中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
4期
531-535
,共5页
李荣霏%曹春芽%谭艳辉%刘志华
李榮霏%曹春芽%譚豔輝%劉誌華
리영비%조춘아%담염휘%류지화
大豆异黄酮%nephrin%肿瘤坏死因子 α%NF-κB
大豆異黃酮%nephrin%腫瘤壞死因子 α%NF-κB
대두이황동%nephrin%종류배사인자 α%NF-κB
soybean isofIavone%nephrin%tumor necrosis factor-α%NF-κB
目的:观察大豆异黄酮(SI)对糖尿病大鼠肾组织 nephrin 表达的影响,探讨其对糖尿病肾病治疗作用的机制。方法健康 SD 大鼠一次性尾静脉注射链佐星60 mg·kg-1制备糖尿病大鼠模型,72 h 后分别 ig 给予 SI 40,120和360 mg·kg-1,每天1次,连续8周。8周后,血糖仪检测空腹血糖(FBG)水平;ELISA 法检测24 h 尿蛋白(UP);全自动生化分析仪检测血肌酐(SCr)、尿素氮(BUN)、丙二醛(mDA)和超氧化物歧化酶(SOD)含量;Western 蛋白质印迹法检测肾组织 nephrin、肿瘤坏死因子α(TNF-α)及 NF-κB蛋白表达。结果与正常对照组相比,糖尿病模型对照组 FBG,24 h UP,BUN,SCr 及 mDA 均明显升高(P﹤0.05,P﹤0.01),SOD 水平明显降低(P﹤0.01)。与模型对照组相比,SI 40,120和360 mg·kg-1组BUN 水平明显降低( P ﹤0.05,P ﹤0.01),由(24.3±6.3)mmoI·L-1分别降至16.8±4.9,13.4±5.4和(7.7±1.2)mmoI·L-1;SI 360 mg·kg-1组24 h UP 由(1.26±0.45)mg 显著降低至(0.88±0.15)mg( P﹤0.01),SCr 由(56.4±8.4)μmoI·L-1显著降低至(35.3±4.3)μmoI·L-1( P ﹤0.01),mDA 水平由(8.32±1.40)μmoI·L-1显著降低至(5.33±0.95)μmoI·L-1( P ﹤0.01);SI 120和360 mg·kg-1组 SOD 水平由(125.5±2.4)kU·L-1明显升高至(144.2±9.2)和(169.2±3.2)kU·L-1(P﹤0.01)。SI 360 mg·kg-1组与120 mg·kg-1组比较,SCr,BUN 及 mDA 水平显著降低(P﹤0.05,P﹤0.01),SOD 水平显著升高(P﹤0.01)。与正常对照组相比,模型组肾组织 nephrin 蛋白表达显著降低(P﹤0.01),TNF-α表达显著升高(P﹤0.01);与模型对照组相比,SI 40,120和360 mg·kg-1组 nephrin 蛋白表达明显升高( P ﹤0.01),SI 120和360 mg·kg-1组 TNF-α及 NF-κB 表达明显降低(P﹤0.01)。结论 SI 治疗糖尿病肾病的作用机制可能部分与其抗炎、抗氧化及增加 nephrin 表达有关。
目的:觀察大豆異黃酮(SI)對糖尿病大鼠腎組織 nephrin 錶達的影響,探討其對糖尿病腎病治療作用的機製。方法健康 SD 大鼠一次性尾靜脈註射鏈佐星60 mg·kg-1製備糖尿病大鼠模型,72 h 後分彆 ig 給予 SI 40,120和360 mg·kg-1,每天1次,連續8週。8週後,血糖儀檢測空腹血糖(FBG)水平;ELISA 法檢測24 h 尿蛋白(UP);全自動生化分析儀檢測血肌酐(SCr)、尿素氮(BUN)、丙二醛(mDA)和超氧化物歧化酶(SOD)含量;Western 蛋白質印跡法檢測腎組織 nephrin、腫瘤壞死因子α(TNF-α)及 NF-κB蛋白錶達。結果與正常對照組相比,糖尿病模型對照組 FBG,24 h UP,BUN,SCr 及 mDA 均明顯升高(P﹤0.05,P﹤0.01),SOD 水平明顯降低(P﹤0.01)。與模型對照組相比,SI 40,120和360 mg·kg-1組BUN 水平明顯降低( P ﹤0.05,P ﹤0.01),由(24.3±6.3)mmoI·L-1分彆降至16.8±4.9,13.4±5.4和(7.7±1.2)mmoI·L-1;SI 360 mg·kg-1組24 h UP 由(1.26±0.45)mg 顯著降低至(0.88±0.15)mg( P﹤0.01),SCr 由(56.4±8.4)μmoI·L-1顯著降低至(35.3±4.3)μmoI·L-1( P ﹤0.01),mDA 水平由(8.32±1.40)μmoI·L-1顯著降低至(5.33±0.95)μmoI·L-1( P ﹤0.01);SI 120和360 mg·kg-1組 SOD 水平由(125.5±2.4)kU·L-1明顯升高至(144.2±9.2)和(169.2±3.2)kU·L-1(P﹤0.01)。SI 360 mg·kg-1組與120 mg·kg-1組比較,SCr,BUN 及 mDA 水平顯著降低(P﹤0.05,P﹤0.01),SOD 水平顯著升高(P﹤0.01)。與正常對照組相比,模型組腎組織 nephrin 蛋白錶達顯著降低(P﹤0.01),TNF-α錶達顯著升高(P﹤0.01);與模型對照組相比,SI 40,120和360 mg·kg-1組 nephrin 蛋白錶達明顯升高( P ﹤0.01),SI 120和360 mg·kg-1組 TNF-α及 NF-κB 錶達明顯降低(P﹤0.01)。結論 SI 治療糖尿病腎病的作用機製可能部分與其抗炎、抗氧化及增加 nephrin 錶達有關。
목적:관찰대두이황동(SI)대당뇨병대서신조직 nephrin 표체적영향,탐토기대당뇨병신병치료작용적궤제。방법건강 SD 대서일차성미정맥주사련좌성60 mg·kg-1제비당뇨병대서모형,72 h 후분별 ig 급여 SI 40,120화360 mg·kg-1,매천1차,련속8주。8주후,혈당의검측공복혈당(FBG)수평;ELISA 법검측24 h 뇨단백(UP);전자동생화분석의검측혈기항(SCr)、뇨소담(BUN)、병이철(mDA)화초양화물기화매(SOD)함량;Western 단백질인적법검측신조직 nephrin、종류배사인자α(TNF-α)급 NF-κB단백표체。결과여정상대조조상비,당뇨병모형대조조 FBG,24 h UP,BUN,SCr 급 mDA 균명현승고(P﹤0.05,P﹤0.01),SOD 수평명현강저(P﹤0.01)。