摘要
目的探讨益肾化瘀方抗肾间质纤维化的可能作用机制。方法 108只SD大鼠随机分为假手术组、模型组、缬沙坦组和益肾化瘀方高、中、低剂量组,每组18只。除假手术组外其余大鼠采用单侧输尿管结扎方法建立肾间质纤维化模型,造模次日益肾化瘀方高、中、低剂量组分别予益肾化瘀方浓缩液32、16、8 g/(kg·d)灌胃,缬沙坦组予缬沙坦溶液13.3 mg/(kg·d)灌胃,假手术组、模型组予生理盐水20 ml/(kg·d)灌胃,各组均连续灌胃28天。分别于造模后第7、14、28天观察大鼠肾组织病理改变,计算肾间质纤维化面积,检测大鼠肾组织中转化生长因子β1(TGF-β1)、Smad7信号蛋白的表达。结果模型组大鼠出现肾间质炎细胞浸润和梭形核细胞增生,伴局灶性肾间质纤维化,各治疗组肾脏病理表现均有不同程度的减轻,其中益肾化瘀方高剂量组病理改变与缬沙坦组相当。与同时间点假手术组比较,其余各组大鼠肾间质纤维化面积、TGF-β1升高,Smad7信号蛋白减少(P<0.01);与同时间点模型组比较,除益肾化瘀方低剂量组外,其余各治疗组大鼠肾间质纤维化面积、TGF-β1降低,Smad7信号蛋白增加(P<0.05或P<0.01),并且以益肾化瘀方高剂量组和缬沙坦组改善最明显(P<0.05)。结论益肾化瘀方可能通过抑制大鼠肾组织中TGF-β1的高表达,上调Smad7的表达,从而减轻肾间质纤维化。
Objective To study the possible mechanism of Yishen Huayu Formula （formula to supplement the kidney and transform stasis） for renal interstitial fibrosis. Methods Totally 108 Sprague Dawley rats were randomized into the sham operation group, model group, valsartan group and Yishen Huayu Formula high-dose, middle-dose and low-dose groups, with 18 in each. The models of renal interstitial fibrosis were established by unilateral ureteral obstruction in all groups except the sham operation group. On the 2nd day after modeling, Yishen Huayu Fbrmula high- dose, middle-dose and low-dose groups were garaged with 32g/kg · d, 16 g/kg · d and 8 g/kg · d of Yishen Huayu Formula coneentrated solution respectively, valsartan group was garaged with 13.3 mg/kg · d of valsartan solution and sham operation group and model group were garaged with 20 ml/ kg · d of normal saline for 28 days. The pathological changes in kidney tissue were observed on the 7th, 14th, and 28th day after modeling. The renal interstitial fibrosis area was calculated. The expressions of transforming growth factor-β1 （TGF-β1） and Smad7 signaling proteins were detected. Results There were renal interstitial infiltration of inflammatory cells, spindle nucleated cell prolil〉ration and focal renal interstitial fibrosis in the model group. The pathological manifestations were reduced in all medication groups. The pathological changes in Yishen Huayu Formula high-dose group were the same as in valsartan group. Comparing with the sham operation group, the renal interstitial fibrosis areas and TGF-β1 levels were signific.zmtly in- creased and the Smad7 levels were significantly decreased in other groups （P 〈0. 01 ）. Comparing with the model group at the same time point, the renal interstitial fibrosis areas and TGF-β1 levels were significantly decreased and the Smad7 levels were significantly increased in all medication groups （ P 〈 0. 05 or P 〈 0. 01 ）, especially in Yishen Huayu Formula high-dose group and valsartan group （P 〈 0. 05 ）. Conclusion Yishen Huayu Formula can reduce renal interstitial fibrosis possibly by inhibiting the expression of TGF-β1 and up-regulating the expression of Smad7.
出处
《中医杂志》
CSCD
北大核心
2014年第17期1498-1501,共4页
Journal of Traditional Chinese Medicine
基金
河南省教育厅自然科学研究项目(2011A360023)
河南省基础与前沿技术研究项目(102300410124)
关键词
益肾化瘀方
单侧输尿管结扎
肾间质纤维化
转化生长因子Β1
Smad7信号蛋白
Keywords Yishen Huayu Formula
unilateral ureteral obstruction
renal interstitial fibrosis
transforming growthfactor-J31
Smad7 signaling proteins
