CAJ | 학술논문

目的探讨依那普利和波生坦对糖尿病肾病(DN)的治疗作用. 方法 Wistar大鼠摘除右肾后,静脉注射链脲佐菌素致成糖尿病模型鼠,分为4组:糖尿病模型(Veh)组(给缓冲液);波生坦干预(Bos)组(100 mg*kg-1*d-1);依那普利干预(Ena)组(10 mg*kg-1*d-1);波生坦及依那普利联合干预(Bos+Ena)组(两药剂量同上).尚设单肾对照组(静脉注射缓冲液).每组大鼠6只.20周时测量体重、血压、血糖及24 h尿蛋白定量,处死大鼠,取左肾称重,用 RT-PCR及免疫组化法检测肾组织中Ⅰ型胶原(CⅠ)、Ⅳ型胶原(C Ⅳ)、转化生长因子-β1(TGF-β1)、纤溶酶原激活剂抑制物-1(PAI-1)及金属蛋白酶组织抑制物-1(TIMP-1)的mRNA及蛋白质表达. 结果与对照组相比,Veh组大鼠平均动脉压、血糖、尿蛋白定量及肾重/体重比值均显著上升(P<0.05),肾组织的CⅠ、C Ⅳ、TGF-β1、PAI-1及TIMP-1的mRNA及蛋白质表达均显著上调(P<0.05).Bos、Ena及两药联合治疗后,上述上调指标除血糖外均显著抑制(P<0.05),而3组间抑制率差异无显著意义(P>0.05). 结论无论非选择性内皮素-1受体拮抗剂Bos或血管紧张素转换酶抑制剂Ena,对DN均具有肯定疗效;两药可能通过下调肾组织中TGF-β1、PAI-1及TIMP-1表达,而使CⅠ及C Ⅳ生成减少而发挥疗效.
목적 탐토의나보리화파생탄대당뇨병신병(DN)적치료작용. 방법 Wistar대서적제우신후,정맥주사련뇨좌균소치성당뇨병모형서,분위4조:당뇨병모형(Veh)조(급완충액);파생탄간예(Bos)조(100 mg*kg-1*d-1);의나보리간예(Ena)조(10 mg*kg-1*d-1);파생탄급의나보리연합간예(Bos+Ena)조(량약제량동상).상설단신대조조(정맥주사완충액).매조대서6지.20주시측량체중、혈압、혈당급24 h뇨단백정량,처사대서,취좌신칭중,용 RT-PCR급면역조화법검측신조직중Ⅰ형효원(CⅠ)、Ⅳ형효원(C Ⅳ)、전화생장인자-β1(TGF-β1)、섬용매원격활제억제물-1(PAI-1)급금속단백매조직억제물-1(TIMP-1)적mRNA급단백질표체. 결과여대조조상비,Veh조대서평균동맥압、혈당、뇨단백정량급신중/체중비치균현저상승(P<0.05),신조직적CⅠ、C Ⅳ、TGF-β1、PAI-1급TIMP-1적mRNA급단백질표체균현저상조(P<0.05).Bos、Ena급량약연합치료후,상술상조지표제혈당외균현저억제(P<0.05),이3조간억제솔차이무현저의의(P>0.05). 결론무론비선택성내피소-1수체길항제Bos혹혈관긴장소전환매억제제Ena,대DN균구유긍정료효;량약가능통과하조신조직중TGF-β1、PAI-1급TIMP-1표체,이사CⅠ급C Ⅳ생성감소이발휘료효.
Objective To investigate the pathogenesis and intervention measures of diabetic nephropathy Methods Uninephrectomized Wistar rats were given intravenously streptozotocin (STZ) The diabetic rats were randomly divided into four groups by gavage: Veh group (only buffer); Bos group (bosentan 100 mg/kg/d); Ena group (enalapril 10 mg/kg/d); Bos+Ena group (the same doses of both bosentan and enalapril) Besides, uninephrectomized rats without STZ injection were assigned as control group Each group consisted of 6 rats By twenty weeks, the body weight, blood pressure, blood glucose and proteinuria were measured in each group Then, the rats were sacrificed and the remnant kidney of each rat was harvested and weighed respectively The mRNA and the protein expression of collagen Ⅰ(C Ⅰ),collagen Ⅳ (C Ⅳ),transforming growth factor β 1 (TGF β 1),plasminogen activator inhibitor 1 (PAI 1), tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in kidney tissue were semi quantitatively detected with reverse transcription polymerase chain reaction (RT PCR) and immunohistochemical staining respectively Results In Veh group the mean arterial pressure (MAP), blood glucose level, urinary protein excretion, and the ratio of kidney weight/body weight were significantly increased compared with control group ( P <0 05), and the expression of C Ⅰ,C Ⅳ,TGF β 1,PAI 1 and TIMP 1 mRNA and protein in kidney tissue was also significantly up regulated compared with control group (P <0 05) In three treatment groups the increased above mentioned parameters except blood glucose were significantly attenuated compared with Veh group ( P <0 05), but there were no significant differences in the parameters among these three groups ( P >0 05) Conclusions Either endothelin receptor antagonist bosentan or ACE inhibitor enalapril has definite therapeutic effects on diabetic nephropathy These effects might come from the decreased C Ⅰand C Ⅳproduction in the diabetic kidney tissue resulted from the down regulation of TGF β 1, PAI 1 and TIMP 1 expression by bosentan or/and enalapril