机构地区:[1]河南省中医院肾病科,河南郑州450002 [2]中南大学湘雅医院放射科,湖南长沙410008 [3]中国人民解放军总医院肾脏病科(肾脏疾病国家重点实验室),北京100853
出 处:《中国现代医学杂志》2015年第30期7-12,共6页China Journal of Modern Medicine
基 金:河南省中医药科学研究专项课题(No:2014ZY02021)
摘 要:目的观察当归补血汤(DBD)对尿毒症大鼠心肌组织瞬时受体电位M7通道(TRPM7)表达及胶原蛋白合成的影响,探讨DBD抗尿毒症心肌纤维化(UMF)作用机制。方法采用腺嘌呤核苷酸灌胃制作尿毒症模型,雄性SD大鼠32只,随机分为对照组、模型组、依那普利组及DBD组。依那普利和DBD组自造模第1天开始分别以依那普利10 mg/(kg·d)或DBD 6 g/(kg·d)灌胃;直至第21天,模型组和对照组以等体积的生理盐水灌胃。造模后第21天处死大鼠,留取血液标本检测血清尿素氮(BUN)、肌酐(Scr)和心肌肌钙蛋白Ⅰ(c TnⅠ)。留取心肌标本,行苏木精-伊红染色(HE)和Masson染色,观察各组大鼠心肌组织病理改变。采用实时定量逆转录-聚合酶链反应(RT-PCR)检测心肌组织TRPM7 m RNA和转化生长因子-β1(TGF-β1)m RNA的表达。应用Western blot检测心肌组织TRPM7、Ⅰ型胶原蛋白(ColⅠ)和Ⅲ型胶原蛋白(ColⅢ)的表达。结果与对照组比较,模型组大鼠心肌病理评分增加,心肌间质胶原蛋白相对面积增大,血清BUN、Scr和(c TnⅠ)水平提高,TRPM7 m RNA和TGF-β1m RNA的表达增强,心肌组织TRPM7、ColⅠ和ColⅢ的表达增强。与模型组比较,经依那普利和DBD治疗后,心肌组织病理评分和心肌间质胶原蛋白相对面积缩小,血清BUN、Scr和c TnⅠ水平下降,TRPM7 m RNA和TGF-β1m RNA的表达减弱,心肌组织TRPM7、ColⅠ和ColⅢ的表达减弱,差异有统计学意义(P<0.05)。与依那普利组比较,DBD组能明显降低TGF-β1m RNA的表达。结论 DBD可减轻尿毒症大鼠心肌纤维化程度,这一作用与抑制心肌组织TRPM7表达,从而抑制胶原蛋白合成有关。【Objective】 To investigate the effect of Danggui Buxue Decoction(DBD) on the expression of transient receptor potential melastatin 7(TRPM 7) and collagen synthesis in rats of uremia myocardial fibrosis(UMF).【Methods】 UMF model was induced by gavage of adenine nucleotide.Male Sprague-Dawley rats(n =32) were randomly divided into control group,UMF model group,Enalapril group and Danggui Buxue Decoction(DBD) group.The rats were treated with Enalapril 10 mg/(kg·d) or DBD 6 g/(kg·d)by gastric gavage in the Enalapril group and Danggui Buxue Decoction group,respectively.The rats were treated with identical dose of normal saline in the control and model groups.All the rats were sacrificed on the 21 st day.Serum creatinine(Scr),urea nitrogen(BUN) and troponin Ⅰ(c TnⅠ) were measured.Pathological changes of the myocardial tissue were observed under light microscopy by HE and Masson staining.The expressions of TRPM 7m RNA and TGF-β1m RNA were detected by real-time PCR.The expressions of TRPM 7,collagen Ⅰ(ColⅠ) and collagen Ⅲ(Col Ⅲ) were detected by Western blot.【Results】 Compared with the control group,serum creatinine,urea nitrogen and troponin Ⅰ,the myocardial tissue pathologial damage index,relative collagen area,the expressions of TRPM 7 m RNA and TGF-β1m RNA and the levels of TRPM 7,Col Ⅰ and Col Ⅲ in the uremia myocardial tissue significantly increased in the model group(P 0.05).After the treatment by Enalapril and DBD,there were significant reductions in myocardial tissue damage index,relative collagen area and the levels of BUN,Scr and c Tn Ⅰin the Enalapril group and DBD group(P 0.05).Meanwhile,Enalapril and DBD inhibited the expression of TRPM7 m RNA,TGF-β1m RNA,TRPM 7,Col Ⅰ and Col Ⅲ compared with the model group(P 0.05).Compared with the Enalapril group,DBD attenuated the expression of TGF-β1m RNA.【Conclusions】 DBD significantly attenuates myocardial fibrosis by supressing the expression of TRPM 7 and then am
关 键 词:心肌纤维化 尿毒症 瞬时受体电位M7通道 当归补血汤
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