雷公藤甲素对5/6肾切除大鼠uPAR和β3整合素表达的影响

Effects of triptolide on expression of uPAR and integrin β3 in focal segmental glomerulosclerosis rats

目的:观察雷公藤甲素对局灶节段硬化性肾小球肾炎(FSGS)大鼠血清及肾组织尿激酶型纤溶酶原激活物受体(u PAR)和β3整合素的影响。方法:取健康清洁级雄性SD大鼠随机分为对照组,FSGS模型组,雷公藤甲素低、中、高剂量组。通过行5/6肾切除术建立FSGS大鼠模型。雷公藤甲素低、中、高剂量组从术后第8天开始定时灌胃治疗,给药10周。检测大鼠第4、8、12周24h尿蛋白水平,肾组织病理,血清及肾组织中的u PAR和β3整合素表达。结果:模型组及各给药组24h尿蛋白定量高于正常组同期(P<0.01),与模型组同期比较,雷公藤甲素中剂量组大鼠24h尿蛋白定量在第12周时明显减少(P<0.01),雷公藤甲素高剂量组大鼠24h尿蛋白定量从第8周开始明显减少(P<0.01)。与雷公藤甲素低剂量组比较,雷公藤甲素高剂量组大鼠24h尿蛋白定量第8周时明显减少(P<0.05)。肾脏病理提示模型组可见不同程度肾小球硬化,系膜细胞及基质中度至重度增生,小管上皮细胞损伤,间质萎缩并可见不同程度纤维化,经雷公藤甲素干预后,肾小球硬化程度明显减轻。u PAR和β3整合素在正常大鼠肾组织及血清中只有少量表达,与正常组比较,在模型组肾组织及血清中表达较强(P<0.01),各治疗组治疗后,表达较模型组明显下降,其中雷公藤素高剂量组差异有统计学意义(P<0.01)。结论:雷公藤甲素能减少尿蛋白,改善肾小球硬化、球囊粘连及系膜基质增生的情况,下调血清及肾组织中的u PAR和β3整合素的表达,延缓肾脏病变程度。

Objective: To observe the effects of triptolide on the expressions of u PAR and integrin β3 in the kidney of rats with focal segmental glomerulosclerosis(FSGS). Methods: Male SD rats were randomized to normal group, model group, the low dose group of triptolide, the middle dose group of triptolide and the high dose group of triptolide. It began eight days after modeling, triptolide low, medium and high dose groups were quantitative feed the drug by gastric perfusion at regular time. The rats were examined 24 hours' urinary protein, pathological change of renal tissue and the expression of u PAR and integrin β3 in blood serum and renal tissue. Results: Compared with the normal group, operation group rats' 24 h urinary protein have increasedsignificantly(P<0.01). Compared with the model group, in twelve weeks the middle dose grop rats' 24 h urinary protein have decreased(P<0.01), while from the eighth week the high dose group has decreased significantly(P<0.01). From eighth week, compared with the little dose group group, high dose group rats' 24 h urinary protein have decreased significantly(P<0.05). Renal pathology prompted varying degrees of glomerular sclerosis, moderate to severe hyperplasia of mesangial cells and matrix, tubular epithelial cells injury and interstitial atrophy with varying degrees of fibrosis in model group, after the treatment of triptolide, renal fibrosis was reduced obviously. u PAR and integrin β3 expressed little in normal kidney tissue and blood serum, highly expressed in model renal tissue and blood serum(P<0.01), compared with the model group, the expression of it was decreased in treatment groups, which was statistically significant in the high dose group(P<0.01). Conclusion: Triptolide can reduce urinary protein,improve the development of glomerular sclerosis and delay end-stage renal failure from happening. Triptolide can inhibit the expression levels of u PAR and integrin β3 in FSGS rats.