西安交通大学学报（医学版）
西安交通大學學報（醫學版）
서안교통대학학보（의학판）
Journal of Xi'an Jiaotong University (Medical Sciences)
2015年
6期
765-769,800
,共6页
肾性贫血%促红细胞生成素%BMP/SMAD%铁调素%骨形态蛋白-6(BMP-6)
腎性貧血%促紅細胞生成素%BMP/SMAD%鐵調素%骨形態蛋白-6(BMP-6)
신성빈혈%촉홍세포생성소%BMP/SMAD%철조소%골형태단백-6(BMP-6)
renal anemia%erythropoietin%BMP/SMAD%hepcidin%BMP-6
目的：探讨促红细胞生成素(EPO)对肾性贫血大鼠肾脏的保护作用及其可能的作用机制。方法将实验大鼠随机分为对照组(NC 组,n=18)和实验组(n=72),采用腺嘌呤注射建立肾性贫血大鼠模型,再随机分为单纯贫血组(SA 组)、铁剂+促红素组(IR+EPO 组)、促红素组(EPO 组)、铁剂组(IR 组)。药物干预4周后,处死大鼠(心脏取血),自动化血液分析仪检测血清肌酐(Scr)、尿素氮(Bun)、血红蛋白(Hb)、血细胞比容(Hct)；ELISA 法检测铁调素(Hepcidin)。免疫组织化学染色法和 Western blot 法分别检测大鼠肾脏骨形态蛋白-6(BMP-6)、丝/苏氨酸激酶受体-1(SMAD-1)和 SMAD-4的表达。结果①一般指标的比较：与 SA 组相比较,IR+EPO 组和 EPO 组 BUN、Scr 显著降低(P <0.01)；IR+EPO 组和 EPO 组 Hb、Hct 显著升高(P <0.01)。②ELISA 法检测示 IR+EPO 组和 EPO 组铁调素显著降低(P <0.01)。③病理学观察提示 EPO 可以减轻大鼠肾脏病理及功能改变。④免疫组织化学染色示各组大鼠肾小球细胞胞质和肾小管上皮细胞内均表达 SMAD-4、SMAD-1、BMP-6。⑤Western blot 进一步提示,与 SA组相比,IR+EPO 组和 EPO 组 SMAD-4蛋白表达量显著下调(P <0.01),IR+EPO 组和 EPO 组 SMAD-1蛋白表达量下调(P <0.05),IR+EPO 组和 EPO 组 BMP-6蛋白表达量显著上调(P <0.01)。结论EPO 通过 BMP/SMAD 传导通路,抑制铁调素的表达及分泌,纠正贫血,发挥肾脏保护作用。
目的：探討促紅細胞生成素(EPO)對腎性貧血大鼠腎髒的保護作用及其可能的作用機製。方法將實驗大鼠隨機分為對照組(NC 組,n=18)和實驗組(n=72),採用腺嘌呤註射建立腎性貧血大鼠模型,再隨機分為單純貧血組(SA 組)、鐵劑+促紅素組(IR+EPO 組)、促紅素組(EPO 組)、鐵劑組(IR 組)。藥物榦預4週後,處死大鼠(心髒取血),自動化血液分析儀檢測血清肌酐(Scr)、尿素氮(Bun)、血紅蛋白(Hb)、血細胞比容(Hct)；ELISA 法檢測鐵調素(Hepcidin)。免疫組織化學染色法和 Western blot 法分彆檢測大鼠腎髒骨形態蛋白-6(BMP-6)、絲/囌氨痠激酶受體-1(SMAD-1)和 SMAD-4的錶達。結果①一般指標的比較：與 SA 組相比較,IR+EPO 組和 EPO 組 BUN、Scr 顯著降低(P <0.01)；IR+EPO 組和 EPO 組 Hb、Hct 顯著升高(P <0.01)。②ELISA 法檢測示 IR+EPO 組和 EPO 組鐵調素顯著降低(P <0.01)。③病理學觀察提示 EPO 可以減輕大鼠腎髒病理及功能改變。④免疫組織化學染色示各組大鼠腎小毬細胞胞質和腎小管上皮細胞內均錶達 SMAD-4、SMAD-1、BMP-6。⑤Western blot 進一步提示,與 SA組相比,IR+EPO 組和 EPO 組 SMAD-4蛋白錶達量顯著下調(P <0.01),IR+EPO 組和 EPO 組 SMAD-1蛋白錶達量下調(P <0.05),IR+EPO 組和 EPO 組 BMP-6蛋白錶達量顯著上調(P <0.01)。結論EPO 通過 BMP/SMAD 傳導通路,抑製鐵調素的錶達及分泌,糾正貧血,髮揮腎髒保護作用。
목적：탐토촉홍세포생성소(EPO)대신성빈혈대서신장적보호작용급기가능적작용궤제。방법장실험대서수궤분위대조조(NC 조,n=18)화실험조(n=72),채용선표령주사건립신성빈혈대서모형,재수궤분위단순빈혈조(SA 조)、철제+촉홍소조(IR+EPO 조)、촉홍소조(EPO 조)、철제조(IR 조)。약물간예4주후,처사대서(심장취혈),자동화혈액분석의검측혈청기항(Scr)、뇨소담(Bun)、혈홍단백(Hb)、혈세포비용(Hct)；ELISA 법검측철조소(Hepcidin)。면역조직화학염색법화 Western blot 법분별검측대서신장골형태단백-6(BMP-6)、사/소안산격매수체-1(SMAD-1)화 SMAD-4적표체。결과①일반지표적비교：여 SA 조상비교,IR+EPO 조화 EPO 조 BUN、Scr 현저강저(P <0.01)；IR+EPO 조화 EPO 조 Hb、Hct 현저승고(P <0.01)。②ELISA 법검측시 IR+EPO 조화 EPO 조철조소현저강저(P <0.01)。③병이학관찰제시 EPO 가이감경대서신장병리급공능개변。④면역조직화학염색시각조대서신소구세포포질화신소관상피세포내균표체 SMAD-4、SMAD-1、BMP-6。⑤Western blot 진일보제시,여 SA조상비,IR+EPO 조화 EPO 조 SMAD-4단백표체량현저하조(P <0.01),IR+EPO 조화 EPO 조 SMAD-1단백표체량하조(P <0.05),IR+EPO 조화 EPO 조 BMP-6단백표체량현저상조(P <0.01)。결론EPO 통과 BMP/SMAD 전도통로,억제철조소적표체급분비,규정빈혈,발휘신장보호작용。
