郑永 黄晨 赵阿丽 王汉民 孙世仁 许国双.含蛋白转导域的SARA/SBD融合蛋白对腹膜透析大鼠[J].现代生物医学进展英文版,2014,14(16):3013-3017. |
含蛋白转导域的SARA/SBD融合蛋白对腹膜透析大鼠 |
Effect of PTD-SARA/SBD Fusion Protein on Peritoneal Morphology andFunction of Peritoneal Dialysis Rats |
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DOI: |
中文关键词: SARA 融合蛋白质类 腹膜 纤维化 |
英文关键词: SARA Fusion proteins Peritoneum Fibrosis |
基金项目:西京医院学科助推计划(XJZT09D06);国家自然科学基金项目(81272621) |
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中文摘要: |
目的:探讨含蛋白转导域的SARA融合蛋白(PTD-SAR/SBD )对腹膜透析大鼠腹膜纤维化的抑制作用。方法:每日腹腔注射
4.25 %葡萄糖腹膜透析液(PDF)制备腹膜透析大鼠模型。28 只Sprague-Dawley大鼠随机分为正常对照组(n=8);腹膜透析模型组
(n=10);PTD-SARA/SBD蛋白干预组(n=10)。4 周后行腹膜平衡试验,检测超滤量、葡萄糖吸收率;留取壁层腹膜组织行HE染色;
免疫组织化学方法检测大鼠壁层腹膜间皮细胞转分化指标E-cadherin 和Twist 的表达;Western blotting 测定E-cadherin、twist,以
及CollagenⅠ、TGF-beta1、P-Smad3、t-Smad3 的表达。结果:①与正常对照组比较,模型组大鼠壁层腹膜增厚,糖转运率增加,超滤量降
低(P<0.01);免疫组织化学与western blotting 检测结果显示E-cadherin 表达下调, Twist表达上调;CollagenⅠ、P-Smad3、TGF-beta1
表达增加。②与模型组比较, PTD-SARA/SBD 蛋白干预组大鼠壁层腹膜糖转运率降低,超滤量增加(P< 0.05);E-cadherin 表达上
调,Twist表达下调;CollagenⅠ、TGF-beta1、P-Smad3 表达减少,各组t-Smad3无明显变化。结论:PTD-SARA/SBD融合蛋白通过抑制
TGF-beta/Smads 信号通路部分逆转腹膜间皮细胞转分化从而改善腹膜结构和功能,为防治腹膜透析所致腹膜纤维化奠定基础。 |
英文摘要: |
Objective: To explore the prevention role of PTD-SARA/SBD fusion protein on peritoneal fibrosis induced by
peritoneal dialysis in rats.Methods:28 male Sprague-Dawley rats were randomly divided into three groups: normal control group(n=8);
peritoneal dialysis model group(n=10); PTD-SARA/SBD group (n=10). The animals were infused by intra-peritoneal injection and were
killed at the end of 4 weeks. A 4 hour peritoneal equilibration test was performed after four-weeks peritoneal dialysis in each group. The
dialysate samples were subjected to determination of 4h ultrafiltration volume (UF) or glucose transporion. The parietal peritoneum
tissues of rats were harvested and stained with H-E for observation of the peritoneal structure. The expression of E-cadherin, Twist,
TGF-beta1, t-Smad3, P-Smad3, and CollagenⅠ in parietal peritoneum was detected with immunohistochemistry or Western blotting assay.Results:Compared with the normal Control group, the UF were lower, and glucose transporion were higher in model group(P<0.01).
The results of western blotting and Immunohistochemistry showed that the level of E-cadherin was down-regulatied, and Twist
expression was up regulation in parietal peritoneum tissues, and TGF-beta1, P-Smad, CollagenⅠ expression increased in the model group;
Administration of PTD-SARA/SBD fusion protein improved the function and structure changes of the peritoneum, improved the level of
E-cadherin and decreased the level of Twist. The expression of TGF-beta1, P-Smad3, CollagenⅠ in parietal peritoneum were decreased in
PTD-SARA/SBD group.Conclusion:PTD-SARA/SBD fusion protein may reverse the epithehal mesenehymal transition by inhibiting
TGF-beta/Smads signaling and improve the peritoneal morphology and function, which lays a foundation of further study on prevention and
treatment of peritoneal fibrosis induced by peritoneal dialysis. |
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