川芎嗪对IgA肾病模型大鼠WT1表达的影响

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目的:研究川芎嗪对IgA肾病(IgAN)模型大鼠WT1基因表达的影响及可能的意义。方法:30只清洁级SD雌性大鼠分成正常对照组(A组,8只)、模型组(B组,12只)、川芎嗪组(C组,12只),应用BSA+CCl4+LPS方法造模,直接免疫荧光法检测IgA在肾小球的沉积情况,光镜染色观察肾组织病理改变;电镜观察各组足细胞病理改变;,免疫组化法检测WT1基因在肾脏的表达。结果:①第14、16周末时,C组尿蛋白水平明显低于B组(P<0.01)。②肾组织病理:A组形态无异常,B组大鼠肾小球体积增大,系膜区明显增宽,系膜细胞和系膜基质中度增生为主,肾间质淋巴细胞浸润,肾小球与球囊壁可见粘连,偶见细胞新月体产生,肾小管可见轻度萎缩。C组大鼠肾小球体积均轻度增大,系膜细胞和系膜基质以轻度增生为主,系膜区增宽不明显,少见新月体形成和硬化,肾间质有少数淋巴细胞浸润。电镜下C组足突形态正常,排列整齐。B组多数肾小球足突部分融合;C组足突少部分融合;③WT1免疫组化结果:肾小球内WT1阳性细胞A组(25.38±4.14/肾小球)显著高于B组与C组(均P<0.01);C组(16.38±1.8/肾小球)较B组(12.5±2.45/肾小球)显著升高(P<0.05),WT1在B组肾小管内可见明显表达,C组肾小管内表达较B组减轻,而A组肾小管未见明显表达WT1在M组肾小管内可见明显表达。结论:川芎嗪部分通过保护IgA肾病模型大鼠WT1基因的表达,改善足细胞的功能,进而减轻蛋白尿,而WT1则可能是IgAN肾小管早期损伤敏感的检测指标。 Objective: To investigate the effect of ligustrazine on WT1 gene expression in IgA nephropathy model rats and its possible significance. Methods: Thirty SD female SD rats were divided into normal control group (group A, n = 8), model group (group B, n = 12) and ligustrazine group (group C, n = 12) The immunofluorescence method was used to detect the deposition of IgA in glomerulus. The pathological changes of renal tissues were observed by light microscopy. The pathological changes of podocytes were observed by electron microscope. The expression of WT1 gene in kidney was detected by immunohistochemistry. Results: ① At the end of the 14th and the 16th week, the urinary protein level in group C was significantly lower than that in group B (P <0.01). ②The pathological changes of kidney: no abnormalities were found in group A, the volume of glomeruli in group B was increased, the mesangial area was obviously widened, and the mesangial cells and mesangial matrix were mainly moderately proliferated. The interstitial infiltration of renal interstitium and kidney Globules and balloon wall visible adhesions, occasionally cells crescent, tubular mild shranter. The glomerular volume of rats in group C increased slightly, the mesangial cells and mesangial matrix were mainly mild hyperplasia, the widened mesangial area was not obvious, and the formation and sclerosis of crescent were rare. There were a few lymph nodes in renal interstitium Cell infiltration. Electron microscope group C foot shape normal, arranged neatly. (P <0.05) .WT1 immunohistochemistry results showed that the number of WT1 positive cells in glomerular group A (25.38 ± 4.14 / glomeruli) was significantly higher than that in group B and C (P <0.01). The expression of WT1 was significantly increased in group B (16.38 ± 1.8 / glomeruli) compared with group B (12.5 ± 2.45 / glomeruli) (P <0.05) , And the expression of tubulin in group C was less than that in group B, while the expression of WT1 in group A was not observed in group A and group C (P <0.05). CONCLUSION: Tetramethylpyrazine partly protects the IgA nephropathy model rats from WT1 gene expression, improves podocyte function and then reduces proteinuria, while WT1 may be a sensitive indicator of early renal tubular IgAN injury.
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