摘要
目的:研究中药复方肾衰泄浊汤及其拆方对Wnt/β-catenin信号通路中MMP7、PAI-1因子及该信号通路中β-catenin的表达影响,阐述肾衰泄浊汤抗肾间质纤维化的机理。方法:采用单侧输尿管梗阻动物模型,将SD雌性大鼠72只按体质量随机分为:假手术组、模型组、肾衰泄浊汤组、补虚方组、袪邪方组、盐酸贝那普利组,每组12只,各组大鼠分别于术后第7、14天处死,取肾脏组织行HE、Masson染色,光镜下观察肾脏组织病理改变,并测定肾小管间质纤维化指数;免疫组化法检测β-catenin、MMP7及PAI-1蛋白在肾间质的表达情况,另采用原位杂交法检测各组大鼠肾组织β—cateninmRNA的表达。结果:经HE、Masson染色后,从不同时间段观察模型组及各治疗组的病理表现,术后7 d相对以炎症和坏死病变为主,术后14 d以纤维化和炎症为主,特别是模型组更为明显,假手术组在各时期无明显病理改变。免疫组化结果显示,各治疗组大鼠肾组织MMP7蛋白阳性表达均高于模型组,以肾衰泄浊汤组更加明显(均P<0.05);而PAI-1蛋白阳性表达均低于模型组,尤以肾衰泄浊汤组更佳(均P<0.05)。原位杂交结果:模型组及各治疗组大鼠β-cateninmRNA表达明显高于假手术组(均P<0.05),各治疗组β-cateninmRNA表达较同时期的模型组减少显著(均P<0.05),尤以肾衰泄浊汤组更明显。结论:复方肾衰泄汤可通过调节UUO大鼠肾间质的MMP7、PAI-1蛋白及β-catenin的表达,减少细胞外基质的沉积,从而达到抗肾间质纤维化的作用。
Objective: To study the effect of Chinese medicine formula Shenshuai Xiezhuo Decoction and its different components on the expressions of MMP7,PAI-1 and β-catenin in the signal pathway of Wnt/β-catenin and elucidate the mechanism of Shenshuai Xiezhuo Decoction against renal interstitial fibrosis. Methods: The animal models of unilateral ureteral obstruction to SD female rats were randomly divided into 72 according to the weight: control group, model group,Shenshuai Xiezhuo Decoction,expelling evils group,tonifying deficiency group,hydrochloric acid captopril group, 12 in each group. The rats were killed respectively 7 and 14 days after the operation. HE and Masson staining were used to observe the renal tissue and then we observed kidney tissue pathological changes and determined the index of renal tubule interstitial fibrosis.β-catenin, MMP7 and PAI-1 proteins were detected by immunohistochemical assay in the renal interstitium. In addition, in situ hybridization method was used to detect the expression of β-cateninmRNA in the renal tissue of each group. Results: After HE and Masson staining, in different time periods we observed the pathological performance of model group and treatment group, 7 d after operation inflammation and necrosis were the main pathological changes. And fibrosis and inflammation were the main changes 14 d after operation, especially in the model group. No obvious pathological changes were observed in the sham group at any time. The results of immunohistochemistry showed that the positive expression of MMP7 protein in the renal tissue of rats in each treatment group was higher than that of the model group. The positive expression of PAI-1 protein was lower than that of the model group, especially the Shenshuai Xiezhuo Decoction group(P<0.05). In situ hybridization results: The model group and treatment group’s β-cateninmRNA expressions were significantly higher than that of the control group(P<0.05). The treatment groups’β-cateninmRNA expression reduced significantly compared with that of the model group(P<0.05), especially the Shenshuai Xiezhuo Decoction group. Conclusion:Shenshuai Xiezhuo Decoction can reduce the deposition of extracellular matrix by regulating the expressions of MMP7, PAI-1 protein and β-catenin in the renal interstitial of UUO rats so as to achieve the effect of anti-renal interstitial fibrosi.
作者
黄伟
沈金峰
罗富里
晏子友
HUANG Wei;SHEN Jinfeng;LUO Fuli;YAN Ziyou(Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,Jiangxi,China;The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330000,Jiangxi,China)
出处
《中华中医药学刊》
CAS
北大核心
2019年第5期1079-1082,I0006-I0007,共5页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81660769)
江西省自然科学基金项目(20161BAB205274)
