摘要
目的观察补肾活血方对慢性肾衰竭大鼠血管钙化(vascular calcification,VC)的BMP-2/Runx2/Osterix信号通路作用,探讨其可能的作用机制。方法将30只SD大鼠随机分为正常组、模型组与中药组,每组10只。模型组与中药组大鼠实验第1~4周给予250 mg/kg腺嘌呤混悬液灌胃及含1.8%高磷饲料每日1次喂养,第5~8周腺嘌呤改为隔日灌胃。中药组同时按55 g/(kg·d)剂量给予补肾活血方灌胃治疗,每日1次。正常组灌胃等量生理盐水。共给药8周。HE染色观察肾组织变化,茜素红染色观察主动脉钙化结节情况,腹主动脉取血检测血清钙(Ca)、磷(P)、血肌酐(SCr)、尿素氮(BUN)、全段甲状旁腺激素(i PTH),Western blot法检测骨形态发生蛋白-2(bone morphogenetic protein,BMP-2)及其下游调节因子即核心结合因子(Runt related transcription factor,Runx2)、成骨细胞特异性转录因子(Osterix)蛋白的表达。结果 HE染色观察提示:与正常组比较,模型组肾小球结构紊乱,肾小管扩张积水,腔内有炎性细胞的浸润,肾小管内棕褐色结晶沉积,肾脏间质纤维化,肾脏血管明显减少;与模型组比较,中药组正常肾小球数目增多,肾小管扩张程度降低,炎性细胞数量下降,腺嘌呤结晶减少。茜素红染色观察提示:与正常组比较,模型组主动脉出现钙化结节,广泛红色颗粒物沉着;与模型组比较,中药组钙化结节减少。与正常组比较,模型组大鼠血P、SCr、BUN、i PTH水平均明显升高,血Ca水平明显下降,BMP-2、Runx2、Osterix蛋白表达亦增高(P〈0.05,P〈0.01);与模型组比较,中药组血清P、SCr、BUN、i PTH水平均明显下降,血Ca水平明显升高,BMP-2、Runx2、Osterix蛋白表达均降低(P〈0.05,P〈0.01)。结论补肾活血方能够改善慢性肾衰竭大鼠肾功能和钙磷代谢,改善肾脏组织学结果,下调BMP-2/Runx2/Osterix信号通路在慢性肾衰竭VC中的表达,这可能是其�
Objective To observe the effect of Bushen Huoxue Recipe( BHR) on inhibiting vascular calcification( VC) in chronic renal failure( CRF) rats by regulating BMP-2 /Runx2 /Osterix signal pathway,and to explore its possible mechanism. Methods Thirty SD rats were randomly divided into the normal group,the model group,and the BHR group,10 in each group. Rats in the model group and the BHR group were administered with 250 mg / kg adenine suspension bygastroagavage and fed with 1. 8% high phosphorus forage,once per day in the first 4 weeks,and then gastric administration of adenine suspension was changed to once per two days in the following 5- 8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g / kg by gastrogavage in the first 8 weeks,once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium( Ca),phosphorus( P),serum creatinine( Cr),blood urea nitrogen( BUN),and intact parathyroid hormone( i PTH) in serum were detected. Protein expression levels of bone morphogenetic protein( BMP-2),Runt related transcription factor( Runx2),and Osterix were detected by Western blot. Results HE staining showed that compared with the normal group,disordered glomerular structure,tubular ectasia and dropsy,intracavitary inflammatory cell infiltration,dark brown crystal deposition in kidney tubules,renal interstitial fibrosis,and decreased number of renal blood vessels in the model group. Compared with the model group,normal glomerular numbers increased more,reduced degree of tubular ectasia,decreased number of inflammatory cells,and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group,calcified nodes could be found in the model group,with extensive deposition of red particle in aorta. Compared with the model group,calci
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2016年第3期327-332,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(No.81273747)
中国中医科学院博士研究生创新人才培养基金资助项目(No.CX201506)