中国医师杂志
中國醫師雜誌
중국의사잡지
JOURNAL OF CHINESE PHYSICIAN
2010年
7期
903-906
,共4页
李华%许传文%吴扬%徐艳梅%吴伟聪%黄杰
李華%許傳文%吳颺%徐豔梅%吳偉聰%黃傑
리화%허전문%오양%서염매%오위총%황걸
四唑类/药理学%联苯化合物/药理学%糖尿病/药物疗法/病理学/代谢%前列腺素内过氧化物合酶类/代谢%肾/代谢
四唑類/藥理學%聯苯化閤物/藥理學%糖尿病/藥物療法/病理學/代謝%前列腺素內過氧化物閤酶類/代謝%腎/代謝
사서류/약이학%련분화합물/약이학%당뇨병/약물요법/병이학/대사%전렬선소내과양화물합매류/대사%신/대사
Tetrazoles/PD%Biphenyl compounds/PD%Diabetes mellitus/DT/PA/ME%Prostaglandin-endoperoxide synthases/ME%Kidney/ME
目的 探讨血管紧张素Ⅱ(AngⅡ)1型受体拮抗剂(ARB)厄贝沙坦对2型糖尿病大鼠肾组织环氧化酶-2(COX-2)表达的影响及其肾保护的可能机制.方法 将18只实验大鼠随机分成正常对照组(A组)、糖尿病组(B组)、厄贝沙坦治疗组(C组).6周时用免疫组织化学法检测肾脏COX-2、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制物1(TIMP-1)表达,并采用放射免疫法测定尿液前列腺素代谢产物血栓烷素B2(TXB2)、6-酮前列腺素F1α(6-Ket-PGF1α)排泄量.结果 与A组比较,B组大鼠肾脏COX-2、TIMP-1表达明显增强,MMP-9表达减弱(COX-2:0.39±0.02 vs 0.24±0.04,TIMP:0.41±0.03 vs 0.24±0.02,MMP-9:0.24±0.02 vs 0.32±0.02,P＜0.05);与B组比较,C组COX-2(0.31±0.03)、TIMP-1(0.34±0.02)表达减弱、而MMP-9(0.29±0.03)表达增强(P＜0.05);B组大鼠尿TXB2[(1313.10±14.03)ng/d]、6-Ket-PGF1α[(1598.00±39.25)ng/d]排泄量明显增加;C组尿TXB2[(658±13.68)ng/d]、6-Ket-PGF1α[(1022±58.04)ng/d]排泄量则较B组明显下降;B组大鼠出现明显蛋白尿及基底膜增厚、系膜外基质增多等病理变化;C组则无明显蛋白尿且病理变化较B组明显减弱.结论 COX-2参与了糖尿病肾病发生、发展病理过程;厄贝沙坦抑制COX-2活性、上调MMP-9、下调TIMP-1是其肾保护的可能机制之一.
目的 探討血管緊張素Ⅱ(AngⅡ)1型受體拮抗劑(ARB)阨貝沙坦對2型糖尿病大鼠腎組織環氧化酶-2(COX-2)錶達的影響及其腎保護的可能機製.方法 將18隻實驗大鼠隨機分成正常對照組(A組)、糖尿病組(B組)、阨貝沙坦治療組(C組).6週時用免疫組織化學法檢測腎髒COX-2、基質金屬蛋白酶-9(MMP-9)、基質金屬蛋白酶組織抑製物1(TIMP-1)錶達,併採用放射免疫法測定尿液前列腺素代謝產物血栓烷素B2(TXB2)、6-酮前列腺素F1α(6-Ket-PGF1α)排洩量.結果 與A組比較,B組大鼠腎髒COX-2、TIMP-1錶達明顯增彊,MMP-9錶達減弱(COX-2:0.39±0.02 vs 0.24±0.04,TIMP:0.41±0.03 vs 0.24±0.02,MMP-9:0.24±0.02 vs 0.32±0.02,P＜0.05);與B組比較,C組COX-2(0.31±0.03)、TIMP-1(0.34±0.02)錶達減弱、而MMP-9(0.29±0.03)錶達增彊(P＜0.05);B組大鼠尿TXB2[(1313.10±14.03)ng/d]、6-Ket-PGF1α[(1598.00±39.25)ng/d]排洩量明顯增加;C組尿TXB2[(658±13.68)ng/d]、6-Ket-PGF1α[(1022±58.04)ng/d]排洩量則較B組明顯下降;B組大鼠齣現明顯蛋白尿及基底膜增厚、繫膜外基質增多等病理變化;C組則無明顯蛋白尿且病理變化較B組明顯減弱.結論 COX-2參與瞭糖尿病腎病髮生、髮展病理過程;阨貝沙坦抑製COX-2活性、上調MMP-9、下調TIMP-1是其腎保護的可能機製之一.
