肿瘤坏死因子-α增强肾小球前小动脉平滑肌细胞内I型三磷酸肌醇受体的表达

目的 探讨肿瘤坏死因子－α（TNF－α）对肾小球前小动脉平滑肌细胞（RASMC）I型三磷酸肌醇（IP3）受体蛋白表达的影响。方法 通过对RASMC的分离、培养和鉴定,应用蛋白和核酸杂交技术分别检测TNF－α作用后RASMC中I型IP3受体蛋白和I型IP3受体mRAN的表达情况,同时测定I型IP3受体mRNA的半衰期。结果 TNF－α能增强RASMC内I型IP3受体蛋白的表达,且两者呈剂量依赖关系;TNF－α能促进I型IP3受体mRNA的表达,同时使受体蛋白合成增加;而TNF－α对I型IP3受体mRNA的影响不是抑制mRNA的降解,而是使其表达增加。结论 TNF－α可能作用于I型IP3受体mRNA的基因启动子,使其合成增加,由此导致I型IP3受体蛋白表达增加,诱导RASMC内储备的Ca^2 释放至细胞浆,引起肾小球前小动脉平滑肌细胞收缩,使肾血流量减少,肾小球滤过率下降,从而导致肾功能异常。

Tumor necrosis factor-alpha enhances type I inositol 1, 4, 5-triphosphate receptor expression in rat glomerular afferent arterioles smooth muscle cells

OBJECTIVE: To study the effect of tumor necrosis factor-alpha (TNF-alpha) on type I inositol 1, 4, 5-triphosphate receptor (IP(3) R) expression in rat glomerular afferent arterioles smooth muscle cells (RASMC). METHODS: Isolation and culture of RASMC and detection of type I IP(3) R protein and type I IP(3) R mRNA in RASMC after TNF-alpha treatment were carried out with Western blot and Northern blot assay. RESULTS: TNF-alpha enhanced the expression of type I IP(3) R protein and type I IP(3) R mRNA in RASMC; TNF-alpha did not influence the half life of type I IP(3) R mRNA in RASMC treated with TNF-alpha. CONCLUSION: TNF-alpha plays a role in the development of renal dysfunction. The mechanisms may be that TNF-alpha takes part in the change of signal transduction in RASMC. TNF-alpha may act on the promoter of type I IP(3) R mRNA in RASMC and results in the expression of type I IP(3) R protein that stimulates release of intracellular Ca(2+) in RASMC and induces contraction of RASMC. The renal blood flow diminution leads to the development of renal dysfunction.