여모형대조조상비,SI 40,120화360 mg·kg-1조BUN 수평명현강저( P ﹤0.05,P ﹤0.01),유(24.3±6.3)mmoI·L-1분별강지16.8±4.9,13.4±5.4화(7.7±1.2)mmoI·L-1;SI 360 mg·kg-1조24 h UP 유(1.26±0.45)mg 현저강저지(0.88±0.15)mg( P﹤0.01),SCr 유(56.4±8.4)μmoI·L-1현저강저지(35.3±4.3)μmoI·L-1( P ﹤0.01),mDA 수평유(8.32±1.40)μmoI·L-1현저강저지(5.33±0.95)μmoI·L-1( P ﹤0.01);SI 120화360 mg·kg-1조 SOD 수평유(125.5±2.4)kU·L-1명현승고지(144.2±9.2)화(169.2±3.2)kU·L-1(P﹤0.01)。SI 360 mg·kg-1조여120 mg·kg-1조비교,SCr,BUN 급 mDA 수평현저강저(P﹤0.05,P﹤0.01),SOD 수평현저승고(P﹤0.01)。여정상대조조상비,모형조신조직 nephrin 단백표체현저강저(P﹤0.01),TNF-α표체현저승고(P﹤0.01);여모형대조조상비,SI 40,120화360 mg·kg-1조 nephrin 단백표체명현승고( P ﹤0.01),SI 120화360 mg·kg-1조 TNF-α급 NF-κB 표체명현강저(P﹤0.01)。결론 SI 치료당뇨병신병적작용궤제가능부분여기항염、항양화급증가 nephrin 표체유관。
OBJECTlVE To observe the effect of soybean isofIavone( SI)on the expression of nephrin and investigate its protection mechanism in the kidney of diabetic rats. METHODS A diabetic rat modeI was induced after streptozocin(STZ)60 mg·kg-1 was injected into Sprague-DawIey rats. After 72 h,SI 40,120 and 360 mg·kg-1 was ip given to rats in SI groups,respectiveIy,once daiIy,for 8 weeks. The concentration of fasting bIood gIucose( FBG)was determined by a bIood gIucose meter. Urine protein(UP)of 24 h was determined using ELISA. The concentration of serum creatinine(SCr),bIood urea nitrogen(BUN),maIondiaIdehyde(mDA)and superoxide dismutase(SOD)was determined by an automatic biochemicaI anaIyzer. The expression of nephrin,tumor necrosis factor-α(TNF-α)and NF-κB protein in renaI tissue was measured by Western bIotting,respectiveIy. RESULTS Compared with normaI controI group,the concentration of FBG,24 h UP,BUN,SCr and mDA in modeI group was aII siginificantIy increased(P﹤0.05,P﹤0.01),but SOD was decreased( P﹤0.01).Compared with modeI group,BUN in SI 40,120 and 360 mg·kg-1 groups decreased from(24.3±6.3)mmoI·L-1 to(16.8±4.9), (13.4±5.4)and(7.7±1.2)mmoI·L-1 ,respectiveIy,24 h UP in SI 360 mg·kg-1 group decreased from (1.26±0.45)mg to(0.88±0.15)mg( P﹤0.01),SCr decreased from(56.4±8.4)μmoI·L-1 to(35.3± 4.3)μmoI·L-1(P﹤0.01),mDA decreased from(8.32±1.40)μmoI·L-1 to(5.33±0.95)μmoI·L-1(P﹤0.01), but SOD in SI 120 and 360 mg·kg-1 groups increased from(125.5 ±2.4)kU·L-1 to 144.2 ±9.2 and (169.2±3.2)kU·L-1(P﹤0.01). Compared with SI 120 mg·kg-1 ,SCr,BUN and mDA in SI 360 mg·kg-1 group were aII siginificantIy Iower(P﹤0.05,P﹤0.01),but SOD was higher(P﹤0.01). Compared with normaI controI group,the expression of nephrin protein greatIy decreased(P﹤0.01),whiIe the expres-sion of TNF-α protein greatIy increased in modeI group( P ﹤0.01). Compared with modeI group,the expression of nephrin protein greatIy increased in SI 40,120 and 360 mg·kg-1 groups(P﹤0.01),whiIe the expression of TNF-α and NF-κB protein greatIy decreased in SI 120 and 360 mg·kg-1 groups(P﹤0.01). CONCLUSlON The mechanism by which SI protects the kidney may be partIy reIated to anti-infIammation,antioxidation and increasing the expression of nephrin in diabetic rats.