목적 탐토혈관긴장소Ⅱ(AngⅡ)1형수체길항제(ARB)액패사탄대2형당뇨병대서신조직배양화매-2(COX-2)표체적영향급기신보호적가능궤제.방법 장18지실험대서수궤분성정상대조조(A조)、당뇨병조(B조)、액패사탄치료조(C조).6주시용면역조직화학법검측신장COX-2、기질금속단백매-9(MMP-9)、기질금속단백매조직억제물1(TIMP-1)표체,병채용방사면역법측정뇨액전렬선소대사산물혈전완소B2(TXB2)、6-동전렬선소F1α(6-Ket-PGF1α)배설량.결과 여A조비교,B조대서신장COX-2、TIMP-1표체명현증강,MMP-9표체감약(COX-2:0.39±0.02 vs 0.24±0.04,TIMP:0.41±0.03 vs 0.24±0.02,MMP-9:0.24±0.02 vs 0.32±0.02,P＜0.05);여B조비교,C조COX-2(0.31±0.03)、TIMP-1(0.34±0.02)표체감약、이MMP-9(0.29±0.03)표체증강(P＜0.05);B조대서뇨TXB2[(1313.10±14.03)ng/d]、6-Ket-PGF1α[(1598.00±39.25)ng/d]배설량명현증가;C조뇨TXB2[(658±13.68)ng/d]、6-Ket-PGF1α[(1022±58.04)ng/d]배설량칙교B조명현하강;B조대서출현명현단백뇨급기저막증후、계막외기질증다등병리변화;C조칙무명현단백뇨차병리변화교B조명현감약.결론 COX-2삼여료당뇨병신병발생、발전병리과정;액패사탄억제COX-2활성、상조MMP-9、하조TIMP-1시기신보호적가능궤제지일.
Objective To investigate the effect of angiotensin Ⅱ (AngⅡ) type 1 receptor block irbesartan on the expression of renal cyclooxygenase-2 ( COX-2 ) in rats with type 2 diabetes mellitus.Methods 18 rats were divided into control group, diabetes mellitus group and treating group.Immunohistochemistry was used to measure the expression of COX-2, matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1).The urinary TXB2,6-Ket-PGF1 αconcentration was determined by radioimmunoassay at the 6th week .Results There was an increasing expression of COX-2,TIMP-1 and decreasing M MP-9 ( COX-2:0.39 ± 0.02 vs 0.24 ± 0.04, TIMP :0.41 ± 0.03 vs 0.24 ± 0.02,MMP-9:0.24 ± 0.02 vs 0.32 ± 0.02, P ＜ 0.05 ) expression in the diabetes mellitus group ( P ＜ 0.05 ).Irbesartan could increase MMP-9 (0.29 ± 0.03 ) and depress TIMP-1 (0.34 ± 0.02) expression through inhibiting the expression of COX-2(0.31 ± 0.03) in renal tissue.Conclusions COX-2 was involved in the pathogenesis of the injury of type 2 diabetic nephropathy.Irbesartan might exert its renoprotective effects through inhibiting COX-2 activity, modulating the expression of MMP-9 and TIMP-1.
