular capillary loops better open, no thickening of glomerular basement membrane, no microvilli degeneration, sertoli cell ultrastructure has no obvious change. Low dose group:capillary loops expansion is good, the foot process segmental fusion, mesangial area did not see the immune complex deposition, mitochondrial proliferation. Mesangial area without apparent broadening or broadening, glomerular capillary loops well open, part of the glomerular capillary loops slightly narrow, no obvious thickening of glomerular basement membrane.4. Tanshinone type ⅡA sulfonate can reduce adriamycin nephrosis rats kidney tissues to decide TGF-β1, PAI-1 protein expression, compared with model control group with significant difference (P<0.05). At the same time, tanshinone type ⅡA sulfonate increase adriamycin nephrosis rats kidney MMP-9 gene expression, reduce the expression of PAI-1mRNA and TIMP-1mRNA in the kidney, the difference was statistically significant compared with model group (P<0.05).Conclusion:Tanshinone type ⅡA sulfonate on adriamycin nephropathy may be through the increase the red cell membrane deformation, reduce blood viscosity, reduce the MDA and antioxidant effect into full play. Tanshinone type IIA sulfonate adriamycin nephrosis is probably by reducing the 24 h urine protein quantitatively, the improvement of pathological tissue damage, reduce the adriamycin nephrosis rats kidney Col-Ⅳ、FN、TGF-β1, PAI-1 protein expression, increase MMP-9mRNA, decline TIMP-1mRNA and PAI-1mRNA expression in the kidney from its intervention may be one of the mechanism of action of Minimal change nephropathy to the progress of glomerular sclerosis. |
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