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机构地区:[1]哈尔滨医科大学附属第一医院肾内一科,150001
出 处:《临床肾脏病杂志》2011年第1期38-40,共3页Journal Of Clinical Nephrology
基 金:省科技厅重点攻关项目(GC07C35301);黑龙江省教委基金(11511187)
摘 要:目的应用氯沙坦对大鼠IgA肾病模型进行干预,观察其对IgA肾病小管间质损害的影响。方法采用牛血清白蛋白(BSA)+脂多糖(LPS)+四氯化碳(CCl4)方法建立IgA肾病大鼠模型,设立正常对照组(A组)、IgA模型组(B组)、氯沙坦治疗组(C组),每组6只,实验前后进行相关生化指标的测定,光学显微镜观察肾脏的组织形态学改变;免疫组织化学法观察各组转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α—SMA)表达;逆转录聚合酶链(RT-PCR)方法检测TGF-β1、单核细胞趋化蛋白1(MCP-1)变化。结果B组尿蛋白量增高,C组则有所降低(P〈0.05);实验前、后,B组肾功能改变显著,C组变化无统计学意义(P〉0.05);B组大鼠肾脏组织中存在不同程度的系膜细胞增生,肾小管上皮细胞肿胀、空泡变及间质炎细胞浸润,而C组上述变化减轻;免疫组织化学法及RTPCR检测显示TGF-β1、α-SMA及MCP-1在A组肾小管及间质中微量表达,B组高表达,C组表达减少。结论IgA肾病存在肾小管间质的损伤;氯沙坦减少IgA肾病大鼠尿蛋白的排泄,抑制炎症及纤维化因子的表达,对IgA肾病小管间质的损伤起保护作用。Objective To observe the effects of losartan on on tubulo-interstitial injury in the rat model of IgA nephropathy. Methods Experimental rat models of IgA nephropathy was induced by using bovine serum albumin, lipopolysaccharide and carbon tetrachloride. SD rats were randomly divided into control group (n = 6), IgA model group (n = 6) and losartan group (n = 6). The related biochemical indicators were determined before and after the experiment. The morphologic changes of renal tissues were observed under the electron microscopy. Immunohistochemistry was used to detect the expression of transforming growth factorβ1 (TGF-β1) and a-smooth musle actin (α-SMA), and reverse transcription-polymerase chain reaction (RT-PCR) to detect the expression of TGF-β1 and monocyte chemoattractant protein-1 (MCP-1). Results As compared with control group (2. 82 ± 0. 34), 24-h proteinuria was increased markedly in IgA model group ( 14. 14 ±1.99), but significantly reduced in losartan group (1.59 ±0. 18). In IgA model group, the changes of renal function were significant, but in losartant group there were no significant difference. There was mesangial proliferation to varying degrees, swollen renal tubular epithelial cells, vacuolar degeneration and infiltration of inflammatory cells in renal tissues of IgA model group, but the tubulo-interstitial injury was notably alleviated in losartant group. Immunohistoehemistry and RT-PCR revealed that TGF-β1, α-SMA and MCP-1 had weak expression in tubule and interstitiurn in control group, high expression in model group, and reduced expression in losartan group. Conclusions There exists tubulo-interstitial injury in IgA nephropathy. Losartan decreases urine protein excretion of the rats and suppresses the expression of inflammation and fibrosis factors to protect the tubulo-interstitial injury in IgA nephropathy.
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