Objective To investigate the protective effect of erythropoietin (EPO)on the kidney of renal anemia rats and further explore the renoprotective action and possible mechanisms.Methods A total of 90 SD rats were randomly divided into 5 groups:normal control rats (NC),simple anemia group (SA),iron + EPO group (IR+EPO),erythropoietin group (EPO),and iron group (IR)with 18 in each.The rats were sacrificed after 4 weeks’ treatment with intragastrically-injected adenine.Serum creatinine (Scr),blood urea nitrogen (Bun),hemoglobin (Hb),hematocrit (Hct),and hepcidin were measured with automated hematology analyzer.The expressions of bone morphogenetic protein-6 (BMP-6 ),a serine/threonine kinase receptor-1 (SMAD-1 )and serine/threonine kinase receptor-4 (SMAD-4)in the kidney were detected by immunohistochemistry and Western blot.Results ①The results of general indicators:BUN and Scr in IR + EPO group and EPO group were lower than those in SA group (P <0.01).Hb and Hct in IR + EPO group and EPO group were increased significantly compared with those in SA group (P <0.01).Hepcidin was significantly increased in simple anemia group (P <0.01).② ELISA results showed that Hepcidin was lower in IR + EPO group and EPO group than in SA group (P <0.01).③ The results of pathological observation indicated that EPO could reduce rat renal pathology and function.④ Immunohistochemistry revealed that SMAD-4,SMAD-1 and BMP-6 were expressed in the rat glomerular cells and renal tubular epithelial cells.⑤ Western blot further indicated that the expression of SMAD-4 was significantly decreased in IR + EPO group and EPO group (P < 0.01 ).The expression of SMAD-1 in IR+EPO group and EPO group was decreased (P <0.05)while that of BMP-6 was elevated in IR+EPO group and EPO group (P <0.01 ).Conclusion The expression and secretion of hepcidin were inhibited by EPO via the BMP/SMAD pathway,which further corrects anemia and exerts a renal protective effect.
