清化固肾排毒方对单侧输尿管梗阻大鼠肾间质纤维化的保护作用及机制

Protective Effect of Qinghua Gushen Paidu Decoction on Renal Interstitial Fibrosis in Unilateral Ureteral Obstruction Rat Model and Its Mechanism

目的:观察清化固肾排毒方对单侧输尿管梗阻大鼠肾间质纤维化的保护作用及机制。方法:108只SPF级SD大鼠随机分为假手术组、UUO模型组、中药高剂量组、中剂量组、低剂量组、洛丁新组,给予相应药物治疗,各组分别于建模后第7、14、21天处死,留取血清测Scr、BUN,留取梗阻侧肾组织行HE和Masson染色,光镜观察各组大鼠肾组织病理变化。免疫组化检测肾组织TGF-β_1、Smad2/3、Smad7的表达。结果:随着输尿管梗阻时间延长,肾小管间质纤维化程度逐渐加重。免疫组化结果显示:与假手术组相比,各时相点UUO组TGF-β1、Smad2/3表达明显上升,Smad7表达明显下降(P均<0.05);药物干预后,与UUO组相比,中药治疗组和洛丁新组TGF-β_1、Smad2/3表达下降,Smad7表达上升(P均<0.05);中药各剂量组与洛丁新组之间比较无统计学差异。结论:清化固肾排毒方可能通过下调Smad2/3及上调Smad7来抑制TGF-β_1/Smads信号转导通路,发挥改善肾间质纤维化的作用。

Objective： To investigate the protective effects of Qinghua Gushen Paidu Decoction on renal interstitial fibrosis in a unilateral ureteral obstruction（UUO） rat model and its mechanism. Methods： 108 male SPF grade Sprague - Dawley （SD） rats were randomly subdivided into a sham -operated group, a model group, the high, middle and low dose groups of Qinghua Gushen Paidu decoction and Lotensin treated group. All rats were sacrificed 7,14 and 21 days after surgery. Scr and BUN were measured. The pathological changes of the obstruction renal tissue were examined by HE and Masson staining. The protein expressions of TGF- β1, Smad2/3 and Smad7 were detected by immunohistochemical stai- ning. Results： The renal interstitial fibrosis degree was gradually aggregated along with the ureteral obstruction time. Compared with the sham group, the protein expressions of TGF-β1 and Smad2/3 were increased significantly, but Smad7 was decreased significantly in UUO group in each sacrifice time （ all P 〈 0. 05 ）. After the treatment by drugs, compared with UUO group, the protein expressions of TGF - β1 and Smad2 were decreased significantly and Smad7 increased significantly in Qinghua Gushen Paidu Decoction groups and Lotensin treated group （ all P 〈 0. 05 ）. No significant difference in effect on indexes was observed among Qinghua Gushen Paidu Decoction groups and Lotensin treated group. Conclusion： Qinghua Gushen Paidu Decoction may protect the kidney by up - regulating the expression of Smad2/3 and down - regula- i ting the expression of Smad7 to inhibit the TGF - β1/Smads signal transduction passway and ameliorate renal interstitial fibrosis.