摘要
目的:研究肾衰泄浊汤及其补虚,祛邪组分对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响。方法:通过结扎单侧输尿管建立UUO大鼠模型。SD大鼠随机分为6组,分别为假手术组,模型组,贝那普利组,肾衰泄浊汤组,补虚方组,袪邪方组;每组24只。手术后第3天,肾衰泄浊汤组,补虚方组,袪邪方组大鼠均按0. 8 g·mL^-1肾衰泄浊汤浓缩剂给药,即给药剂量为8. 0 g·kg^-1·d^-1体质量灌胃;贝那普利组大鼠给贝那普利1. 5 mg·kg^-1·d^-1体质量灌胃,假手术组,模型组大鼠给等量生理盐水灌胃。术后第7,14,21天,分别用蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测肾组织中周细胞及相关信号通路标志物表达情况。结果:与模型组比较,肾衰泄浊汤组,补虚方组,袪邪方组在UUO后第14,21天的间质损伤评分和间质胶原的积累均显著降低(P<0. 05)。除假手术组外,各组在第14,21天的肾组织中α-平滑肌肌动蛋白(α-SMA),血小板衍生生长因子A(PDGFA),神经/胶质细胞2型硫酸软骨素糖蛋白(NG-2),血管内皮生长因子A(VEGFA),血管内皮生长因子受体1(VEGFR1),血小板源性生长因子β(PDGF-β),血小板源性生长因子受体β(PDGFR-β)的蛋白表达均较第7天显著增加(P<0. 05)。在手术后第21天,肾衰泄浊汤组的肾组织中NG-2,VEGFA,VEGFR1,PDGFR-β蛋白表达均显著低于模型组(P<0. 05)。与模型组比较,肾衰泄浊汤组在手术后第21天的肾组织中α-SMA,PDGFA,NG-2,VEGFA,VEGFR1,PDGF-β,PDGFR-βmRNA相对表达量均显著降低(P<0. 05),并且肾衰泄浊汤组在手术后第21天α-SMA,NG-2,VEGFA,VEGFR1,PDGFR-βmRNA相对表达量显著低于贝那普利组(P<0. 05)。结论:肾衰泄浊汤复方及其补虚,祛邪组分对UUO大鼠肾间质纤维化均具有拮抗作用,其作用机制与抑制周细胞及其相关细胞信号通路激活有关。
Objective:To study the effect of Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components on renal interstitial fibrosis in UUO rats. Method: A rat model of unilateral ureteral obstruction(UUO)was established through ligation of a unilateral ureter. The rats were divided into six groups:sham operation group,model group,benazepril group,Shenshuai Xiezhuo decoction group,Buxufang group,and phlegm group,with 24 rats in each group. On the third day after operation,the rats in the Shenshuai Xiezhuo decoction group,Buxufang group,and phlegm group were given Shenshuai Xiezhuo decoction concentrating agent at a dose of 8. 0 g·kg^-1·d^-1,the rats in the benazepril group were given benazepril 1. 5 mg·kg^-1·d^-1,and the rats in the sham operation group and the model group were given the same volume of saline. On the 7 th,14 thand 21 stdays after operation,the expressions of peripheral cells and relevant signal pathway markers in renal tissue were detected by Western blot and Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR)respectively. Result: The stromal damage score and the interstitial collagen accumulation on the 14 thand 21 stdays after UUO were significantly lower in the Shenshuai Xiezhuo decoction group,Buxu prescription group and Qixie prescription group than those in the model group(P<0. 05). Except for the sham operation group,the protein expressions of α smooth muscle actin(α-SMA),platelet derived growth factor A(PDGFA),nerve/glial type 2 chondroitin sulfate glycoprotein(NG-2),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor 1(VEGFR1),plateletderived growth factor-β(PDGF-β)and platelet-derived growth factor receptor-β(PDGFR-β)in the kidney tissues of the 14 thand 21 stdays were significantly increased compared with those on the 7 thday(P<0. 05). On the 21 stday after surgery,the expressions of NG-2,VEGFA,VEGFR1 and PDGFR-β in renal tissue of Shenshuai Xiezhuo decoction group were significantly lower than those in the model group(P<0. 05).Compared with the model group,relevant expressions of α-SMA,PDGFA,NG-2,VEGFA,VEGFR1,PDGF-β,and PDGFR-β in kidney tissue of Shenshuai Xiezhuo decoction group decreased significantly on the 21 stday after operation(P<0. 05),and relative expressions of α-SMA,NG-2,VEGFA,VEGFR1 and PDGFR-β in the Shenshuai Xiezhuo decoction group were significantly lower than those in the benazepril group on the 21 stday after surgery(P<0. 05). Conclusion: Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components have an antagonistic effect on renal interstitial fibrosis in UUO rats. Its mechanism is related to the inhibition of activation of peripheral cells and relevant cell signaling pathways.
作者
晏子友
江坚青
罗富里
皮持衡
YAN Zi-you;JIANG Jian-qing;LUO Fu-li;PI Chi-heng(Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,China;Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第16期71-78,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金地区基金项目(81660769)。
关键词
肾衰泄浊汤
血管周细胞
单侧输尿管梗阻
肾间质纤维化
Shenshuai Xiezhuo decoction
perivascular cells
unilateral ureteral obstruction
renal interstitial fibrosis
