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目的探讨粉红胶霉菌对糖尿病大鼠肾组织中转化生长因子β1(TGF-β1)、金属蛋白酶组织抑制剂-1(TIMP-1)、纤溶酶原激活物抑制剂-1(PAI-1)表达水平的调节及其与糖尿病肾脏病变的关系。方法将24只正常雄性Wistar大鼠随机分为空白对照组(N组)8只,糖尿病模型组(M组)8只,粉红胶霉菌治疗组(G组)8只,其中M组、G组应用链尿佐菌素(STZ)6.5mg/100g腹腔注射建立糖尿病大鼠模型。G组成模后给予粉红胶霉菌0.05g/100g.d灌胃,M组与N组给予等量生理盐水灌胃,每4周末监测血糖,8周后观察24h尿蛋白定量及血尿素氮(BUN)、血肌酐(SCr)在血清中的浓度水平,同时行HE、PAS和MASSON染色观察肾脏病理变化,采用实时荧光定量RT-PCR法检测肾脏TGF-β1、TIMP-1及PAI-1mRNA的表达。结果 M组和G组SCr、BUN水平及24h尿蛋白定量明显高于N组(P<0.01),M组上述指标显著升高,与G组比较亦有统计学意义(P<0.01)。肾组织病理学观察N组无明显异常,M组出现肾小球肥大,肾小球内细胞外基质蓄积,基底膜增厚,系膜细胞增生指标明显高于N组(P<0.01),G组病变轻于M组。G组TGF-β1、TIMP-1及PAI-1mRNA的表达均明显低于M组,但高于N组(P<0.01)。结论粉红胶霉菌对STZ诱导的糖尿病大鼠早期肾损伤有一定保护作用及抗肾小球纤维化作用,其机制可能是通过下调TGF-β1、TIMP-1和PAI-1mRNA的表达、减少细胞外基质、减少尿蛋白来实现的。
Objective To investigate the effects of gliadin on the expression of TGF-β1, TIMP-1, PAI-1 in diabetic rat kidney. Regulation of expression and its relationship with diabetic nephropathy. Methods Twenty-four normal male Wistar rats were randomly divided into control group (n = 8), diabetic model group (n = 8) and Gliadin group (n = 8) Diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ) 6.5mg / 100g. Group G was injected with 0.05g / 100g.d of gliadin, and the rats in group M and group N were given the same amount of normal saline. The blood glucose was monitored every 4 weeks. The levels of urinary protein and blood urea nitrogen (BUN) were observed after 8 weeks ), Serum creatinine (SCr) levels in serum were detected by HE staining, PAS staining and MASSON staining. The expression of TGF-β1, TIMP-1 and PAI-1 mRNA in kidneys were detected by real-time fluorescent quantitative RT-PCR . Results The levels of SCr, BUN and 24 h urine protein in group M and group G were significantly higher than those in group N (P <0.01). The above indexes in group M were significantly higher than those in group G (P <0.01). The histopathological observation showed no obvious abnormality in group N, the glomerular hypertrophy in group M, accumulation of extracellular matrix in glomeruli, thickening of basement membrane and mesangial cell proliferation index in group M were significantly higher than those in group N (P <0.01) Group lesions lighter than M group. The expression of TGF-β1, TIMP-1 and PAI-1 mRNA in G group were significantly lower than those in M group, but higher than those in N group (P <0.01). Conclusion Gliadin plays an important protective role in the early stage of renal injury induced by streptozotocin (STZ) -induced diabetic rats and its anti-glomerular fibrosis effect. The mechanism may be that the down-regulation of the expression of TGF-β1, TIMP-1 and PAI- Matrix to reduce urinary protein to achieve.