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目的:通过双环醇干预单侧输尿管梗阻(uniliteral ureteral obstruction,UUO)模型大鼠,动态观察核转录因子-κB(nuclear factor-κB,NF-κB)、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1,PAI-1)和PAI-1 mRNA在梗阻侧肾组织间质中的表达,探讨双环醇延缓肾间质纤维化的可能机制。方法:采用UUO致肾间质纤维化大鼠模型,将81只大鼠随机分假手术组、模型组、治疗组。治疗组于术后第1天开始给予双环醇200 mg.kg-1灌胃;假手术组和模型组给予等量生理盐水灌胃。在术后7,14,21 d每组各取9只大鼠处死,取梗阻侧肾组织行HE及Masson染色,观察肾脏病理学变化。用免疫组化方法检测肾组织NF-κB,PAI-1蛋白的表达。RT-PCR法检测各组肾组织PAI-1 mRNA的表达水平。结果:模型组7,14,21 d肾间质纤维化的相对面积分别为(13.03±0.66)%,(25.76±1.47)%,(53.16±2.45)%,治疗组分别为(9.63±0.58)%,(16.84±0.83)%,(33.59±1.61)%,治疗组较模型组肾间质纤维化的相对面积明显降低(P<0.05)。7,14,21 d模型组肾组织NF-κB的表达分别为(11.73±0.42)%,(22.56±0.69)%,(36.27±1.14)%,而治疗组分别为(5.67±0.42)%,(10.79±0.37)%,(26.62±0.23)%;模型组肾组织PAI-1蛋白的表达分别为(7.29±0.23)%,(12.32±0.20)%,(18.36±0.19)%,治疗组分别为(4.26±0.14)%,(7.69±0.13)%,(13.35±0.21)%;肾组织PAI-1 mRNA在模型组的表达分别为(1.17±0.10),(2.29±0.07),(3.33±0.10),而治疗组的表达分别为(0.32±0.03),(1.18±0.05),(2.06±0.40),治疗组肾组织NF-κB,PAI-1蛋白和mRNA的表达均较模型组减少(P均<0.05)。结论:双环醇能够减轻UUO所致的肾间质损伤及纤维化的程度。其作用机制可能是通过下调NF-κB,PAI-1的表达,从而抑制肾间质纤维化。
OBJECTIVE: To investigate the effects of bicyclol on unilateral ureteral obstruction (UUO) rats. To observe the effects of bicyclol on the expression of nuclear factor-κB (NF-κB), plasminogen activator inhibitor-1 plasminogen activator inhibitor-1, PAI-1) and PAI-1 mRNA in the interstitium of obstructive kidney, and explore the possible mechanism of bicyclol delaying renal interstitial fibrosis. Methods: UUO induced renal interstitial fibrosis rats model, 81 rats were randomly divided into sham operation group, model group and treatment group. In the treatment group, 200 mg · kg-1 bicyclol was given to the rats on the first day after operation. The rats in the sham operation group and model group were given the same amount of normal saline. At the 7th, 14th and 21st day after operation, 9 rats in each group were sacrificed, and obstructed kidney tissues were stained with HE and Masson to observe the renal pathological changes. Immunohistochemistry was used to detect the expression of NF-κB and PAI-1 in renal tissue. The expression of PAI-1 mRNA in each group was detected by RT-PCR. Results: The relative area of renal interstitial fibrosis in model group was (13.03 ± 0.66)%, (25.76 ± 1.47)% and (53.16 ± 2.45)% on the 7th, 14th and 21st day respectively in the model group and (9.63 ± 0.58) %, (16.84 ± 0.83)% and (33.59 ± 1.61)%, respectively. The relative area of renal interstitial fibrosis in treatment group was significantly lower than that in model group (P <0.05). The expression of NF-κB in the model group was (11.73 ± 0.42)%, (22.56 ± 0.69)%, (36.27 ± 1.14)% on the 7th, 14th and 21st day respectively, while it was 5.67 ± 0.42% (10.79 ± 0.37)% and (26.62 ± 0.23)%, respectively. The expression of PAI-1 in the model group was (7.29 ± 0.23)%, (12.32 ± 0.20)% and (4.26 ± 0.14)%, (7.69 ± 0.13)% and (13.35 ± 0.21)%, respectively. The expression of PAI-1 mRNA in renal tissue was (1.17 ± 0.10), (2.29 ± 0.07) and 0.10). The expressions of NF-κB, PAI-1 protein and mRNA in the treatment group were significantly lower than those in the untreated group (0.32 ± 0.03, 1.18 ± 0.05, 2.06 ± 0.40, P <0.05). Conclusion: Bicyclol can relieve renal interstitial injury and fibrosis induced by UUO. Its mechanism may be through the down-regulation of NF-κB, PAI-1 expression, thereby inhibiting renal interstitial fibrosis.