槌果藤对局灶节段肾小球硬化鼠模型的治疗作用及作用机制的初步探讨

目的：探讨槌果藤对局灶节段肾小球硬化大鼠模型的治疗作用及作用机制。方法：通过左肾切除并阿霉素尾静脉注射的方法建立FSGS模型。按不同灌胃给药浓度将动物分为75g/L组（A组）、150g/L组（B组）、300g/L组（C组）、600g/L组（D组）,另两组分别为安慰剂对照组（E组）和假手术组（F组）。造模后4周给药,疗程4周。各组动物于治疗前后均分别测定24h尿蛋白定量、血常规、肾功能、谷丙转氨酶（ALT）、总蛋白（TP）、白蛋白（Alb）、胆固醇（TC）水平。治疗后取D、E、F组肾组织抽提总RNA,杂交高密度cDNA芯片并分析结果。结果：各槌果藤煎剂组治疗后24h尿蛋白水平均较治疗前显著下降,其中又以D组下降程度最为显著（P〈0.05）。同时各治疗组治疗后血浆白蛋白均较治疗前有显著上升,血胆固醇、肌酐、尿素氮水平均较治疗前有显著降低,而各治疗组治疗前后血红蛋白、白细胞总数、血小板数和谷丙转氨酶水平均无统计学差异（P〉0.05）。基因芯片检测结果显示与E组比较,D组有包括转化生长因子-β1（TGF-β1）、肿瘤坏死因子α（TNF-α）受体、足细胞相关蛋白（Podocin）、纤维连接蛋白等与FSGS发生发展密切相关的基因表达具有统计学差异。结论：本实验中不同浓度的槌果藤煎剂对FSGS大鼠模型均有减少尿蛋白的作用,其中以600g/L组为最强。观察期内各组均未发现骨髓抑制、肝损害等副反应。槌果藤可能通过下调TNF-α受体、EGF受体、TGF-β1、PDGF、纤维连接蛋白、肾特异性膜蛋白、足细胞相关蛋白Podocin以及ILK的基因表达,上调锌指蛋白216以及硒蛋白的表达等起到免疫调节、抗氧化、抗纤维化作用,其确切作用机制需要进一步研究。

Effects and Mechanism of Capparis Spinosa on the Murine with Focal Segmental Glomerulosclerosis

Objective： To determine the effects and mechanisms of Cappris Spinosa on the murine model with focal segrnental glomerulosclerosis （FSGS）. Methods： 60 murine models with FSGS were constructed by adriamycin injection through caudal vein and left nephrectomy. All of the models were divided into 6 groups according to the different concentration of Capparis Spinosa （ 75 g/L Group A, 150 g/L Group B, 300 g/L Group C, 600 g/L Group D）. Group E was placebo control and Group F was sham - operation control. Before and after four weeks treatment, all of the models were taken samples for the detection of renal function, liver function,blood regular test etc. The total RNA of renal tissue of Group D, E, F were contracted and hybrided with cDNA micro- barray. Results：The 24 hours urine protein excretion and blood cholesterol, serum createnine, serum urea of Group A, B, C, D was decreased obviously after treatment （P〈 0.05）. The analyze of microarray indicated that the gene expression as the tissue growth factor β, tumor necrosis factor α receptor, podocin, fibronectin of group D was significantly different with group E, Conclusion： Different concentration of Cappris Spinosa in this research can decrease the urine protein of FSGS murine models, especially group D （600 g/L）. Side- effect had not been detected during the period of observation. Cappris Spinosa might have immune regulation,anti oxidation and anti fibrosis function by down regulate the expression of TNF- α receptor, EGF receptor, TGF- β1, PDGF gene.